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.

Controlling the Polymorphism of Indomethacin with Poloxamer 407 in a Gas Antisolvent Crystallization Process.

The polymorphic control of active pharmaceutical ingredients (APIs) is a major challenge in the manufacture of medicines. Crystallization methods that use supercritical carbon dioxide as an antisolvent can create unique solid forms of APIs, with a particular tendency to generate metastable polymorphic forms. In this work, the effects of processing conditions within a gas antisolvent (GAS) crystallization method, such as pressure, stirring rate, and temperature, as well as the type of solvent used and the presence of an additive, on the polymorphism of indomethacin were studied. Consistent formation of the X-ray powder diffraction-pure α polymorphic form of indomethacin by GAS was only achieved when a polymer, poloxamer 407, was used as an additive. Using the GAS method in combination with poloxamer 407 as a molecular additive enabled full control over the polymorphic form of indomethacin, regardless of the processing conditions employed, such as pressure, temperature, stirring rate, and type of solvent. A detailed molecular modeling study provided insight into the role of poloxamer 407 in the polymorphic outcome of indomethacin and concluded that it favored the formation of the α polymorph.

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.

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 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.

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.

Herpes simplex reactivation following neurosurgery: case report and review of the literature.

Herpes simplex encephalitis is a common viral encephalitis associated with significant morbidity and mortality if not diagnosed and treated early. Neurosurgery may be an impetus for viral reactivation, either from direct nerve manipulation or high-dose steroids often administered during cases. The authors present the 40th known case of herpes simplex virus (HSV) encephalitis following neurosurgical intervention and review the previously reported cases. In their review, the authors observed positive HSV polymerase chain reaction (PCR), which had initially been negative in several cases. In cases in which there is high suspicion of HSV, it may be prudent to continue antiviral therapy and retest CSF for HSV PCR. Antiviral therapy significantly reduces mortality associated with HSV encephalitis.

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.

Contemporary Updates on Clinical Trials of Antiangiogenic Agents in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) has the highest rate of vascular proliferation among solid tumors. Angiogenesis is the central feature of rapid tumor growth in GBM and therefore remains an appealing therapeutic target in the treatment of these highly malignant tumors. Antiangiogenic therapy is emerging as an important adjuvant treatment. Multiple antiangiogenic agents targeting various sites in vascular endothelial growth factor (VEGF) and integrin pathways have been tested in clinical trials of newly diagnosed and recurrent GBMs. These include bevacizumab, enzastaurin, aflibercept, cediranib, and cilengitide. In this review, we discuss the current status and challenges facing clinical application of antiangiogenic treatment including anti-VEGF therapy and integrin pathway agents' therapy in glioblastoma. Here, we highlight a strong biologic rationale for this strategy, also focusing on integrin pathways. PubMed-indexed clinical trials published in English on antiangiogenic treatment of glioblastomas in the past 5 years were reviewed. The results of the current clinical trials of these agents are presented.

From Hypothermia to Cephalosomatic Anastomoses: The Legacy of Robert White (1926-2010) at Case Western Reserve University of Cleveland.

Dr. Robert J. White (1926-2010) was an eminent neurosurgeon and bioethicist, renowned for his classic work in hypothermia and pioneering mammalian head transplant experiments. He founded the Division of Neurosurgery at the Cleveland Metropolitan General Hospital (currently MetroHealth Medical Center, a level 1 trauma county hospital) and became the youngest full professor at the Case Western Reserve University in Cleveland, Ohio. With over 500 research articles to his credit, he founded the Brain Research Laboratory at what was then the Cleveland Metropolitan General Hospital, which was also home to future leaders in neurosurgery, neurosciences, and allied specialties. He transferred a healthy monkey head onto a surgically beheaded monkey body under deep hypothermic conditions drawing both laurels and criticisms alike. Despite a largely controversial neurosurgical research career, his original contributions to deep hypothermia have found profound clinical applications in modern trauma and vascular neurosurgery. The new fusogens and myelorrhaphy methods being tried in Europe hold promise for a future of reanastomosing 2 homologous or heterologous tracts in the neuraxis.

