Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation.

OBJECTIVE: High-frequency spinal cord stimulation (HF-SCS) is a potential method to provide natural and effective inspiratory muscle pacing in patients with ventilator-dependent spinal cord injuries. Experimental data have demonstrated that HF-SCS elicits physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways. However, the activation thresholds, extent of activation, and optimal electrode configurations (i.e., lead separation, contact spacing, and contact length) to activate these neural elements remain unknown. Therefore, the goal of this study was to use a computational modeling approach to investigate the direct effects of HF-SCS on the spinal cord and to optimize electrode design and stimulation parameters. MATERIALS AND METHODS: We developed a computer model of HF-SCS that consisted of two main components: 1) finite element models of the electric field generated during HF-SCS, and 2) multicompartment cable models of axons and motoneurons within the spinal cord. We systematically evaluated the neural recruitment during HF-SCS for several unique electrode designs and stimulation configurations to optimize activation of these neural elements. We then evaluated our predictions by testing two of these lead designs with in vivo canine experiments. RESULTS: Our model results suggested that within physiological stimulation amplitudes, HF-SCS activates both axons in the ventrolateral funiculi (VLF) and inspiratory intercostal motoneurons. We used our model to predict a lead design to maximize HF-SCS activation of these neural targets. We evaluated this lead design via in vivo experiments, and our computational model predictions demonstrated excellent agreement with our experimental testing. CONCLUSIONS: Our computational modeling and experimental results support the potential advantages of a lead design with longer contacts and larger edge-to-edge contact spacing to maximize inspiratory muscle activation during HF-SCS at the T2 spinal level. While these results need to be further validated in future studies, we believe that the results of this study will help improve the efficacy of HF-SCS technologies for inspiratory muscle pacing.

Effects of Lower Thoracic Spinal Cord Stimulation on Bowel Management in Individuals With Spinal Cord Injury.

OBJECTIVE: To systematically determine whether use of the spinal cord stimulation (SCS) system to restore cough may improve bowel management (BM) in individuals with spinal cord injury (SCI). DESIGN: Experimental studies (clinical trial). SETTING: Inpatient hospital setting for electrode insertion; outpatient setting for measurement of respiratory pressures; home setting for application of SCS. PARTICIPANTS: Participants (N=5) with cervical SCI. INTERVENTION: A fully implantable SCS cough system was surgically placed in each subject. SCS was applied at home, 2-3 times/d, on a chronic basis, every time bowel regimen was performed and as needed for secretion management. Stimulus parameters were set at values resulting in near maximum airway pressure generation, which was used as an index of expiratory muscle strength. Participants also used SCS during their bowel routine. MAIN OUTCOME MEASURES: Airway pressure generation achieved with SCS. Weekly completion of Bowel Routine Log including BM time, mechanical measures, and medications used. RESULTS: Mean pressure during spontaneous efforts was 30±8 cmH2O. After a period of reconditioning, SCS resulted in pressure of 146±21 cmH2O. The time required for BM routines was reduced from 118±34 minutes to 18±2 minutes (P<.05) and was directly related to the magnitude of pressure development during SCS. Mechanical methods for BM were completely eliminated in 4 patients. No patients experienced fecal incontinence as result of SCS. Each participant also reported marked overall improvement associated with BM. CONCLUSIONS: Our results of this pilot study suggest that SCS to restore cough may be a useful method to improve BM and life quality for both patients with SCI and their caregivers. Our results indicate that the improvement in BM is secondary to restoration of intra-abdominal pressure development.

Long-term follow-up of spinal cord stimulation to restore cough in subjects with spinal cord injury.

