Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Walking naturally after spinal cord injury using a brain-spine interface.

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis1,2. Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain-spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking4-6. A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

Activating effective functional hand movements in individuals with complete tetraplegia through neural stimulation.

Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw.

Improving Upper Extremity Strength, Function, and Trunk Stability Using Wide-Pulse Functional Electrical Stimulation in Combination With Functional Task-Specific Practice.

Objectives: To evaluate upper extremity (UE) function, strength, and dynamic sitting balance in individuals with spinal cord injury (SCI) who received an intensive outpatient therapy program focused on UE training augmented with wide pulse/high frequency functional electrical stimulation (WPHF-FES). Methods: This prospective case series was conducted in an outpatient (OP) clinic in an SCI-specific rehabilitation hospital. Participants were a convenience sample (N = 50) of individuals with tetraplegia receiving OP therapy focused on UE recovery. Individuals participated in 60 minutes of UE functional task-specific practice (FTP) in combination with WPHF-FES 5 times/week for an average of 72 sessions. The primary outcome for this analysis was the Capabilities of Upper Extremity Test (CUE-T). Secondary outcomes include UE motor score (UEMS) and the modified functional reach (MFR). Results: Fifty individuals (13 motor complete; 37 motor incomplete SCI) completed an OP UE training program incorporating WPHF-FES and were included in this analysis. On average, participants demonstrated significant improvements in the total CUE-T score of 14.1 (SD = 10.0, p < .0001) points; significant changes were also noted in UEMS and MFR, improving an average of 4.6 (SD = 5.2, p < .0001) points and 13.6 (SD = 15.8, p < .0001) cm, respectively. Conclusion: Individuals with tetraplegia demonstrated significant improvements in UE strength, function, and dynamic sitting trunk balance after receiving UE training augmented with WPHF-FES. Future comparative effectiveness studies need to be completed to guide efficacious treatment interventions in OP therapy.

Brain implant enables man in locked-in state to communicate.

Despite complete paralysis from amyotrophic lateral sclerosis, person used neural signals to spell out thoughts.

Guillain-Barre Syndrome After Two COVID-19 Vaccinations: Two Case Reports With Follow-up Electrodiagnostic Study.

Guillain-Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy and commonly occurs after a preceding infection or immunization sequalae. Following the severe acute respiratory syndrome-coronavirus-2 virus pandemic with co-introduction of massive vaccinations, several GBS cases associated with coronavirus disease 2019 (COVID-19) infection per se or after vaccination for COVID-19 were reported internationally. Herein, we report two cases of Korean GBS presenting with tetraplegia after two different COVID-19 vaccinations (42-year old man by AstraZeneca and 48-year woman by Pfizer vaccines) within four weeks after vaccination. The patients were diagnosed with clinical examination, serial electromyography, and compatible laboratory results and improved after comprehensive rehabilitative treatment and intravenous immunoglobulin therapy. Furthermore, we performed an electrodiagnostic follow-up study of each case to examine their unique characteristics.

Epidural stimulation with locomotor training ameliorates unstable blood pressure after tetraplegia. A case report.

A male with C7 complete tetraplegia participated in 14 weeks of body weight supported treadmill training (BWSTT) combined with spinal cord epidural stimulation (SCES), 4 weeks of no intervention, and two more weeks of BWSTT + SCES. The participant presented with unstable resting seated blood pressure (BP; 131/66 mmHg). After retrospective analysis, resting systolic BP decreased and diastolic BP increased, yielding a safe mean arterial BP. There was a fivefold increase in BWSTT bouts per session, and percentage of body weight support decreased to 69%. BWSTT + SCES safely and effectively regulated resting BP and mitigated symptoms of orthostatic intolerance. These effects were not maintained after 4 weeks without training.

Electrical stimulation alters muscle morphological properties in denervated upper limb muscles.

