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Wecht JM, Maher MT, Kirshblum SC, Escalon MX, Weir JP. Sit-up test to assess orthostatic hypotension in individuals with spinal cord injury. Clin Auton Res 2025; 35:393-405. [PMID: 40032720 DOI: 10.1007/s10286-024-01102-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 12/07/2024] [Indexed: 03/05/2025]
Abstract
AIM Individuals with spinal cord injury (SCI) have an increased prevalence of orthostatic hypotension (OH). Diagnosis of OH is made with active standing or tilt table testing, with limited the use in individuals with SCI. METHODS An alternative approach to assess OH is the sit-up test, which involves passive repositioning from the supine to the seated position. The purpose of this study was to document the reliability and validity of the sit-up test, and determine whether the level or severity of injury related to orthostatic blood pressure (BP) responses in a large, diverse group of individuals with SCI. RESULTS A total of 166 participants-119 individuals with SCI and 47 uninjured control-completed two sit-up tests, and 36 individuals who completed the sit-up tests also underwent a head-up tilt test. Change in BP from sit-up test 1 to sit-up test 2 was not significantly different for either systolic BP or diastolic BP. Neither level nor severity of injury contributed to the reliability assessments, which showed disappointing results with generally low interclass correlation coefficients (ICC), with values ranging from 0 to 0.63, and large standard error of measurements (SEM), ranging from 5.2 to 13.7 mmHg. Comparison between BP responses to the sit-up test and the head-up tilt showed good sensitivity and specificity, with positive predictive values > 75%. CONCLUSION Prevalent BP instability likely contributed to the poor reliability of the sit-up test, but the test is easy to perform with a high likelihood ratio for the valid assessment of OH in individuals with SCI. CLINICAL TRIAL REGISTRATION NCT01758692.
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Affiliation(s)
- Jill M Wecht
- James J Peters VA Medical Center, Room 7A-13, 130 W Kingsbridge Road, Bronx, NY, 10468, USA.
- Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Matthew T Maher
- James J Peters VA Medical Center, Room 7A-13, 130 W Kingsbridge Road, Bronx, NY, 10468, USA
- Kessler Foundation at the Kessler Institute for Rehabilitation, West Orange, NJ, USA
| | - Steven C Kirshblum
- Kessler Foundation at the Kessler Institute for Rehabilitation, West Orange, NJ, USA
- Rutgers New Jersey Medical School, Newark, NJ, USA
| | | | - Joseph P Weir
- James J Peters VA Medical Center, Room 7A-13, 130 W Kingsbridge Road, Bronx, NY, 10468, USA
- University of Kansas, Lawrence, KS, USA
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Yi Lau SJ, Hang PZ, Lijia W, Jing C. Effective management of orthostatic hypotension in a patient with complete spinal cord injury using a portable transcutaneous spinal cord stimulation device: A case report. J Spinal Cord Med 2025:1-5. [PMID: 40358400 DOI: 10.1080/10790268.2025.2496566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025] Open
Abstract
CONTEXT Orthostatic hypotension (OH) is a debilitating condition in spinal cord injury (SCI) patients, characterized by impaired autonomic regulation and significant drops in blood pressure (BP) upon upright positioning. Despite pharmacological and non-pharmacological interventions, OH often persists, limiting rehabilitation progression and daily functional activities. Transcutaneous spinal cord stimulation (tSCS), is a non-invasive modality that has shown promise in addressing cardiovascular dysregulation. However, clinical application of tSCS is often constrained by availability. FINDINGS This case report describes a novel application of a commercially available neuromuscular electrical stimulation (NMES) device, adapted for transcutaneous spinal cord stimulation, in a 49-year-old male with C5 complete SCI and severe OH refractory to conventional treatments. The intervention demonstrated immediate stabilization of BP and symptom resolution during upright positioning, enabling significant functional gains, including improved sitting tolerance and enhanced quality of life. CONCLUSION These findings suggest that NMES can be a cost-effective and portable alternative to traditional tSCS, and may broaden therapeutic options for managing OH in SCI patients. Further research is warranted to validate these results and optimize its clinical application.