OBJECTIVE: To determine the long-term effects of the cough stimulation system. DESIGN: Nonrandomized clinical trial of subjects using the study device well beyond the period of close follow-up. SETTING: Use of the study device in the home setting. PARTICIPANTS: Subjects (N = 10) implanted with the device for a minimum of 2 years (mean 4.6 ± 0.6 years). INTERVENTIONS: Application of daily stimulation. OUTCOME MEASURES: Airway pressure generation and other clinical assessments including ease in raising secretions, life quality, caregiver support, and incidence of respiratory tract infections were measured at 1 year and mean 4.6 years after implantation. RESULTS: Each subject continued to use the device on a regular basis. During SCS, mean maximum airway pressures were 103.1 ± 20.4 and 107.7 ± 23.0 cm H2O at the 1-year and mean 4.6-year follow-up points, respectively (P < 0.05 compared with pre-implant and not significantly different (NS) compared with 1-year follow-up). Benchmarks related to ease in raising secretions and improvements in life quality related to respiratory care were maintained at the mean 4.6 year follow-up. The need for trained caregivers to provide other means of secretion management remained significantly below the pre-implant values (P < 0.05). The incidence of acute respiratory tract infections remained low at 0.2 ± 0.1 events/year, which is significantly below the pre-implant value of 1.4 ± 0.3 events/year (P < 0.05). CONCLUSION: Subjects continued to use the system on a long-term basis beyond the period of close follow-up and to continued derive significant clinical benefits.

Impact of the cough stimulation system on the care burden and life quality of caregivers of tetraplegics.

OBJECTIVES: To determine caregiver burden and quality of life of primary family caregivers of participants with cervical SCI before and after use of the cough stimulation system (CSS). DESIGN: Prospective assessment at four timepoints via questionnaire responses. SETTING: Out-patient hospital, United States. PARTICIPANTS: 15 primary family caregivers of participants with cervical SCI completed questionnaires including a respiratory care burden index (n = 15) and a commonly employed caregiver burden inventory (n = 9), before and at the 6-month, 1-year and 2-year timepoints following use of the CSS. RESULTS: SCI participants had significant clinical improvements in terms of restoration of an effective cough and ability to manage airway secretions with use of the CSS. Restoration of expiratory muscle function with use of the CSS also resulted in less caregivers (CG) stress, greater control of their participants' breathing problems, and improvement in quality of life. Results of the caregiver burden inventory demonstrated marked reductions in caregiver burden in development items, physical health and social relationship. Overall caregiver burden fell from 43.4 ± 13.8 pre-implant to 32.4 ± 7.9 (P = 0.06), 31.7 ± 10.5 (P = 0.05), and 26.5 ± 9.3 (P = 0.01) at the 6-month, 1-year and 2-year timepoints. CONCLUSION: Use of the CSS by cervical SCI participants results in restoration of an effective cough with significant clinical benefits. While caregiver burden is very high in primary family caregivers, they derive marked improvement in caregiver burden and quality of life with implementation of this device.Trial registration: ClinicalTrials.gov identifier: NCT00116337.Trial registration: ClinicalTrials.gov identifier: NCT01659541.

Phrenic-to-intercostal reflex activity in response to high frequency spinal cord stimulation (HF-SCS).

OBJECTIVE: HF-SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic-to-intercostal reflex during HF-SCS. METHODS: In 5 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the left and right external intercostal muscles (EI) in the 3rd interspace before and after sequential left and right phrenicotomy. RESULTS: Mean control peak firing frequency of the right EI and left EI was 11.4 ± 0.3 Hz and 10.6 ± 0.3 Hz respectively. Following unilateral right phrenic nerve section, mean SMU peak firing frequency of right EI (ipsilateral to the section) was significantly greater when compared to control (15.9 ± 0.5 Hz vs 11.4 ± 0.3 Hz; p = 0.01). Mean SMU peak firing frequency of the contralateral left EI remained unchanged (10.2 ± 0.3 Hz vs 10.6 ± 0.3 Hz, p = 0.40). Subsequent, section of the left phrenic nerve resulted in significantly higher mean SMU peak firing frequency of the left EI (16.2 ± 0.5 Hz vs 10.2 ± 0.3 Hz) when compared to before section p = 0.01). Contralateral, right EI peak firing frequency was not different if compared to before left phrenic nerve section (16.9 ± 0.4 Hz vs. 15.9 ± 0.5 Hz; p = 0.14). CONCLUSION: This study demonstrates that during HF-SCS: 1) unilateral diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral EI muscles, 2) the neural circuitry mediating the phrenic-to-intercostal reflex is preserved at a spinal level and does not require supraspinal input and 3) unilateral compensatory increases were observed in EI muscle activation following ipsilateral diaphragm paralysis.