BACKGROUND: Damage to lower motor neuron causes denervation and degeneration of the muscles affected. Experimental and clinical studies of muscle denervation in lower extremities demonstrated that direct electrical stimulation (ES) of muscle can prevent denervation atrophy and restore contractility. The aim of this study was to identify possible myogenic effect of ES on denervated forearm and hand muscles in persons with spinal cord injury (SCI) and tetraplegia. METHODS: This prospective interventional study with repeated measurement design included 22 patients aged 48·6 (± 15·7), 0·25 (0·1/46) years after spinal cord lesion, AIS A-D. In each patient, two electrophysiologically-confirmed denervated muscles in the hand and forearm were analyzed - one extrinsic (Extensor Carpi Ulnaris - ECU) and one intrinsic (1st Dorsal Interosseus - IOD1). Muscles were stimulated for 33 min, five times per week over a 12-weeks period. Using ultrasonography (USG), muscle thickness (MT) and pennation angle (PA) of these muscles were determined at start and end of the stimulation period. FINDINGS: MT of IOD1 increased from 6·3 mm (± 3·2 mm) to 9·2 mm (± 2·4 mm) (p = 0·004) and the PA from 5·5° (± 3·0°) to 11° (± 2·2°) (p = 0·001). The corresponding values for the ECU were 5·5 mm (± 2·5 mm) to 7·0 mm (± 2·2 mm) (p = 0·039) and 5·5° (± 3·4°) to 9·4° (± 3·8°) (p = 0·005), respectively. The correlation of MT between baseline and completion was r = 0·58 (p = 0·037) for the ECU and r = 0·63 (p = 0·008) for the IOD1. INTERPRETATION: 12 weeks of direct muscle stimulation increases the MT and PA of the denervated intrinsic and extrinsic hand muscles studied. FUNDING: Swiss Paraplegic Centre, Switzerland.

Transient Quadriparesis and Cervical Neuropraxia in Elite Athletes.

Elite athletes are often faced with difficult decisions when faced with a cervical spinal disorder. There are many aspects to consider such as the risk of further injury, short- and long-term effects on an athlete's life both during and after his/her career, and the options for treatment. Although there have been some recent contributions to this topic, the evidence-based literature is generally devoid of high-level clinical studies to help guide the decision-making process. This article reviews the pertinent available data/criteria and offer an algorithm for return-to-play considerations.

A brain-computer interface that evokes tactile sensations improves robotic arm control.

Prosthetic arms controlled by a brain-computer interface can enable people with tetraplegia to perform functional movements. However, vision provides limited feedback because information about grasping objects is best relayed through tactile feedback. We supplemented vision with tactile percepts evoked using a bidirectional brain-computer interface that records neural activity from the motor cortex and generates tactile sensations through intracortical microstimulation of the somatosensory cortex. This enabled a person with tetraplegia to substantially improve performance with a robotic limb; trial times on a clinical upper-limb assessment were reduced by half, from a median time of 20.9 to 10.2 seconds. Faster times were primarily due to less time spent attempting to grasp objects, revealing that mimicking known biological control principles results in task performance that is closer to able-bodied human abilities.

Beware the Wandering Needle: Inadvertent Intramedullary Injection During an Attempted Cervical Medial Branch Block.

A 27-year-old man developed sudden neck pain, severe quadriparesis, and right shoulder allodynia during an outpatient cervical medial branch block procedure. Cervical spine imaging revealed evidence of an interlaminar needle trajectory with abnormal signal in the right hemicord at the level of C4, consistent with intramedullary injection and contusion. Following a 48-hour stay in the intensive care unit, during which hemodynamic vasopressor support was administered to optimize spinal cord perfusion, the patient exhibited almost complete neurologic recovery with resolution of the neuropathic pain. He was eventually discharged home and underwent outpatient physical therapy for a mild residual right hemiparesis.

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia.

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI. During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1-2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O2) and room air (1 min episodes of 20.9% O2). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.

Active proportional electromyogram controlled functional electrical stimulation system.

Neurophysiological theories and past studies suggest that intention driven functional electrical stimulation (FES) could be effective in motor neurorehabilitation. Proportional control of FES using voluntary EMG may be used for this purpose. Electrical artefact contamination of voluntary electromyogram (EMG) during FES application makes the technique difficult to implement. Previous attempts to date either poorly extract the voluntary EMG from the artefacts, require a special hardware or are unsuitable for online application. Here we show an implementation of an entirely software-based solution that resolves the current problems in real-time using an adaptive filtering technique with an optional comb filter to extract voluntary EMG from muscles under FES. We demonstrated that unlike the classic comb filter approach, the signal extracted with the present technique was coherent with its noise-free version. Active FES, the resulting EMG-FES system was validated in a typical use case among fifteen patients with tetraplegia. Results showed that FES intensity modulated by the Active FES system was proportional to intentional movement. The Active FES system may inspire further research in neurorehabilitation and assistive technology.

Caring for Patients with Spinal Cord Injuries.