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Affiliation(s)
- Sandra Jia Yi Lau
- Department of Rehabilitation Medicine, Singapore General Hospital Singapore, Singapore
| | - Pan Zi Hang
- Department of Rehabilitation Medicine, Singapore General Hospital Singapore, Singapore
| | - Wu Lijia
- Department of Specialty Nursing, Singapore General Hospital, Singapore, Singapore
| | - Chen Jing
- Department of Rehabilitation Medicine, Singapore General Hospital Singapore, Singapore
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3
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Sato T, Kimura R, Kasukawa Y, Kudo D, Hatakeyama K, Watanabe M, Takahashi Y, Okura K, Suda T, Miyamoto D, Iwami T, Miyakoshi N. Effects of Gait Rehabilitation Robot Combined with Electrical Stimulation on Spinal Cord Injury Patients' Blood Pressure. SENSORS (BASEL, SWITZERLAND) 2025; 25:984. [PMID: 39943623 PMCID: PMC11819915 DOI: 10.3390/s25030984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/13/2025] [Accepted: 02/03/2025] [Indexed: 02/16/2025]
Abstract
BACKGROUND Orthostatic hypotension can occur during acute spinal cord injury (SCI) and subsequently persist. We investigated whether a gait rehabilitation robot combined with functional electrical stimulation (FES) stabilizes hemodynamics during orthostatic stress in SCI. METHODS Six intermediate-phase SCI patients (five males and one female; mean age: 49.5 years; four with quadriplegia and two with paraplegia) participated. The participants underwent robotic training (RT), with a gait rehabilitation robot combined with FES, and tilt table training (TT). Hemodynamics were monitored using a laser Doppler flowmeter for the earlobe blood flow (EBF) and non-invasive blood pressure measurements. The EBF over time and the resting and exercise blood pressures were compared between each session. Adverse events were also evaluated. RESULTS The EBF change decreased in TT but increased in RT at the 0.5-min slope (p = 0.03). Similarly, the pulse rate change increased in TT but decreased in RT at the 1-min slope (p = 0.03). Systolic and mean blood pressures were slightly higher in RT than in TT but not significantly (p = 0.35; 0.40). No adverse events occurred in RT, but two TT sessions were incomplete due to dizziness. CONCLUSIONS RT with FES can reduce symptoms during orthostatic stress in intermediate-phase SCI. Future studies require a larger number of cases to generalize this study.
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Affiliation(s)
- Takahiro Sato
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; (T.S.); (N.M.)
| | - Ryota Kimura
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; (T.S.); (N.M.)
| | - Yuji Kasukawa
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Daisuke Kudo
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Kazutoshi Hatakeyama
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Motoyuki Watanabe
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Yusuke Takahashi
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Kazuki Okura
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Tomohiro Suda
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Daido Miyamoto
- Division of Rehabilitation Medicine, Akita University Hospital, 44-2, Hiroomote Hasunuma, Akita 010-8543, Japan; (Y.K.); (D.K.); (K.H.); (M.W.); (Y.T.); (K.O.); (T.S.); (D.M.)
| | - Takehiro Iwami
- Department of Systems Design Engineering, Faculty of Engineering Science, Akita University Graduate School of Engineering Science, 1-1 Tegata Gakuen-cho, Akita 010-8502, Japan;
| | - Naohisa Miyakoshi
- Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; (T.S.); (N.M.)
