Epidural spinal cord stimulation as an intervention for motor recovery after motor complete spinal cord injury

Spinal cord injury (SCI) commonly results in permanent loss of motor, sensory, and autonomic function. Recent clinical studies have shown that epidural spinal cord stimulation may provide a beneficial adjunct for restoring lower extremity and other neurological functions. Herein, we review the recent clinical advances of lumbosacral epidural stimulation for restoration of sensorimotor function in individuals with motor complete SCI and we discuss the putative neural pathways involved in this promising neurorehabilitative approach. We focus on three main sections: review recent clinical results for locomotor restoration in complete SCI; discuss the contemporary understanding of electrical neuromodulation and signal transduction pathways involved in spinal locomotor networks; review current challenges of motor system modulation and future directions towards integrative neurorestoration. The current understanding is that initial depolarization occurs at the level of large diameter dorsal root proprioceptive afferents that when integrated with interneuronal and latent residual supraspinal translesional connections can recruit locomotor centers and augment downstream motor units. Spinal epidural stimulation can initiate excitability changes in spinal networks and supraspinal networks. Different stimulation parameters can facilitate standing or stepping, and it may also have potential for augmenting myriad other sensorimotor and autonomic functions. More comprehensive investigation of the mechanisms that mediate the transformation of dysfunctional spinal networks to higher functional states with a greater focus on integrated systems based control system may reveal the key mechanisms underlying neurological augmentation and motor restoration after severe paralysis.

First experience with chronic epidural spinal cord stimulation in Khanty-Mansi autonomous okrug — clinical observations

Purpose of the work. The article is devoted to the first experience of epidural stimulation in the Khanty-Mansiysk Autonomous Okrug at the budgetary institution Surgut Clinical Trauma Hospital. Clinical examples are presented for two main indications for the application of this technique (disease of the operated spine, a consequence of spinal cord injury in combination with chronic neuropathic pain syndrome). Research methods. An assessment of the intensity of pain syndrome was given according to a visual analogue scale, the Pain Detect questionnaire; indicators of anxiety, depression on the HADS scale; quality of life according to the Oswestry questionnaire for a follow-up period of 6-12 months in patients with chronic epidural stimulation. Results. A positive assessment of the action during test neurostimulation was 63.3% (38 patients). Of the established permanent systems, a good result was achieved and persisted for 12 months or more in 96% (24 patients). It was necessary to change the stimulation parameters in 13% (3 patients). Revision of permanent systems was performed in 20% (5 patients), due to the progression of the degenerative-dystrophic process of the spine, damage and migration of system elements. Conclusions. Chronic epidural spinal cord stimulation has established itself as a personalized, highly effective, minimally invasive and safe method of treating chronic neuropathic pain syndromes. Multicomponent corrective action is of scientific interest and requires further study.

Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input–output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

Epidural spinal cord stimulation for motor recovery in spinal cord injury: A systematic review

BACKGROUND: Epidural spinal cord stimulation (ESCS) emerged as a technology for eliciting motor function in the 1990’s and was subsequently employed therapeutically in the spinal cord injured (SCI) population. Despite a considerable number of ESCS studies, a comprehensive systematic review of ESCS remains unpublished. OBJECTIVE: The current review of the existing literature evaluated the efficacy of ESCS for improving motor function in individuals with SCI. METHODS: A search for ESCS studies was performed using the following databases: Medline (Ovid), Web of Science and Embase. Furthermore, to maximize results, an inverse manual search of references cited by identified articles was also performed. Studies published between January 1995 and June 2020 were included. The search was constructed around the following key terms: Spinal cord stimulation, SCI and motor response generation. RESULTS: A total of 3435 articles were initially screened, of which 18 met the inclusion criteria. The total sample comprised of 24 participants with SCI. All studies reported some measure of improvement in motor activity with ESCS, with 17 reporting altered EMG responses. Functional improvements were reported in stepping (n = 11) or muscle force (n = 4). Only 5 studies assessed ASIA scale pre- and post-intervention, documenting improved classification in 4 of 11 participants. Appraisal using the modified Downs and Black quality checklist determined that reviewed studies were of poor quality. Due to heterogeneity of outcome measures utilized in studies reviewed, a meta-analysis of data was not possible. CONCLUSION: While the basic science is encouraging, the therapeutic efficacy of ESCS remains inconclusive.

High-density spinal cord stimulation selectively activates lower urinary tract afferents

Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.

Brain fMRI during orientation selective epidural spinal cord stimulation

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.