Comparison of disc and wire electrodes to restore cough via lower thoracic spinal cord stimulation.

OBJECTIVE: To compare the safety and effectiveness of wire (WE) vs. disc (DE) electrodes to restore cough in subjects with spinal cord injury (SCI). DESIGN: Clinical trials assessing the effectiveness and clinical outcomes associated with two electrode systems to activate the expiratory muscles. SETTING: Inpatient hospital setting for DE or WE electrode insertion; outpatient evaluation of cough efficacy and instructions for home use. PARTICIPANTS: Twenty-nine subjects with SCI; 17 participants with DE and 12 with WE implants. INTERVENTION: Surgical implantation of WE or DE to restore cough. Daily application of spinal cord stimulation (SCS) at home. MAIN OUTCOME MEASURE(S): Airway pressure (P) and peak airflow (F) generation achieved with SCS; clinical parameters including ease in raising secretions, incidence of acute respiratory tract infections (RTI) and side effects. RESULTS: P and F achieved with DE and WE were not significantly different. For example, at total lung capacity (TLC) with participant effort, P was 128 ± 12 cmH2O and 118 ± 14 cmH2O, with DE and WE, respectively. The degree of difficulty in raising secretions improved markedly in both groups. The incidence of RTI per year fell from 1.3 ± 0.3 and 1.3 ± 0.5-0.3 ± 0.1 and 0.1 ± 0.1 for DE and WE groups, respectively (P < 0.01 for both when compared to pre-implant values and NS between DE and WE groups). The only significant side effect i.e. short-term autonomic dysreflexia was also similar between groups. CONCLUSIONS: The results of this investigation indicate that both DE and WE result in comparable degrees of expiratory muscle activation, clinical benefits and side effects. Importantly, SCS to restore cough can be achieved with use of WE which can be placed using minimally invasive techniques and associated reduction in cost, surgical time and overall risk.Trial registration: ClinicalTrials.gov identifier: NCT00116337., NCT01659541, FDA IDE: G980267.

Effects of restoration of cough via spinal cord stimulation on subject quality of life.

Objectives: To determine participant quality of life before and after use of the cough stimulation system (Cough System). Design: Prospective assessment of life quality at 4 timepoints via questionnaire responses. Setting: Out-patient hospital, United States. Participants: 28 subjects with spinal cord injury (SCI) completed life quality assessment questionnaires before and at the 28- 40- and 52-week timepoints following use of the Cough System. Results: Each subject demonstrated significant clinical improvements in terms of restoration of an effective cough and ability to manage airway secretions with use of the Cough System. Positive airway pressures and peak expiratory airflows approached values associated with a normal cough. Related to cough/secretion management, use of this system also resulted less interference with family life and daily activities, less financial difficulties, less requirement for caregiver assistance, less stress, less embarrassment and greater control of their breathing problems (p < 0.01), for each comparison). There also significant improvements in that their overall health and quality of life (p < 0.01, for each comparison). Subjects also reported greater ease in breathing, restored ability to sneeze and enhanced mobility. The incidence of acute respiratory tract infections fell from 1.3 ± 0.3 to 0.2 ± 0.1 events/subject year (p < 0.01). Ten subjects developed mild hemodynamic effects consistent with autonomic dysreflexia that abated completely with continued use of the Cough System. Some subjects experienced mild leg jerks during SCS, which were well tolerated and abated completely with reduction in stimulus amplitude, No subjects reported bowel or bladder leakage. Conclusion: Use of the Cough System by SCI subjects is a safe and efficacious method which significantly improves life quality and has the potential to reduce the mortality and morbidity associated with SCI.