The column in this issue is supplied by Juan Jose Olivero, MD, who was a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program before his retirement in 2019. Dr. Olivero obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas. He currently serves on the journal's editorial board and is editor of the "Points to Remember" section.

A case for inspiratory muscle training in SCI: potential role as a preventative tool in infectious respiratory diseases like COVID-19.

INTRODUCTION: Respiratory complications (RC) are a leading cause of death after spinal cord injury (SCI) due to compromised immune function and respiratory muscle weakness. Thus, individuals with SCI are at high risk of developing COVID-19 related RC. Results of a SCI clinical trial showed a supervised respiratory muscle training (RMT) program decreased risk of developing RC. The feasibility of conducting unsupervised RMT is not well documented. Four publications (n = 117) were identified in which unsupervised RMT was performed. Significant improvements in respiratory outcomes were reported in two studies: Maximal Inspiratory and Expiratory Pressure (MIP40% and MEP25%, respectively), Peak Expiratory Flow (PEF9%), seated and supine Forced Vital Capacity (FVC23% and 26%, respectively), and Peak Cough Flow (28%). This review and case report will attempt to show that an inspiratory muscle training (IMT) home exercise program (HEP) is feasible and may prepare the respiratory system for RC associated with COVID-19 in patients with SCI. CASE PRESENTATION: A 23-year-old with tetraplegia (P1), history of mechanical ventilation, and hospitalization for RC, completed 27 IMT HEP sessions in one month. MIP and sustained MIP (SMIP) increased from baseline by 28% and 26.5%, respectively. Expiratory volumes and rates also improved (FVC, FEV1, and PEF: 11.7%, 8.3%, and 14.2%, respectively). DISCUSSION: The effects of COVID-19 on patients with SCI remains inconclusive, but recent literature and the results of this case suggest that unsupervised IMT is feasible and may limit the severity of RC in patients with SCI who contract COVID-19.

Feasibility and safety of 4 weeks of blood flow-restricted exercise in an individual with tetraplegia and known autonomic dysreflexia: a case report.

INTRODUCTION: Blood flow-restricted exercise (BFRE) appears to hold considerable potential in spinal cord injury (SCI) rehabilitation, due to its ability to induce beneficial functional changes and morphological alterations from low-intensity, low-load exercise. However, it remains unclear if this training approach is feasible and safe in individuals with autonomic dysreflexia (AD). CASE PRESENTATION: A 23-year-old male with traumatic, cervical (C6), motor-complete (AIS: B) SCI and diagnosed AD completed eight sessions of BFRE for the upper extremities over 4 weeks. Blood pressure and heart rate recordings and perceptual pain responses were collected repeatedly during exercise. Blood samples were drawn pre- and post-training. Training was carried out in a neurorehabilitation hospital setting with appertaining medical staff readiness, and was supervised by a physiotherapist with expertise in AD in general as well as prior knowledge of the present patient's triggers and symptoms. Four incidences of AD (defined as systolic blood pressure increase >20 mmHg) were recorded across all training sessions, of which one was symptomatic. The patient's blood profile did not change considerably from pre- to post-training sessions. Self-reported average pain during training corresponded from "mild" to "moderate". DISCUSSION: The patient was able to perform 4 weeks of BFRE, but encountered episodes of AD. Similarly, two AD episodes were registered during a single conventional, free-flow resistance training session. Evidence from clinically controlled safety studies is needed in order to establish if and how BFRE can be applied in a rehabilitation strategy in SCI individuals with neurological level of injury at or above T6 level.

Enabling respiratory control after severe chronic tetraplegia: an exploratory case study.

Respiratory dysfunction is one of the most debilitating effects of spinal cord injury (SCI) impacting the quality of life of patients and caregivers. In addition, breathing difficulties impact the rehabilitation routine a patient may potentially undergo. Transcutaneous electrical spinal cord neuromodulation (TESCoN) is a novel approach to reactivate and retrain spinal circuits after paralysis. We demonstrate that acute and chronic TESCoN therapy over the cervical spinal cord positively impacts the breathing and coughing ability in a patient with chronic tetraplegia. ln addition, we show that the improved breathing and coughing ability are not only observed in the presence of TESCoN but persisted for a few days after TESCoN was stopped.NEW & NOTEWORTHY Noninvasive spinal neuromodulation improves breathing and coughing in a patient with severe and complete tetraplegia.