Background: High Frequency Spinal Cord Stimulation (HF-SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. Objective: To examine the effects of spinal segmental afferents on1) inspiratory intercostal muscle activation during loaded breathing and 2) post-inspiratory activity following HF-SCS. Methods: In 6 anesthetized and C2 spinalized dogs, a laminectomy was performed over the thoracic spine from the T1 to T5 levels. A stimulating disc electrode was positioned on the ventral surface of the spinal cord at the T2 level. Recording electrodes were placed in the parasternal (PA) and external (EI) intercostal muscles (2 nd and 3 rd interspaces respectively) to record multiunit EMG activity. During HF-SCS inspiratory intercostal muscle activity was assessed before and after bilateral dorsal rhizotomy (from T1-T5) following single breath airway occlusion. Results: During HF-SCS, tracheal occlusion resulted in augmentation of peak multi-unit integrated EI, but little change in PA EMG activity. During the occluded breath, EI activity increased to 174±6% of that observed during control breaths (p<0.01) whereas PA activity was unchanged (105±2%; NS). Following dorsal rhizotomy, facilitation of EI activity was significantly reduced (121±4%, p<0.05), and PA activity was unchanged (99±2%, NS). Under control conditions, there was significant post-inspiratory activity in the EI but only minimal activity in the PA. Following dorsal rhizotomy, post-inspiratory activity was absent. Summary: Similar to observations in spontaneously breathing animals, these results, demonstrate that during HF-SCS in C2 spinalized dogs: 1) airway occlusion results in compensatory increases in EI muscle activation, but not PA and 2) afferent inputs from muscle receptors, presumably muscle spindles, are a primary determinant of post-inspiratory EI activity. Conclusion: 1)Airway obstruction, duringHF-SCS to support ventilation in tetraplegic patients, may elicit compensatory increases in EI but not PA muscle activation and 2) post-inspiratory activity is mediated primarily by spinal afferents. National Institutes of Health grant no. R01 NS105785. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

ContextParalysis of the expiratory muscles in cervical and high thoracic spinal cord injury (SCI) results in an impaired ability to clear airway secretions effectively and increases the risk of atelectasis and respiratory tract infections (RTI). Spinal cord stimulation (SCS) applied via the Cough Stimulation System (CSS) has been shown to restore an effective cough mechanism in subjects with SCI. In this study, we evaluated the specific impact of use of the CSS by one study participant with SCI, subsequent discontinuation of usage, and then re-institution of this modality. Airway pressure generation (P) and peak expiratory airflow rate (F) achieved with CSS and clinical assessment questionnaires were assessed.FindingsWith the CSS, this subject was able to generate P and F rates of 103 cmH2O and 7.1 l/s, respectively, with associated significant clinical benefits, including, much greater ease in raising secretions and reduction in the incidence of RTIs. However, following a 2-year period of regular use, the CSS became non-functional and a 2-year period elapsed before it could be replaced. During this time, he again experienced great difficulty managing airway secretions and an increased frequency of RTIs. Re-institution of the CSS system resulted in the restoration of an effective cough mechanism and similar clinical benefits.Conclusion/Clinical RelevanceThis report demonstrates the very high degree of the clinical utility of the CSS as it had made a substantial beneficial impact on this participant's respiratory status and life quality.

Venom production has evolved independently many times in the animal kingdom, although it is rare among mammals. Venomous shrews produce venom in their submandibular salivary glands and use it for food acquisition. Only a few toxins have been identified in shrew venoms thus far, and their modes of action require investigation. The biological and molecular processes relating to venom production and gland functioning also remain unknown. To address this gap, we investigated protein content in extracts from venom glands of two shrew species, Neomys fodiens and Sorex araneus, and interpreted their biological functions. Applying a proteomic approach coupled with Gene Ontology enrichment analysis, we identified 313 and 187 putative proteins in venom glands of N. fodiens and S. araneus, respectively. A search of the UniProt database revealed that most of the proteins found in both shrew species were involved in metabolic processes and stress response, while GO enrichment analysis revealed more stress-related proteins in the glands of S. araneus. Molecules that regulate molecule synthesis, cell cycles, and cell divisions are necessary to enable venom regeneration and ensure its effectiveness in predation and food hoarding. The presence of proteins involved in stress response may be the result of shrews’ high metabolic rate and the costs of venom replenishment. Some proteins are likely to promote toxin spreading during envenomation and, due to their proteolytic action, reinforce venom toxicity. Finally, finding numerous proteins involved in immune response suggests a potential role of shrew venom gland secretions in protection against pathogens. These findings open up new perspectives for studying biological functions of molecules from shrew venom glands and extend our knowledge on the functioning of eulipotyphlan venom systems. Because the majority of existing and putative venomous mammals use oral venom systems to inject venom into target species, the methods presented here provide a promising avenue for confirming or discovering new taxa of venomous mammals.

