Background. Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual’s daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less “automatic” than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Objective. Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Methods and Results. Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation. Conclusions. The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention.

Advancing electronics to interact with tissue necessitates meeting material constraints in electrochemical, electrical, and mechanical domains simultaneously. Clinical bioelectrodes with established electrochemical functionalities are rigid and mechanically mismatched with tissue. Whereas conductive materials with tissue-like softness and stretchability are demonstrated, when applied to electrochemically probe tissue, their performance is distorted by strain and corrosion. We devise a layered architectural composite design that couples strain-induced cracked films with a strain-isolated out-of-plane conductive pathway and in-plane nanowire networks to eliminate strain effects on device electrochemical performance. Accordingly, we developed a library of stretchable, highly conductive, and strain-insensitive bioelectrodes featuring clinically established brittle interfacial materials (iridium-oxide, gold, platinum, and carbon). We paired these bioelectrodes with different electrochemical probing methods (amperometry, voltammetry, and potentiometry) and demonstrated strain-insensitive sensing of multiple biomarkers and in vivo neuromodulation.

The combined effects of cervical electrical stimulation alone or in combination with the monoaminergic agonist buspirone on upper limb motor function were determined in six subjects with motor complete (AIS B) injury at C5 or above and more than one year from time of injury. Voluntary upper limb function was evaluated through measures of controlled hand contraction, handgrip force production, dexterity measures, and validated clinical assessment batteries. Repeated measure analysis of variance was used to evaluate functional metrics, EMG amplitude, and changes in mean grip strength. In aggregate, mean hand strength increased by greater than 300% with transcutaneous electrical stimulation and buspirone while a corresponding clinically significant improvement was observed in upper extremity motor scores and the action research arm test. Some functional improvements persisted for an extended period after the study interventions were discontinued. We demonstrate that, with these novel interventions, cervical spinal circuitry can be neuromodulated to improve volitional control of hand function in tetraplegic subjects. The potential impact of these findings on individuals with upper limb paralysis could be dramatic functionally, psychologically, and economically.

Object: Reported complications of recombinant human bone morphogenetic protein–2 (rhBMP-2) use in anterior cervical discectomy and fusion (ACDF) cases include dysphagia and cervical swelling. However, dysphagia often occurs after multilevel ACDF procedures performed with allograft (without BMP) as well. To date, there has been no large study comparing the dysphagia rates of patients who have undergone multilevel ACDF using allograft spacers with those who underwent ACDF using polyetheretherketone (PEEK) cages filled with rhBMP2. The authors report one of the first such comparisons between these 2 patient cohorts. Methods: The authors retrospectively reviewed 150 patient records. Group 1 (BMP group) consisted of 100 patients who underwent multilevel ACDF with PEEK cages filled with rhBMP-2 and instrumented with a cervical plate. Group 2 (allograft group) included a matched control cohort of 50 patients who underwent multilevel ACDF with allograft spacers and anterior plate fixation (without rhBMP-2). Patient demographics were not significantly different between the groups. Fusion was assessed by means of dynamic radiographs and/or CT at routine intervals. Complications, dysphagia incidence, standardized dysphagia score, Nurick grades, and fusion rates were assessed. Results: The mean follow-up for the BMP group (Group 1) was 35 months while the mean follow-up for the allograft group (Group 2) was 25 months. There was a complication rate of 13% in the BMP group compared with 8% in the allograft group (p < 0.005). There was no significant difference in overall dysphagia incidence between the BMP group and the allograft group (40% vs 44%, respectively; p > 0.05). However, there was a significant difference in the severity of dysphagia (using the SWAL-QOL dysphagia scoring system) between the 2 groups: 0.757 for the BMP group versus 0.596 for the allograft group (p < 0.005). In subgroup analysis, the use of rhBMP-2 significantly increased the severity of dysphagia in patients undergoing 2-level ACDF (p < 0.005). However, the severity of dysphagia did not differ significantly between groups when 3- or 4-level ACDF cases were compared. There was no pseudarthrosis in Group 1 (the BMP group) compared with a 16% pseudarthrosis rate in Group 2 (the allograft group) (p < 0.05). There was a weak correlation between the total rhBMP-2 dose and the dysphagia score (Kendall tau rank correlation coefficient 0.166, p = 0.046). Conclusions: The use of rhBMP-2 in patients undergoing 2-level ACDF significantly increases the severity of dysphagia (dysphagia score) without affecting the overall incidence of dysphagia. However, there is no statistically significant difference in the incidence or severity of dysphagia between patients undergoing 3-level or 4-level ACDF treated with PEEK/rhBMP-2 and those treated with only allograft. The use of rhBMP-2 appears to reduce the risk of pseudarthrosis. This benefit is most pronounced in patients who undergo 4-level ACDF and are smokers.

Patients with chronic spinal cord injury (SCI) cannot urinate at will and must empty the bladder by self-catheterization. We tested the hypothesis that non-invasive, transcutaneous magnetic spinal cord stimulation (TMSCS) would improve bladder function in individuals with SCI. Five individuals with American Spinal Injury Association Impairment Scale A/B, chronic SCI and detrusor sphincter dyssynergia enrolled in this prospective, interventional study. After a two-week assessment to determine effective stimulation characteristics, each patient received sixteen weekly TMSCS treatments and then received “sham” weekly stimulation for six weeks while bladder function was monitored. Bladder function improved in all five subjects, but only during and after repeated weekly sessions of 1 Hz TMSCS. All subjects achieved volitional urination. The volume of urine produced voluntarily increased from 0 cc/day to 1120 cc/day (p = 0.03); self-catheterization frequency decreased from 6.6/day to 2.4/day (p = 0.04); the capacity of the bladder increased from 244 ml to 404 ml (p = 0.02); and the average quality of life ranking increased significantly (p = 0.007). Volitional bladder function was re-enabled in five individuals with SCI following intermittent, non-invasive TMSCS. We conclude that neuromodulation of spinal micturition circuitry by TMSCS may be used to ameliorate bladder function.

Lumbar spinal stenosis (LSS) is a condition associated with the degeneration of spinal disks in the lower back. A significant majority of the elderly population experiences LSS, and the number is expected to grow. The primary objective of medical treatment for LSS patients has focused on improving functional outcomes (e.g., walking ability) and thus, an accurate, objective, and inexpensive method to evaluate patients' functional levels is in great need. This paper aims to quantify the functional level of LSS patients by analyzing their clinical information and their walking ability from a 10 m self-paced walking test using a pair of sensorized shoes. Machine learning algorithms were used to estimate the Oswestry Disability Index, a clinically well-established functional outcome, from a total of 29 LSS patients. The estimated ODI scores showed a significant correlation to the reported ODI scores with a Pearson correlation coefficient (r) of 0.81 and p<3.5×10(-11). It was further shown that the data extracted from the sensorized shoes contribute most to the reported estimation results, and that the contribution of the clinical information was minimal. This study enables new research and clinical opportunities for monitoring the functional level of LSS patients in hospital and ambulatory settings.