Distribution of electrical activation to the external intercostal muscles during high frequency spinal cord stimulation in dogs.

In contrast to previous methods of electrical stimulation of the inspiratory muscles, high frequency spinal cord stimulation (HF-SCS) results in more physiological activation of these muscles. The spatial distribution of activation to the external intercostal muscles by this method is unknown. In anaesthetized dogs, multiunit and single motor unit (SMU) EMG activity was monitored in the dorsal portion of the 3rd, 5th and 7th interspaces and ventral portion of the 3rd interspace during spontaneous breathing and HF-SCS following C2 spinal section. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes matched spontaneous breathing (Protocol 1). During HF-SCS, mean peak SMU firing frequency was highest in the 3rd interspace (dorsal) (18.8 ± 0.3 Hz) and significantly lower in the 3rd interspace (ventral) (12.2 ± 0.2 Hz) and 5th interspace (dorsal) (15.3 ± 0.3 Hz) (P <0.05 for each comparison). Similar rostrocaudal and dorsoventral gradients of activity were observed during spontaneous breathing prior to C2 section. No significant activity was observed in the 7th interspace during either spontaneous breathing or HF-SCS. Since peak discharge frequencies of the SMUs were higher and rib cage movement greater during HF-SCS compared to spontaneous breathing, stimulus amplitude during HF-SCS was adjusted such that rib cage movement matched (Protocol 2). Under these conditions, mean peak SMU frequencies and rostrocaudal and dorsoventral gradients of activity during HF-SCS were not significantly different compared to spontaneous breathing. These results indicate that (a) the topographic pattern of electrical activation of the external intercostal muscles during HF-SCS is similar to that occurring during spontaneous breathing and (b) differential descending synaptic input from supraspinal centres is not a required component of the differential spatial distribution of external intercostal muscle activation. HF-SCS may provide a more physiological method of inspiratory muscle pacing.

Comparison of wire and disc leads to activate the expiratory muscles in dogs.

OBJECTIVE: Respiratory complications account for a major cause of morbidity and mortality in subjects with spinal cord injury (SCI) due to paralysis of the expiratory muscles and the consequent inability to generate effective cough. We demonstrated previously that effective cough can be restored in SCI via spinal cord stimulation (SCS) with disc leads positioned on the lower thoracic and upper lumbar spinal cord via laminotomy incisions. In this study, the effectiveness of wire leads, which can be placed using minimally invasive techniques, to activate the expiratory muscles was evaluated. DESIGN: Animal study. SETTING: Research laboratory. ANIMALS: Dogs (n = 8). INTERVENTIONS: In separate trials, disc and wire leads were inserted onto the dorsal epidural space at the T9, T11, and L1 spinal cord levels. Effects of electrical stimulation with disc, single wire, and two wire leads placed in parallel were compared. OUTCOME MEASURES: Airway pressure generation following stimulation with disc and various configurations of wire leads were compared. RESULTS: Several different configurations of wire leads resulted in airway pressures that were similar to those generated with monopolar stimulation with disc leads (MSDLs). For example, combined monopolar stimulation with parallel wire leads at the T9 + T11 and T9 + L1 levels resulted in airway pressures that were 103.5 ± 6.4 and 101.9 ± 7.0%, respectively, of those achieved with MSDL. Bipolar stimulation with parallel wire leads at T9-T11 and T9-L1 resulted in airway pressures that were 94.2 ± 3.4 and 96.8 ± 5.0%, respectively, of the pressures achieved with MSDL. Other wire configurations were also evaluated, but were generally less effective. CONCLUSION: These results suggest that specific configurations of wire leads, which can be placed via minimally invasive techniques, result in comparable activation of the expiratory muscles compared to disc leads and may be a useful technique to restore cough in persons with SCI.