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Cao L, Yan WH, Pi W, Zhang Y, Xiong YX, Yong VW, Xue M, Li Q, Zheng C, Yang L. GABA B receptors regulate the neural stem cell potential of Pkd2l1 + cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway. Brain Res Bull 2025; 221:111217. [PMID: 39842645 DOI: 10.1016/j.brainresbull.2025.111217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/08/2024] [Accepted: 01/17/2025] [Indexed: 01/24/2025]
Abstract
Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABAB receptors (GABABRs) are expressed in Pkd2l1+ CSF-cNs. However, their role in Pkd2l1+ CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABABR expression in a murine model 7 d after SCI. We further discovered that GABABR activation enhanced the proliferation of Pkd2l1+ CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABABR primed quiescent Pkd2l1+ CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABABR activation enhances the NSC potential of Pkd2l1+ CSF-cNs, ultimately enabling post-SCI recovery in murine models.
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Affiliation(s)
- Liang Cao
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China
| | - Wei-Hong Yan
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Wenjun Pi
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yi Zhang
- Shunyi Maternal and Children's Hospital of Beijing Children's Hospital, Beijing, China
| | - Yan-Xiang Xiong
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - V Wee Yong
- Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
| | - Mengzhou Xue
- Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China
| | - Qing Li
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
| | - Chunfu Zheng
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
| | - Leiluo Yang
- Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
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Bojanic T, McCaughey EJ, Finn HT, Humburg P, McBain RA, Lee BB, Gandevia SC, Boswell-Ruys CL, Butler JE. The effect of abdominal functional electrical stimulation on blood pressure in people with high level spinal cord injury. Spinal Cord 2025; 63:31-37. [PMID: 39487221 DOI: 10.1038/s41393-024-01046-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/16/2024] [Accepted: 10/17/2024] [Indexed: 11/04/2024]
Abstract
STUDY DESIGN Single centre training study. OBJECTIVES To investigate, in a group of people with spinal cord injury (SCI), the effect of transcutaneous functional electrical stimulation of the abdominal muscles (abdominal FES) during cough training on blood pressure (BP), and how it is affected by injury characteristics and alters over time. SETTING Laboratory and community. METHODS Sixteen participants with SCI (C4-T5) underwent 25 of abdominal FES cough training (5 sets of 10 stimulated coughs) over 6 weeks as part of a previously published study on the effect of abdominal FES training on cough. Systolic BP (SBP), diastolic BP (DBP) and calculated mean arterial pressure (MAP) were measured at the completion of each set. RESULTS Abdominal FES coughing resulted in an average ~30% acute increase in BP from initial resting BP across all sessions in almost all participants (p < 0.001). However, the increase in BP during abdominal FES coughs from rest reduced over the 25 sessions of training by ~35% for SBP, MAP and DBP (p = 0.024, p = 0.013 and p = 0.042, respectively). There was no meaningful change in resting BP over time (p = 0.935, p = 0.705 and p = 0.988, respectively). Overall, increases in BP during abdominal FES coughs were greatest for those with chronic injuries and cervical injuries. CONCLUSIONS Transcutaneous abdominal FES during cough training acutely increases BP. However, the magnitude of the increase is reduced after 25 sessions of training. Abdominal FES may offer a solution to combat orthostatic hypotension, but its effectiveness may diminish over time.
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Affiliation(s)
- Teodora Bojanic
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
| | - Euan J McCaughey
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
- Queen Elizabeth National Spinal Injuries Unit, Queen Elizabeth University Hospital, Glasgow, G51 4TF, Scotland, UK
| | - Harrison T Finn
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
| | - Peter Humburg
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
| | - Rachel A McBain
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
| | - Bonsan B Lee
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
- Prince of Wales Hospital, Randwick, NSW, 2031, Australia
| | - Simon C Gandevia
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
- Prince of Wales Hospital, Randwick, NSW, 2031, Australia
| | - Claire L Boswell-Ruys
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- University of New South Wales, Kensington, NSW, 2052, Australia
- Prince of Wales Hospital, Randwick, NSW, 2031, Australia
| | - Jane E Butler
- Spinal Cord Injury Research Centre, Neuroscience Research Australia, Randwick, NSW, 2031, Australia.
- University of New South Wales, Kensington, NSW, 2052, Australia.