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.

The efficiency of aposematic colouration of prey is based on the innate bias or facilitation of avoidance learning of predators. In many toxic bufonids, larvae are uniformly black, which is considered a warning signal. We compared fish predation on normal (black) and 'transient albino' (greyish) common toad Bufo bufo tadpoles that did not differ in toxicity or activity. In a two-stage experiment, each fish was presented with tadpoles of one colour in the first trial and the other colour in a subsequent trial. While tadpoles sampled by fish were typically not ingested, some died from injuries. The attack rate did not differ between tadpole phenotypes nor trials, irrespective of which phenotype was the first exposed to the fish. However, during the second trial, the sampled tadpoles, independent of colouration, were mouthed by fish for shorter periods and tadpole mortality decreased. The duration of mouthing also declined with an increasing number of attacks during subsequent trials. We conclude that in single-species prey populations, black tadpole colouration is not a warning signal as it does not accelerate predator learning about prey unprofitability. Our results indicate that with growing experience, predators sample potentially toxic prey more cautiously. This may explain why natural selection does not eliminate aposematic morphs even if predators continuously sample conspicuous prey.

BACKGROUND:Parotoid gland secretion of bufonid toads is a rich source of toxic molecules that are used against predators, parasites and pathogens. Bufadienolides and biogenic amines are the principal compounds responsible for toxicity of parotoid secretion. Many toxicological and pharmacological analyses of parotoid secretions have been performed, but little is known about the processes related to poison production and secretion. Therefore, our aim was to investigate protein content in parotoids of the common toad, Bufo bufo, to understand the processes that regulate synthesis and excretion of toxins as well as functioning of parotoid macroglands.RESULTS:Applying a proteomic approach we identified 162 proteins in the extract from toad's parotoids that were classified into 11 categories of biological functions. One-third (34.6%) of the identified molecules, including acyl-CoA-binding protein, actin, catalase, calmodulin, and enolases, were involved in cell metabolism. We found many proteins related to cell division and cell cycle regulation (12.0%; e.g. histone and tubulin), cell structure maintenance (8.4%; e.g. thymosin beta-4, tubulin), intra- and extracellular transport (8.4%), cell aging and apoptosis (7.3%; e.g. catalase and pyruvate kinase) as well as immune (7.0%; e.g. interleukin-24 and UV excision repair protein) and stress (6.3%; including heat shock proteins, peroxiredoxin-6 and superoxide dismutase) response. We also identified two proteins, phosphomevalonate kinase and isopentenyl-diphosphate delta-isomerase 1, that are involved in synthesis of cholesterol which is a precursor for bufadienolides biosynthesis. STRING protein-protein interaction network predicted for identified proteins showed that most proteins are related to metabolic processes, particularly glycolysis, stress response and DNA repair and replication. The results of GO enrichment and KEGG analyses are also consistent with these findings.CONCLUSION:This finding indicates that cholesterol may be synthesized in parotoids, and not only in the liver from which is then transferred through the bloodstream to the parotoid macroglands. Presence of proteins that regulate cell cycle, cell division, aging and apoptosis may indicate a high epithelial cell turnover in parotoids. Proteins protecting skin cells from DNA damage may help to minimize the harmful effects of UV radiation. Thus, our work extends our knowledge with new and important functions of parotoids, major glands involved in the bufonid chemical defence.