Comparison of wire and disc electrodes to electrically activate the inspiratory muscles in dogs.

OBJECTIVE: To compare the effectiveness of wire versus disc electrodes to activate the inspiratory muscles via high frequency spinal cord stimulation. DESIGN: Animal study. SETTING: Research laboratory. ANIMALS: Dogs (n = 5) INTERVENTIONS: In separate trials, spinal cord stimulation (SCS) was applied via disc (DE) and two parallel wire electrodes (WE) on the ventral epidural space at the T2-T3 spinal region. MAIN OUTCOME MEASURE(S): Airway pressure (P) and inspired volume (V) generation following stimulation with DE and WE were compared. Given our previous success with (DE), outcome variables with this electrode were used as our gold standard to which all comparisons were made. RESULTS: Two configurations of WE using monopolar stimulation (MS) resulted in P and V that were similar to those generated with MS with DE. For example, MS with parallel WE connected together to function as a common cathode (Y-connection) and a 2-channel system (separate cathodes with a remote ground), resulted in P that were 91 ±â€¯6 and 92 ±â€¯4%, respectively, of those achieved with DE (NS for both). Bipolar stimulation with parallel WE using a Y-connection and with a 2-channel system, resulted in P that were 96 ±â€¯4 and 94 ±â€¯4%, of the P achieved with DE (NS for both). CONCLUSION(S): These results suggest that specific configurations of WE, which can be placed via minimally invasive techniques, provide comparable activation of the inspiratory muscles compared to DE and may be a useful technique to restore ventilatory support in persons with spinal cord injury.

Activation of the expiratory muscles via lower thoracic high frequency spinal cord stimulation in awake animals.

Lower thoracic spinal cord stimulation is an effective method of restoring an effective cough in participants with complete spinal cord injury. The high voltage requirements however significantly limits this application in subjects with intact lower chest wall sensation. In anesthetized animals, we have shown that the expiratory muscles can also be effectively activated with low stimulus currents (1 mA) but with high stimulus frequencies (HF-SCS -500 Hz). In 3 intact, awake pigs the responses to HF-SCS, were evaluated. HF-SCS was associated with marked expansion of the abdominal wall and external oblique EMG activity without any associated changes in heart rate or vocalization. During a terminal procedure under general anesthesia, responses to HF-SCS were re-assessed. Abdominal movement and EMG were similar to that observed in the awake state. HF-SCS (1.5 mA) resulted in an airway pressure of 65 ± 2cmH2O. Our results indicate that lower thoracic HF-SCS may be a useful method to restore an effective cough in patients with intact chest wall sensation.

Restoration of cough via spinal cord stimulation improves pulmonary function in tetraplegics.

Background: Spinal cord injury (SCI) results in significant loss in pulmonary function secondary to respiratory muscle paralysis. Retention of secretions and atelectasis and, recurrent respiratory tract infections may also impact pulmonary function. Objective: To determine whether usage of lower thoracic spinal cord stimulation (SCS) to restore cough may improve spontaneous pulmonary function in individuals with chronic SCI. Design/Methods: 10 tetraplegics utilized SCS system on a regular daily basis. Spontaneous inspiratory capacity (IC), maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) were measured at baseline prior to usage of the device and repeated every 4-5 weeks over a 20-week period. Maximum airway pressure generation (P) during SCS (40 V, 50 Hz, 0.2 ms) at total lung capacity (TLC) with subject maximal expiratory effort, at the same timepoints were determined, as well. Results: Following daily use of SCS, mean IC improved from 1636 ± 229 to 1932 ± 239 ml (127 ± 8% of baseline values) after 20 weeks (P < 0.05). Mean MIP increased from 40 ± 7, to 50 ± 8 cmH2O (127 ± 6% of baseline values) after 20 weeks, respectively (P < 0.05). MEP also improved from 27 ± 3.7 to 33 ± 5 (127 ± 14% of baseline values) (NS). During SCS, P increased from baseline in all participants from mean 87 ± 8 cmH2O to 117 ± 14 cmH2O at weeks 20, during TLC with subject maximal expiratory effort, respectively (P < 0.05). Each subject stated that they experienced much greater ease in raising secretions with use of SCS. Conclusion: Our findings indicate that use of SCS not only improves expiratory muscle function to restore cough but also results in improvement inspiratory function, as well.