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Balbinot G, Milosevic M, Morshead CM, Iwasa SN, Zariffa J, Milosevic L, Valiante TA, Hoffer JA, Popovic MR. The mechanisms of electrical neuromodulation. J Physiol 2025; 603:247-284. [PMID: 39740777 DOI: 10.1113/jp286205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 11/20/2024] [Indexed: 01/02/2025] Open
Abstract
The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour. Here we examine the neural mechanisms that are thought to underlie the therapeutic effects seen with current neuromodulation technologies. To gain further insights into the mechanisms associated with electrical stimulation, we summarize recent findings from genetic dissection studies conducted in animal models. KEY POINTS: Electricity is everywhere around us and is essential for how our nerves communicate within our bodies. When nerves are damaged or not working properly, using exogenous electricity can help improve their function at distinct levels - inside individual cells, within neural circuits, and across entire systems. This method can be tailored to target specific types of cells, nerve fibres, neurotransmitters and communication pathways, offering significant therapeutic potential. This overview explains how exogenous electricity affects nerve function and its potential benefits, based on research in animal studies. Understanding these effects is important because electrical neuromodulation plays a key role in medical treatments for neurological conditions.
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Affiliation(s)
- Gustavo Balbinot
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- Institute for Neuroscience and Neurotechnology, Simon Fraser University, Burnaby, BC, Canada
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
| | - Matija Milosevic
- The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA
- Department of Neurological Surgery, University of Miami, Miami, FL, USA
- Department of Biomedical Engineering, University of Miami, Miami, FL, USA
| | - Cindi M Morshead
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
- KITE Research Institute - University Health Network, Toronto, ON, Canada
- Division of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada
- The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada
| | - Stephanie N Iwasa
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
- KITE Research Institute - University Health Network, Toronto, ON, Canada
| | - Jose Zariffa
- KITE Research Institute - University Health Network, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada
| | - Luka Milosevic
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
- KITE Research Institute - University Health Network, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Krembil Research Institute, University Health Network, Toronto, ON, Canada
| | - Taufik A Valiante
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
- KITE Research Institute - University Health Network, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada
| | - Joaquín Andrés Hoffer
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
| | - Milos R Popovic
- Center for Advancing Neurotechnological Innovation to Application - CRANIA, University Health Network, Toronto, ON, Canada
- KITE Research Institute - University Health Network, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada
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Zhao F, Balthazaar S, Hiremath SV, Nightingale TE, Panza GS. Enhancing Spinal Cord Injury Care: Using Wearable Technologies for Physical Activity, Sleep, and Cardiovascular Health. Arch Phys Med Rehabil 2024; 105:1997-2007. [PMID: 38972475 DOI: 10.1016/j.apmr.2024.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 06/13/2024] [Accepted: 06/24/2024] [Indexed: 07/09/2024]
Abstract
Wearable devices have the potential to advance health care by enabling real-time monitoring of biobehavioral data and facilitating the management of an individual's health conditions. Individuals living with spinal cord injury (SCI) have impaired motor function, which results in deconditioning and worsening cardiovascular health outcomes. Wearable devices may promote physical activity and allow the monitoring of secondary complications associated with SCI, potentially improving motor function, sleep, and cardiovascular health. However, several challenges remain to optimize the application of wearable technologies within this population. One is striking a balance between research-grade and consumer-grade devices in terms of cost, accessibility, and validity. Additionally, limited literature supports the validity and use of wearable technology in monitoring cardio-autonomic and sleep outcomes for individuals with SCI. Future directions include conducting performance evaluations of wearable devices to precisely capture the additional variation in movement and physiological parameters seen in those with SCI. Moreover, efforts to make the devices small, lightweight, and inexpensive for consumer ease of use may affect those with severe motor impairments. Overcoming these challenges holds the potential for wearable devices to help individuals living with SCI receive timely feedback to manage their health conditions and help clinicians gather comprehensive patient health information to aid in diagnosis and treatment.