Background: High Frequency Spinal Cord Stimulation (HF-SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. Objective: To evaluate the pattern of diaphragm (D), parasternal (PA) and external intercostal (EI) activation during rectangular vs ramp-shape HF-SCS, compared to spontaneous breathing. Methods: In 8 anesthetized dogs, a stimulating disc electrode was positioned on the ventral surface of the spinal cord at the T2 level. Stimulus train duration for ramp-shape and rectangular HF-SCS was set at 1.3s since this duration approximated that occurring during spontaneous breathing. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes approximated that occurring during SB. The ramp-shape pattern of stimulation was linearly increased from zero to the desired stimulus amplitude. Single motor unit (SMU) EMG activity of the PA, EI and D muscles was assessed during SB and HF-SCS (following spinalization at the C2 level) with rectangular and ramp-shape stimulation patterns, in separate trials. Time of onset (To), b) time to peak discharge frequency (TTP) and c) peak firing frequency (PFF) were measured under each condition. To and TTP were determined relative to the onset of inspiratory flow and expressed as a percentage of inspiratory time (Ti). The patterns of the inspiratory muscle activation during HF-SCS were compared to that obtained during spontaneous breathing. Results: During SB, D was recruited first followed by PA and EI; mean ± SE To was 19.6±1.4, 32.1±2.4 and 40.4±2.3%Ti, respectively. During rectangular HF-SCS, To was 3.0±0.4, 5.8±1.2 and 4.3±0.9%Ti for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, To was 23.1±3.7, 33.6±4.5 and 39.9±4.6%Ti for D, PA and EI respectively (NS for each compared to SB). During SB, TTP was 65.2±2.2, 71.0±2.0 and 74.0±2.0%Ti for D, PA and EI. During rectangular HF-SCS, TTP was 30.4±3.7, 25.4±3.3 and 35.2±2.8%Ti, for D, PA and EI (p<0.05 for each compared to SB). During ramp-shape HF-SCS, TTP was 60.5±2.9, 58.2±2.7 and 62.6±6.0%Ti for Dia, PA and EI (p<0.05 for PA and EI compared to SB). During SB, PFF of SMUs of the D, PA and EI were 10.3±0.5, 12.8±0.4 and 12.2±0.7Hz, respectively. However, during rectangular HF-SCS, PFF were 14.0±0.6, 14.7±0.7 and 14.5±0.5Hz for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, PFF were 12.3±0.8, 13.8±0.9 and 12.6±1.2 for D, PA and EI, respectively (NS for each compared to SB). Conclusion: Activation of the inspiratory motoneuron pools via HF-SCS is receptive to different patterns of electrical stimulation.Ramp-shape HF-SCS compared to rectangular HF-SCS results in a more physiologic pattern of inspiratory muscle activation. National Institutes of Health grant no. R01 NS105785. Conflict of interest: Dr. A. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems (nos. 5,678,535 and 5,911,218). Dr. A. DiMarco and Dr. K. Kowalski hold the U.S. patents for technology related to the content of this study, Respiratory Muscle Activation by Spinal Cord Stimulation (no. 8,352,036). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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 cmH(2)O and 118 +/- 14 cmH(2)O, 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.

HF-SCS applied to support ventilation in high tetraplegics with airway obstruction may elicit compensatory increases in EI muscle activation. These results support the concept that spinal reflex effects remain functional during HF-SCS. The EI have a much higher density of muscle spindles compared to the PA muscles, which may mediate the differential activation of these muscles.

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.

Background Venom production has evolved independently many times in the animal kingdom, although it is rare among mammals. Venomous shrews produce toxins in their salivary glands and use their venoms to hunt and store prey. Thus far, the toxicity and composition of shrew venoms have been studied only in two shrew species: the northern short-tailed shrew, Blarina brevicauda , and the Eurasian water shrew, Neomys fodiens . Venom of N. fodiens has potent paralytic activity which enables hunting and storing prey in a comatose state. Here, we assayed the hemolytic effects of extracts from salivary glands of N. fodiens and the common shrew, Sorex araneus , in erythrocytes of Pelophylax sp. frogs. We identified toxins in shrew venom by high-performance liquid chromatography coupled to tandem mass spectrometry. Results Our results prove, confirming a suggestion made four centuries ago, that S. araneus is venomous. We also provide the first experimental evidence that shrew venoms produce potent hemolysis in frog erythrocytes. We found significant concentration-dependent effects of venoms of N. fodiens and S. araneus on hemolysis of red blood cells evaluated as hemoglobin release. Treatment of erythrocytes with N. fodiens venom at concentrations of 1.0 and 0.5 mg/ml and with S. araneus venom at concentration of 1.0 mg/ml caused an increased release of hemoglobin. Our findings confirm that hemolytic effects of N. fodiens venom are stronger than those produced by S. araneus venom. We identified four toxins in the venom of N. fodiens : proenkephalin, phospholipase A 2 (PLA 2 ), a disintegrin and metalloproteinase domain-containing protein (ADAM) and lysozyme C, as well as a non-toxic hyaluronidase. In the venom of S. araneus we found five toxins: proenkephalin, kallikrein 1-related peptidase, beta-defensin, ADAM and lysozyme C. PLA 2 and ADAMs are likely to produce hemolysis in frog erythrocytes. Conclusions Our results clearly show that shrew venoms possess hemolytic action that may allow them to hunt larger prey. Since a member of the numerous genus Sorex is venomous, it is likely that venom production among shrews and other eulipotyphlans may be more widespread than it has previously been assumed.

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.

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.