Initial assessment and management of respiratory infections in persons with spinal cord injuries and disorders in the COVID-19 era.

As the COVID-19 pandemic unfolds, emergency department (ED) personnel will face a higher caseload, including those with special medical needs such as persons living with spinal cord injuries and disorders (SCI/D). Individuals with SCI/D who develop COVID-19 are at higher risk for rapid decompensation and development of acute respiratory failure during respiratory infections due to the combination of chronic respiratory muscle paralysis and autonomic dysregulation causing neurogenic restrictive/obstructive lung disease and chronic immune dysfunction. Often, acute respiratory infections will lead to significant mucus production in individuals with SCI/D, and aggressive secretion management is an important component of successful medical treatment. Secretion management techniques include nebulized bronchodilators, chest percussion/drainage techniques, manually assisted coughing techniques, nasotracheal suctioning, and mechanical insufflation-exsufflation. ED professionals, including respiratory therapists, should be familiar with the significant comorbidities associated with SCI/D and the customized secretion management procedures and techniques required for optimal medical management and prevention of respiratory failure. Importantly, protocols should also be implemented to minimize potential COVID-19 spread during aerosol-generating procedures.

High-frequency spinal cord stimulation of inspiratory muscles in dogs: a new method of inspiratory muscle pacing.

Despite clinically available methods of diaphragm pacing, most patients with ventilator-dependent tetraplegia are still dependent on mechanical ventilation. Given the significant disadvantages of these devices, additional pacing options are needed. The objective of this study was to evaluate a novel and potentially more physiological method of inspiratory muscle activation, which involves the application of high-frequency (>200 Hz) stimulation to the ventral surface of the spinal cord in the high thoracic region. Studies were performed in 13 anesthetized dogs. High-frequency spinal cord stimulation (HF-SCS) results in the activation of both the diaphragm and inspiratory intercostal muscles, in concert, at physiological firing frequencies and the generation of large inspired volumes. Mean maximum firing frequencies of motor units in the parasternal (2nd interspace), the external intercostal (3rd interspace), and the diaphragm muscles were 10.6 +/- 0.4, 11.7 +/- 0.4, and 10.4 +/- 0.3 Hz, respectively. These values were not significantly different from those occurring during spontaneous breathing at comparable inspired volumes. Maximum inspired volume was 0.93 +/- 0.01 liter, which approximates the inspiratory capacity of these animals. Moreover, ventilation can be maintained on a chronic basis by this method (6 h) without evidence of system fatigue. Our results suggest that HF-SCS results in activation of spinal cord tracts that synapse with the inspiratory motoneuron pools, allowing processing of the stimulus and consequent physiological activation of the inspiratory muscles. HF-SCS has the potential to provide an effective method of inspiratory muscle pacing.

Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-sponsored clinical trial. Part I: methodology and effectiveness of expiratory muscle activation.