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Affiliation(s)
- Fei Zhao
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI; John D. Dingell VA Medical Center, Research and Development, Detroit, MI
| | - Shane Balthazaar
- School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada; Department of Cardiology, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Shivayogi V Hiremath
- Department of Health and Rehabilitation Sciences, Temple University, Philadelphia, PA
| | - Tom E Nightingale
- School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.
| | - Gino S Panza
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI; John D. Dingell VA Medical Center, Research and Development, Detroit, MI.
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Trueblood CT, Singh A, Cusimano MA, Hou S. Autonomic Dysreflexia in Spinal Cord Injury: Mechanisms and Prospective Therapeutic Targets. Neuroscientist 2024; 30:597-611. [PMID: 38084412 PMCID: PMC11166887 DOI: 10.1177/10738584231217455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2024]
Abstract
High-level spinal cord injury (SCI) often results in cardiovascular dysfunction, especially the development of autonomic dysreflexia. This disorder, characterized as an episode of hypertension accompanied by bradycardia in response to visceral or somatic stimuli, causes substantial discomfort and potentially life-threatening symptoms. The neural mechanisms underlying this dysautonomia include a loss of supraspinal control to spinal sympathetic neurons, maladaptive plasticity of sensory inputs and propriospinal interneurons, and excessive discharge of sympathetic preganglionic neurons. While neural control of cardiovascular function is largely disrupted after SCI, the renin-angiotensin system (RAS), which mediates blood pressure through hormonal mechanisms, is up-regulated after injury. Whether the RAS engages in autonomic dysreflexia, however, is still controversial. Regarding therapeutics, transplantation of embryonic presympathetic neurons, collected from the brainstem or more specific raphe regions, into the injured spinal cord may reestablish supraspinal regulation of sympathetic activity for cardiovascular improvement. This treatment reduces the occurrence of spontaneous autonomic dysreflexia and the severity of artificially triggered dysreflexic responses in rodent SCI models. Though transplanting early-stage neurons improves neural regulation of blood pressure, hormonal regulation remains high and baroreflex dysfunction persists. Therefore, cell transplantation combined with selected RAS inhibition may enhance neuroendocrine homeostasis for cardiovascular recovery after SCI.
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Affiliation(s)
- Cameron T. Trueblood
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, USA
| | - Anurag Singh
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, USA
| | - Marissa A. Cusimano
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, USA
| | - Shaoping Hou
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, USA
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9
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Law M, Sachdeva R, Darrow D, Krassioukov A. Cardiovascular Effects of Spinal Cord Stimulation: The Highs, the Lows, and the Don't Knows. Neuromodulation 2024; 27:1164-1176. [PMID: 37665302 DOI: 10.1016/j.neurom.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/31/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023]
Abstract
BACKGROUND AND OBJECTIVES There are many potential etiologies of impaired cardiovascular control, from chronic stress to neurodegenerative conditions or central nervous system lesions. Since 1959, spinal cord stimulation (SCS) has been reported to modulate blood pressure (BP), heart rate (HR), and HR variability (HRV), yet the specific stimulation sites and parameters to induce a targeted cardiovascular (CV) change for mitigating abnormal hemodynamics remain unclear. To investigate the ability and parameters of SCS to modulate the CV, we reviewed clinical studies using SCS with reported HR, BP, or HRV findings. MATERIALS AND METHODS A keyword-based electronic search was conducted through MEDLINE, Embase, and PubMed data bases, last searched on February 3, 2023. Inclusion criteria were studies with human participants receiving SCS with comparison with SCS turned off, with reporting of either HR, HRV, or BP findings. Non-English studies, conference abstracts, and studies not reporting standalone effects of SCS when comparing SCS with non-SCS interventions were excluded. Results were plotted for visual analysis. When available, participant-specific stimulation parameters and effects were extracted and quantitatively analyzed using ordinary least squares regression. RESULTS A total of 59 studies were included in this review; 51 studies delivered SCS invasively through implanted/percutaneous leads. Eight studies used noninvasive, transcutaneous electrodes. We found numerous reports of cervical, high thoracic, and mid-to-low thoracolumbar SCS increasing resting BP, and cervical/mid-to-low thoracolumbar SCS decreasing BP. The effect of SCS location on HR and HRV was equivocal. We were unable to analyze stimulation parameters owing to inadequate parameter reporting in many publications. CONCLUSIONS Our findings suggest CV neuromodulation, particularly BP modulation, with SCS to be a promising frontier. Further research with larger randomized controlled trials and detailed reporting of SCS parameters will be necessary for appropriate evaluation of SCS as a CV therapy.