Case report: Minimally invasive method to activate the expiratory muscles to restore cough.

CONTEXT: Spinal cord stimulation (SCS) via disc electrodes surgically placed via laminotomy incisions has been shown to restore an effective cough in subjects with spinal cord injury (SCI). The purpose of this study was to evaluate a new method of expiratory muscle activation utilizing spinal cord wire leads, which can be implanted with minimally invasive techniques. METHODS: In a subject with SCI, parallel wire leads with two electrode contacts were inserted percutaneously through a needle, advanced to the T9, T11 spinal levels and connected to an implanted radiofrequency receiver. Stimulus parameters were set at values resulting in near maximum airway pressure generation (Paw) (40V, 50Hz, 0.2ms). Paw was measured at functional residual capacity (FRC) and total lung capacity (TLC) as an index of expiratory muscle strength. RESULTS: Paw during spontaneous efforts was 20 cmH2O (8.6% predicted). Bipolar (T9-T11) SCS resulted in Paw of 84 and 103 cmH2O, at FRC and TLC respectively. Monopolar (T9 only) SCS resulted in Paw of 61 and 86 cmH2O, at FRC and TLC respectively. This subject experienced much greater ease in raising secretions with use of SCS and no longer required other methods of secretion management. CONCLUSION: SCS via wire leads, which can be implanted using minimally invasive techniques, may provide a new useful method to restore an effective cough and possibly reduce the morbidity and mortality associated with respiratory tract infections in patients with SCI.

Economic Consequences of an Implanted Neuroprosthesis in Subjects with Spinal Cord Injury for Restoration of an Effective Cough.

Objective: To determine if an implanted neuroprosthesis for restoration of an effective cough is less costly than conventional methods of respiratory management. Methods: Nonrandomized clinical trial of participants (N = 14) with spinal cord injury (SCI) using the Cough Stimulator device in the inpatient hospital setting for Cough Stimulator implantation and outpatient hospital or residence for follow-up. A neuroprosthesis was implanted for restoration of an effective cough. The annual costs associated with respiratory management, without (pre implantation) and with (post implantation) the neuroprosthesis, were examined over a 4-year period. Results: The total cost related to implantation of the Cough Stimulator was $59,891, with no maintenance costs over subsequent years. The incidence of respiratory tract infections and the need for caregiver support fell significantly following implantation. The costs associated with respiratory tract infections fell significantly from a mean of $36,406 ± 11,855/year to $13,284 ± 7,035/year (p < .05) pre and post implantation, respectively. Costs fell further to $8,817 ± 5,990 and $4,467 ± 4,404 following the 2nd and 3rd years post implantation (p < .05), respectively. The costs associated with caregiver support fell significantly from $25,312 ± 8,019/year to $2,630 ± 2,233/year (p < .05) pre and post implantation, respectively, and remained low in subsequent years (p < .05). Other costs related to secretion management fell significantly and remained low in subsequent years (p < .05). Break-even analysis demonstrated that this point was reached in the first year. Conclusion: The results of this investigation demonstrate that implantation and use of the Cough Stimulator resulted in significant reductions in the overall costs of respiratory management in this patient population.

Ultrasound Guided Local Endovascular Coiling of an Iatrogenic Superficial Temporal Artery Pseudoaneurysm.

Pseudoaneurysms of the superficial temporal artery are rare and may be treated by manual compression, surgical intervention, coil embolization, or percutaneous thrombin injection. We present a novel technique of local ultrasound guided low-profile coil embolization of the superficial temporal artery with both satisfactory cosmetic and surgical results.

Holospinal epidural abscess of the spinal axis: two illustrative cases with review of treatment strategies and surgical techniques.