OBJECTIVE: Evaluation of the capacity of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles and generate large airway pressures and high peak airflows characteristic of cough, in subjects with tetraplegia. DESIGN: Clinical trial. SETTING: Inpatient hospital setting for electrode insertion; outpatient setting for measurement of respiratory pressures; home setting for application of SCS. PARTICIPANTS: Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury and weak cough. INTERVENTIONS: A fully implantable electrical stimulation system was surgically placed in each subject. Partial hemilaminectomies were made to place single-disk electrodes in the epidural space at the T9, T11, and L1 spinal levels. A radiofrequency receiver was placed in a subcutaneous pocket over the anterior portion of the chest wall. Electrode wires were tunneled subcutaneously and connected to the receiver. Stimulation was applied by activating a small portable external stimulus controller box powered by a rechargeable battery to each electrode lead alone and in combination. MAIN OUTCOME MEASURES: Peak airflow and airway pressure generation achieved with SCS. RESULTS: Supramaximal SCS resulted in high peak airflow rates and large airway pressures during stimulation at each electrode lead. Maximum peak airflow rates and airway pressures were achieved with combined stimulation of any 2 leads. At total lung capacity, mean maximum peak airflow rates and airway pressure generation were 8.6+/-1.8 (mean +/- SE) L/s and 137+/-30 cmH2O (mean +/- SE), respectively. CONCLUSIONS: Lower thoracic SCS results in near maximum activation of the expiratory muscles and the generation of high peak airflow rates and positive airway pressures in the range of those observed with maximum cough efforts in healthy persons.

Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-Sponsored clinical trial. Part II: clinical outcomes.

OBJECTIVE: To evaluate the clinical effects of spinal cord stimulation (SCS) to restore cough in subjects with cervical spinal cord injury. DESIGN: Clinical trial assessing the clinical outcomes and side effects associated with the cough system. SETTING: Outpatient hospital or residence. PARTICIPANTS: Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury. INTERVENTIONS: SCS was performed at home by either the subjects themselves or caregivers on a chronic basis and as needed for secretion management. MAIN OUTCOME MEASURES: Ease in raising secretions, requirement for trained caregiver support related to secretion management, and incidence of acute respiratory tract infections. RESULTS: The degree of difficulty in raising secretions improved markedly, and the need for alternative methods of secretion removal was virtually eliminated. Subject life quality related to respiratory care improved, with subjects reporting greater control of breathing problems and enhanced mobility. The incidence of acute respiratory tract infections fell from 2.0+/-0.5 to 0.7+/-0.4 events/subject year (P<.01), and mean level of trained caregiver support related to secretion management measured over a 2-week period decreased from 16.9+/-7.9 to 2.1+/-1.6 and 0.4+/-0.3 times/wk (P<.01) at 28 and 40 weeks after implantation of the device, respectively. Three subjects developed mild hemodynamic effects that abated completely with continued SCS. Subjects experienced mild leg jerks during SCS, which were well tolerated. There were no instances of bowel or bladder leakage. CONCLUSIONS: Restoration of cough via SCS is safe and efficacious. This method improves life quality and has the potential to reduce the morbidity and mortality associated with recurrent respiratory tract infections in this patient population.

High-frequency spinal cord stimulation in a subacute animal model of spinal cord injury.

High-frequency spinal cord stimulation (HF-SCS) applied at the T2 spinal level results in physiologic activation of the inspiratory muscles in C2 spinal-sectioned dogs. Although the bulbo-spinal fibers were cut, they likely survived the duration of acute experiments, and inspiratory muscle activation may have involved stimulation of these fibers. In two anesthetized, C2 paralyzed, intubated, and mechanically ventilated dogs, HF-SCS (300 Hz) was applied at the T2 level. The effectiveness of HF-SCS in generating inspired volume (V) and negative airway pressures (P) was evaluated over a period of 5 days during which time the bulbo-spinal fibers would have degenerated. Because the effectiveness of HF-SCS may be adversely affected by deterioration of these fibers and/or the condition of the animal, low-frequency (50 Hz) SCS (LF-SCS) was also performed and served as a control. All vital signs, oxygen saturation, and end-tidal Pco2 remained stable over the 5-day period. V and P also remained stable over the study period. For example, mean V and P were 771 ± 25 ml and 64 ± 1 cmH2O with HF-SCS (3 mA) during the initial and 674 ± 59 ml and 63 ± 5 cmH2O on the final day. Comparable values during LF-SCS (8 mA) were 467 ± 12 ml and 48 ± 1 cmH2O during the initial and 397 ± 20 ml and 42 ± 2 cmH2O on the final day. Because V and P in response to HF-SCS remained stable over a 5-day period following which the bulbo-spinal fibers would have degenerated, the mechanism of HF-SCS does not depend upon the viability of these tracts. HF-SCS therefore may be a useful method to restore ventilation in chronic ventilator dependent tetraplegics. NEW & NOTEWORTHY This study indicates that the respiratory responses to high-frequency spinal cord stimulation applied at the T2 level results in activation of the inspiratory motoneuron pools via interneuronal circuits and/or the inspiratory motoneurons directly and does not depend upon activation of long descending inspiratory bulbo-spinal fibers. This method therefore, may provide an alternative method to restore ventilation in ventilator dependent spinal cord injured patients.

