Engaging Spinal Networks to Mitigate Supraspinal Dysfunction After CP

Although children with cerebral palsy seem to have the neural networks necessary to generate most movements, they are markedly dysfunctional, largely attributable to abnormal patterns of muscle activation, often characterized as spasticity, largely reflecting a functionally abnormal spinal-supraspinal connectivity. While it is generally assumed that the etiologies of the disruptive functions associated with cerebral palsy can be attributed primarily to supraspinal networks, we propose that the more normal connectivity that persists between peripheral proprioception-cutaneous input to the spinal networks can be used to guide the reorganization of a more normal spinal-supraspinal connectivity. The level of plasticity necessary to achieve the required reorganization within and among different neural networks can be achieved with a combination of spinal neuromodulation and specific activity-dependent mechanisms. By engaging these two concepts, we hypothesize that bidirectional reorganization of proprioception-spinal cord-brain connectivity to higher levels of functionality can be achieved without invasive surgery

Transcutaneous Electrical Spinal Cord Neuromodulator (TESCoN) Improves Symptoms of Overactive Bladder

Non-Surgical modality to reduce incidence of urinary incontinence and improve neurogenic bladder symptom scores (NBSS) in individuals with neurogenic bladder due to spinal cord injury or stroke

The Effect of Non-invasive Spinal Cord Stimulation on Anorectal Function in Individuals With Spinal Cord Injury : A Case Series

Spinal cord injury (SCI) is a devastating condition that impacts multiple organ systems. Neurogenic bowel dysfunction (NBD) frequently occurs after a SCI leading to reduced sensation of bowel fullness and bowel movement often leading to constipation or fecal incontinence. Spinal Neuromodulation has been proven to be a successful modality to improve sensorimotor and autonomic function in patients with spinal cord injuries. The pilot data presented here represents the first demonstration of using spinal neuromodulation to activate the anorectal regions of patients with spinal cord injuries and the acute and chronic effects of stimulation. We observed that spinal stimulation induces contractions as well as changes in sensation and pressure profiles along the length of the anorectal region. In addition, we present a case report of a patient with a SCI and the beneficial effect of spinal neuromodulation on the patient's bowel program

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats

Background: Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. Methods: We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1–100 Hz and 1–10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. Results: In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Conclusions: Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles

A pilot study combining noninvasive spinal neuromodulation and activity-based neurorehabilitation therapy in children with cerebral palsy

Cerebral Palsy (CP) is the most common pediatric motor disability with multiple symptoms and etiologies. CP is exhibited through sensorimotor delays, impaired posture resulting in limited activities and participation. Our recently concluded, single arm, unblinded, pilot study (NCT04882592) explored whether an intervention combining non-invasive spinal neuromodulation during an activity-based neurorehabilitation therapy (ABNT) can improve voluntary sensory-motor function captured via the Gross Motor Function Measure (GMFM-88) scores (primary outcome). Sixteen children diagnosed with CP with Gross Motor Function Classification Scale levels I-V were recruited and received the same intervention (2x/week for 8 weeks) to correct the dysfunctional connectivity between supraspinal and spinal networks using the normally developed proprioception. We demonstrate that the intervention was associated with clinically and statistically significant improvement in GMFM-88 scores in all children, thus meeting the prespecified primary endpoint. However, the improvement with ABNT alone needs further exploration. No serious adverse events were observed (safety endpoint). Here the authors report a single arm pilot trial to investigate combined spinal neuromodulation and activity-based neurorehabilitation therapy on voluntary sensory-motor function in children with cerebral palsy

Noninvasive spinal neuromodulation mitigates symptoms of idiopathic overactive bladder

Altres ajuts: Academy of Finland 129164Overactive bladder (OAB) affects 12 to 30% of the world's population. The accompanying urinary urgency, frequency and incontinence can have a profound effect on quality of life, leading to depression, social isolation, avoidance of sexual activity and loss of productivity. Conservative measures such as lifestyle modification and pelvic floor physical therapy are the first line of treatment for overactive bladder. Patients who fail these may go on to take medications, undergo neuromodulation or receive injection of botulinum toxin into the bladder wall. While effective, medications have side effects and suffer from poor adherence. Neuromodulation and botulinum toxin injection are also effective but are invasive and not acceptable to some patients. We have developed a novel transcutaneous spinal cord neuromodulator (SCONE™,) that delivers multifrequency electrical stimulation to the spinal cord without the need for insertion or implantation of stimulating electrodes. Previously, multifrequency transcutaneous stimulation has been demonstrated to penetrate to the spinal cord and lead to motor activation of detrusor and external urethral sphincter muscles. Here, we report on eight patients with idiopathic overactive bladder, who underwent 12 weeks of SCONE™ therapy. All patients reported statistically significant clinical improvement in multiple symptoms of overactive bladder, such as urinary urgency, frequency and urge incontinence. In addition, patients reported significant symptomatic improvements as captured by validated clinical surveys. SCONE™ therapy represents the first of its kind therapy to treat symptoms of urgency, frequency and urge urinary incontinence in patients with OAB. The study was listed on clinicaltrials.gov ()

Neuromodulation of the neural circuits controlling the lower urinary tract

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner

An Active Learning Algorithm for Control of Epidural Electrostimulation

Epidural electrostimulation has shown promise for spinal cord injury therapy. However, finding effective stimuli on the multi-electrode stimulating arrays employed requires a laborious manual search of a vast space for each patient. Widespread clinical application of these techniques would be greatly facilitated by an autonomous, algorithmic system which choses stimuli to simultaneously deliver effective therapy and explore this space. We propose a method based on GP-BUCB, a Gaussian process bandit algorithm. In n = 4 spinally transected rats, we implant epidural electrode arrays and examine the algorithm’s performance in selecting bipolar stimuli to elicit specified muscle responses. These responses are compared with temporally interleaved intra-animal stimulus selections by a human expert. GP-BUCB successfully controlled the spinal electrostimulation preparation in 37 testing sessions, selecting 670 stimuli. These sessions included sustained autonomous operations (ten-session duration). Delivered performance with respect to the specified metric was as good as or better than that of the human expert. Despite receiving no information as to anatomically likely locations of effective stimuli, GP-BUCB also consistently discovered such a pattern. Further, GP-BUCB was able to extrapolate from previous sessions’ results to make predictions about performance in new testing sessions, while remaining sufficiently flexible to capture temporal variability. These results provide validation for applying automated stimulus selection methods to the problem of spinal cord injury therapy