Krzysztof E. Kowalski

Inspiratory Muscle Pacing in Spinal Cord Injury: Case Report and Clinical Commentary

Abstract Background/Objective: A significant fraction of patients with cervical spinal cord injury suffer from respiratory muscle paralysis and dependence on chronic mechanical ventilation. In selected patients, diaphragm pacing (DP) through electrical stimulation of the phrenic nerves provides an alternative to mechanical ventilation with significant advantages in life quality. Methods: A case report of an individual who successfully underwent DP using intramuscular diaphragm electrodes. A brief review of the state of the art of DP including the clinical benefits of DP, patient selection and evaluation, description of equipment, methods of transition from mechanical ventilation to DP, potential complications and side effects, long-term outcome, and potential future developments in this field is included. Results: Several available DP systems are available, including conventional ones in which electrodes are positioned directly on the phrenic nerves through thoracotomy and less invasive systems in which electrodes are placed within the diaphragm through laparoscopy. For patients with only unilateral phrenic nerve function, a combined intercostal and unilateral diaphragm pacing system is under development. Conclusions: In patients with ventilator-dependent tetraplegia, there are alternative methods of ventilatory support, which offer substantial benefits compared to mechanical ventilation.

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.

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

Non‐technical summary  Normal breathing is controlled by specialized neurons in the central nervous system including the brainstem and spinal cord. Signals generated in the brainstem and transmitted to the major inspiratory muscles, including the diaphragm and intercostal muscles, are necessary to sustain life. However, we show that the specific pattern of intercostal muscle activation during breathing does not require input from the brainstem. In other words, the neural circuitry controlling this pattern of activation exists within the spinal cord. This knowledge furthers our understanding of the mechanisms that control breathing and has implications for patients with certain disease states such as cervical spinal cord injury.

Diaphragm activation via high frequency spinal cord stimulation in a rodent model of spinal cord injury.

As demonstrated in a canine model, high frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of electrical activation of the inspiratory muscles compared to current techniques. The dog model, however, has significant limitations due to cost and societal concerns. Since the rodent respiratory system is also a relevant model for the study of neuronal circuitry function, the aims of the present study were to a) assess the effects of HF-SCS and b) determine the methodology of application of this technique in rats. In 9 Sprague Dawley rats, diaphragm multiunit and single motor unit EMG activity were assessed during spontaneous breathing and HF-SCS applied on the ventral epidural surface of the spinal cord at the T2 level following C1 spinal section. As in dogs, HF-SCS results in the activation of the diaphragm at physiological firing frequencies and the generation of large inspired volumes. Mean maximum firing frequencies of the diaphragm during spontaneous breathing and HF-SCS were 23.3 ± 1.4 Hz (range: 9.8-51.6 Hz) and 26.6 ± 1.3 Hz; range: 12.0-72.9 Hz, respectively, at comparable inspired volumes. Moreover, HF-SCS was successful in pacing these animals over a 60-min period without evidence of system fatigue. Our results suggest that, similar to the dog model, HF-SCS in the rat results in the activation of spinal cord tracts which synapse with the phrenic motoneuron pool, allowing the processing of the stimulus and consequent physiologic activation of the inspiratory muscles. The rat may be a useful model for further studies evaluating phrenic motoneuron physiology.

Activation of inspiratory muscles via spinal cord stimulation.

Diaphragm pacing is a clinically useful modality providing artificial ventilatory support in patients with ventilator dependent spinal cord injury. Since this technique is successful in providing full-time ventilatory support in only ~50% of patients, better methods are needed. In this paper, we review a novel method of inspiratory muscle activation involving the application of electrical stimulation applied to the ventral surface of the upper thoracic spinal cord at high stimulus frequencies (300 Hz). In an animal model, high frequency spinal cord stimulation (HF-SCS) results in synchronous activation of both the diaphragm and inspiratory intercostal muscles. Since this method results in an asynchronous pattern of EMG activity and mean peak firing frequencies similar to those observed during spontaneous breathing, HF-SCS is a more physiologic form of inspiratory muscle activation. Further, ventilation can be maintained on a long-term basis with repetitive stimulation at low stimulus amplitudes (<1 mA). These preliminary results suggest that HF-SCS holds promise as a more successful method of inspiratory muscle pacing.

Intercostal Muscle Pacing with High Frequency Spinal Cord Stimulation in Dogs

High frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of inspiratory muscle activation which involves stimulation of spinal cord pathways. In the present study, we determined if activation of the inspiratory intercostal muscles alone by this technique could be utilized to maintain artificial ventilation. In 7 anesthetized dogs, following C2 spinal cord section and bilateral phrenicotomy, trains of electrical stimulation (12 times/min) were applied at the T2 level. Eucapnea was maintained during an initial 5.5h period of continuous stimulation. During a subsequent 0.5h period, stimulus parameters were increased to induce hyperventilation resulting in a sustained fall in end-tidal P(CO(2)) to 29.3 + or - 0.4 mmHg. Single motor unit peak firing frequencies of the intercostal muscles during HF-SCS were similar to those occurring during spontaneous breathing. This technique holds promise as a method to restore ventilation in ventilator-dependent tetraplegics who do not have adequate phrenic nerve function for diaphragm pacing.

Spinal Pathways Mediating Phrenic Activation during High Frequency Spinal Cord Stimulation

High frequency spinal cord stimulation (HF-SCS) is a method of inspiratory muscle activation resulting in phrenic motoneuron activation via stimulation of spinal cord pathways. The specific pathways mediating this response, however, are unknown. The aim of this study was to assess the potential role of upper cervical (C1-C4) pre-phrenic interneurons (UCI) and localize the pathways in the thoracic spinal cord mediating activation of phrenic motoneurons during HF-SCS. In 7 anesthetized, spinalized (C1 level) dogs, HF-SCS was applied at the T2 level. Diaphragm EMG, inspired volume and airway pressure generation were monitored before and following sequential spinal cord sections at the C4 and C8 levels. Section at the C4 level and dorsal columns at C8 resulted in no significant changes. However, lateral funiculi section (C8 level) resulted in significant reductions in each parameter. We conclude that during upper thoracic HF-SCS, the phrenic motoneuron pools are activated via spinal pathways located in the lateral funiculus but UCI are not involved.

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

Abstract 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 cmH2O 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.