Inspiratory muscle activation via ventral lower thoracic high-frequency spinal cord stimulation.

In animals, high-frequency spinal cord stimulation (HF-SCS) applied on the ventral epidural surface at the T2 level results in negative airway pressure generation consistent with inspiratory muscle activation. In the present study, in anesthetized dogs, we found that ventral HF-SCS (500 Hz) applied at all thoracic levels resulted in negative airway pressure generation. In the region of the lower thoracic spinal cord, negative airway pressure generation was most pronounced at the T9 level. At this level, airway pressure generation was monitored: 1) during ventral HF-SCS over a wide range of stimulus amplitudes (0.5-15 mA) and frequencies (50-1,000 Hz) and 2) following spinal sections at C8 (to assess potential diaphragm activation) and subsequently at T6 (to assess potential intercostal muscle activation). The application of low stimulus currents between 1 and 2 mA and high stimulus frequencies (>300 Hz) resulted in the development of large negative airway pressure generation. Stimulation with 1 mA, 500 Hz resulted in a highest negative airway pressure generation of 47 ± 2 cmH2O. Increasing stimulus current was associated with progressive reductions in the magnitude of negative airway pressure generation. HF-SCS (500 Hz) with 15 mA resulted in a negative airway pressure generation of 7 ± 3 cmH2O. C8 section markedly reduced negative airway pressure generation, and subsequent T6 section resulted in positive airway pressure generation after HF-SCS. Our results indicate the existence of pathways with connections to both the phrenic and inspiratory intercostal motoneuron pools in the ventral part of the lower thoracic spinal cord. We speculate that the circuits mediating the previously described excitatory intercostal-to-phrenic reflex mediate the observed responses. NEW & NOTEWORTHY This study suggests that, in contrast to dorsal high-frequency spinal cord stimulation at the T9 spinal level, which results in positive pressure generation, ventral high-frequency spinal cord stimulation at the same spinal level results in large negative airway pressure generation with low stimulus currents. This method, therefore, may provide an alternative method to restore ventilation in ventilator-dependent spinal cord-injured patients.

Complete Restoration of Respiratory Muscle Function in Three Subjects With Spinal Cord Injury: Pilot Interventional Clinical Trial.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of complete restoration of respiratory muscle function in subjects with spinal cord injury. METHODS: This was an interventional study investigating three subjects maintained on a diaphragm pacing system who were implanted with the spinal cord stimulation system to restore cough. Peak expiratory airflow and airway pressure generation were the primary physiologic outcome measures; an assessment of the degree of difficulty in raising secretions was the primary clinical outcome measure. RESULTS: Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH2O, respectively. When spinal cord stimulation was applied after pacing volume associated with the subject's maximum inspiratory effort and synchronized with the subject's maximum expiratory effort, peak expiratory airflow and airway pressure generation were 9.0 ± 1.9 L/s and 90 ± 6 cmH2O, respectively (P < 0.05). Moreover, each subject experienced much greater ease in raising secretions and marked improvement in the ease in raising secretions compared with other methods. CONCLUSIONS: Complete restoration of respiratory muscle function can be safely and effectively achieved in the same individuals with spinal cord injury. Spinal cord stimulation results in peak expiratory airflow and airway pressure generation characteristic of a normal cough, whereas diaphragm pacing was successful in maintaining patients off mechanical ventilation.