Despite the increasing prevalence of spinal infections, the subcategory of holospinal epidural abscesses (HEAs) is extremely infrequent and requires unique management. Panspinal imaging (preferably MRI), modern aggressive antibiotic therapy, and prompt surgical intervention remain the standard of care for all spinal axis infections including HEAs; however, the surgical decision making on timing and extent of the procedure still remain ill defined for HEAs. Decompression including skip laminectomies or laminoplasties is described, with varied clinical outcomes. In this review the authors present the illustrative cases of 2 patients with HEAs who were treated using skip laminectomies and epidural catheter irrigation techniques. The discussion highlights different management strategies including the role of conservative (nonsurgical) management in these lesions, especially with an already identified pathogen and the absence of mass effect on MRI or significant neurological defects. Among fewer than 25 case reports of HEA published in the past 25 years, the most important aspect in deciding a role for surgery is the neurological examination. Nearly 20% were treated successfully with medical therapy alone if neurologically intact. None of the reported cases had an associated cranial infection with HEA, because the dural adhesion around the foramen magnum prevented rostral spread of infection. Traditionally a posterior approach to the epidural space with irrigation is performed, unless an extensive focal ventral collection is causing cord compression. Surgical intervention for HEA should be an adjuvant treatment strategy for all acutely deteriorating patients, whereas aspiration of other infected sites like a psoas abscess can determine an infective pathogen, and appropriate antibiotic treatment may avoid surgical intervention in the neurologically intact patient.

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.

Extracranial ligation of ethmoidal arteries before resection of giant olfactory groove or planum sphenoidale meningiomas: 3 illustrative cases with a review of the literature on surgical techniques.

OBJECT: There are several surgical techniques for reducing blood loss-open surgical and endoscopic-prior to resection of giant anterior skull base meningiomas, especially when preoperative embolization is risky or not technically feasible. The authors present examples of an institutional experience using surgical ligation of the anterior and posterior ethmoidal arteries producing persistent tumor blush in partially embolized tumors. METHODS: The authors identified 12 patients who underwent extracranial surgical ligation of ethmoidal arteries through either a transcaruncular or a Lynch approach. Of these, 3 patients had giant olfactory groove or planum sphenoidale meningiomas. After approval from the institution privacy officer, the authors studied the medical records and imaging data of these 3 patients, with special attention to surgical technique and outcome. The variations of ethmoidal artery foramina pertaining to this surgical approach were studied using preserved human skulls from the Hamann-Todd Osteological Collection at the Museum of Natural History, Cleveland, Ohio. RESULTS: The extracranial ligation was performed successfully for control of the ethmoidal arteries prior to resection of hypervascular giant anterior skull base meningiomas. The surgical anatomy and landmarks for ethmoidal arteries were reviewed in anthropology specimens and available literature with reference to described surgical techniques. CONCLUSIONS: Extracranial surgical ligation of anterior, and often posterior, ethmoidal arteries prior to resection of large olfactory groove or planum sphenoidale meningiomas provides a safe and feasible option for control of these vessels prior to either open or endoscopic resection of nonembolized or partially embolized tumors.

Duplication of the pituitary gland associated with multiple blastogenesis defects: Duplication of the pituitary gland (DPG)-plus syndrome. Case report and review of literature.

BACKGROUND: Duplication of the pituitary gland (DPG) is a rare craniofacial developmental anomaly occurring during blastogenesis with postulated etiology such as incomplete twinning, teratogens, median cleft face syndrome or splitting of the notochord. The complex craniocaudal spectrum of blastogenesis defects associated with DPG is examined with an illustrative case. CASE DESCRIPTION: We report for the first time in the medical literature some unique associations with DPG, such as a clival encephalocele, third cerebral peduncle, duplicate odontoid process and a double tongue with independent volitional control. This patient also has the previously reported common associations such as duplicated sella, cleft palate, hypertelorism, callosal agenesis, hypothalamic enlargement, nasopharyngeal teratoma, fenestrated basilar artery and supernumerary teeth. This study also reviews 37 cases of DPG identified through MEDLINE literature search from 1880 to 2011. It provides a detailed analysis of the current case through physical examination and imaging. CONCLUSION: The authors propose that the developmental deformities associated with duplication of pituitary gland (DPG) occur as part of a developmental continuum, not as chance associations. Considering the fact that DPG is uniquely and certainly present throughout the spectrum of these blastogenesis defects, we suggest the term DPG-plus syndrome.

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.