Venomousness is a complex functional trait that has evolved independently many times in the animal kingdom, although it is rare among mammals. Intriguingly, most venomous mammal species belong to Eulipotyphla (solenodons, shrews). This fact may be linked to their high metabolic rate and a nearly continuous demand of nutritious food, and thus it relates the venom functions to facilitation of their efficient foraging. While mammalian venoms have been investigated using biochemical and molecular assays, studies of their ecological functions have been neglected for a long time. Therefore, we provide here an overview of what is currently known about eulipotyphlan venoms, followed by a discussion of how these venoms might have evolved under ecological pressures related to food acquisition, ecological interactions, and defense and protection. We delineate six mutually nonexclusive functions of venom (prey hunting, food hoarding, food digestion, reducing intra- and interspecific conflicts, avoidance of predation risk, weapons in intraspecific competition) and a number of different subfunctions for eulipotyphlans, among which some are so far only hypothetical while others have some empirical confirmation. The functions resulting from the need for food acquisition seem to be the most important for solenodons and especially for shrews. We also present several hypotheses explaining why, despite so many potentially beneficial functions, venomousness is rare even among eulipotyphlans. The tentativeness of many of the arguments presented in this review highlights our main conclusion, i.e., insights regarding the functions of eulipotyphlan venoms merit additional study.

Venomous mammals are rare and their venoms have not been comprehensively investigated. Among shrews, only venoms of the short-tailed shrew Blarina brevicauda and the Eurasian water shrew Neomys fodiens have been characterized thus far. Neomys fodiens employs its venom to hunt on larger prey and store it in a comatose state. Recently, the potent paralytic activity of its venom has been confirmed. Here we assayed the hemolytic effects of crude extracts of salivary glands of N. fodiens and the common shrew Sorex araneus in the red blood cells of frog. Toxins present in saliva were identified by high-performance liquid chromatography coupled to tandem mass spectrometry. For both shrew species we found significant concentration-dependent effects of venom on hemolysis in erythrocytes evaluated as hemoglobin release. Hemolytic effects of N. fodiens saliva were stronger than those produced by S. araneus. We identified four toxins in N. fodiens venom and five in the saliva of S. araneus. Some of them are likely to produce hemolysis in frog’s erythrocytes. Our results show that shrew venoms, in addition to potent paralytic properties, possess also hemolytic activity that may allow them to hunt larger prey as frogs. Additionally, because S. araneus saliva exhibits toxic activity we propose to add the common shrew to the list of venomous mammals.

Background: Upper extremity (UE) pain/pathology is commonly reported in individuals with spinal cord injury (SCI); however, surveys account for much of the data and thus don't necessarily reflect frequency of diagnosis.Objective: The purpose of this study is to determine the first instance of clinically diagnosed UE pain/pathology in individuals with traumatic SCI in Olmsted County, MN. Design: A retrospective chart review was completed using a medical record linkage system (the Rochester Epidemiology Project (REP) for Olmsted County, MN and surrounding areas) and associated medical records dating 1976-2016.Methods: Potential subjects were identified with SCI diagnosis codes occurring during the study period, 1976-2016.Traumatic SCI was confirmed by searching the REP and medical records.Time following confirmed SCI and within the study period was reviewed in the REP to identify clinical diagnoses suggesting UE pain/pathology not directly related to the traumatic event leading to SCI.The medical record was reviewed to confirm a diagnosis of UE pain/pathology.Primary outcomes include: (1) proportion of individuals with traumatic SCI who had a confirmed UE pain/pathology diagnosis during the study period and (2) median pain-free time following SCI determined by Kaplan Meier survival analysis.Results observed: Eighty-two individuals were confirmed to have traumatic SCI (median age: 34 years [range 18-84], 77% male).SCI was classified by neurological level of injury (39% with paraplegia, 61% with tetraplegia) and ASIA impairment scale grade (32% A, 16% B, 17% C, 30% D, and 5% unable to determine).Median follow-up time available after SCI was 10.7 years (range: 1 week to 38.8 years).Fifty percent of the cohort had clinical diagnoses of UE pain/pathology during the available follow-up period.Median pain-free time was 7.7 years (95% CI:4.5-13.7).Conclusions: Results of this study demonstrate the importance of healthcare providers screening for UE pain/ pathology in patients with traumatic SCI.It additionally provides context for when patients are likely to start experiencing difficulty, which can guide both prevention and timely diagnosis.

ObjectiveTo compare the effectiveness of wire versus disc electrodes to activate the inspiratory muscles via high frequency spinal cord stimulation.DesignAnimal study.SettingResearch laboratory.AnimalsDogs (n = 5)InterventionsIn 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.ResultsTwo 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 ± 6 and 92 ± 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 ± 4 and 94 ± 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.

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.

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.