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Affiliation(s)
- Marco Law
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Rahul Sachdeva
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
| | - David Darrow
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, USA; Division of Neurosurgery, Hennepin County Medical Center, Minneapolis, MN, USA
| | - Andrei Krassioukov
- International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada; G.F. Strong Rehabilitation Centre, Vancouver Coastal Health, Vancouver, BC, Canada
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10
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Engel-Haber E, Bheemreddy A, Bayram MB, Ravi M, Zhang F, Su H, Kirshblum S, Forrest GF. Neuromodulation in Spinal Cord Injury Using Transcutaneous Spinal Stimulation-Mapping for a Blood Pressure Response: A Case Series. Neurotrauma Rep 2024; 5:845-856. [PMID: 39391052 PMCID: PMC11462428 DOI: 10.1089/neur.2024.0066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2024] Open
Abstract
Spinal cord transcutaneous stimulation (scTS) offers a promising approach to enhance cardiovascular regulation in individuals with a high-level spinal cord injury (SCI), addressing the challenges of unstable blood pressure (BP) and the accompanying hypo- and hypertensive events. While scTS offers flexibility in stimulation locations, it also leads to significant variability and lack of validation in stimulation sites utilized by studies. Our study presents findings from a case series involving eight individuals with chronic cervical SCI, examining the hemodynamic effects of scTS applied in different vertebral locations, spanning from high cervical to sacral regions. Stimulation of the lumbosacral vertebrae region (L1/2, S1/2, and also including T11/12) significantly elevated BP, unlike cervical or upper thoracic stimulation. The observed trend, which remained consistent across different participants, highlights the promising role of lumbosacral stimulation in neuromodulating BP.
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Affiliation(s)
- Einat Engel-Haber
- Kessler Foundation, West Orange, New Jersey, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | | | - Mehmed Bugrahan Bayram
- Kessler Foundation, West Orange, New Jersey, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | | | - Fan Zhang
- Kessler Foundation, West Orange, New Jersey, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Haiyan Su
- School of Computing, Montclair State University, Montclair, New Jersey, USA
| | - Steven Kirshblum
- Kessler Foundation, West Orange, New Jersey, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA
- Kessler Institute for Rehabilitation, West Orange, New Jersey, USA
| | - Gail F. Forrest
- Kessler Foundation, West Orange, New Jersey, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, New Jersey, USA
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11
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Mollà-Casanova S, Muñoz-Gómez E, Aguilar-Rodríguez M, Inglés M, Sempere-Rubio N, Moreno-Segura N, Serra-Añó P. Effectiveness of virtual-walking intervention combined with exercise on improving pain and function in incomplete spinal cord injury: a feasibility study. Spinal Cord Ser Cases 2024; 10:64. [PMID: 39174519 PMCID: PMC11341745 DOI: 10.1038/s41394-024-00675-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/07/2024] [Accepted: 08/13/2024] [Indexed: 08/24/2024] Open
Abstract
STUDY DESIGN A feasibility pilot study. OBJECTIVE To assess the feasibility a full-scale Randomized Controlled Trial aimed at assessing the beneficial effect of a Virtual Walking (VW)-based (Experimental intervention (EI)) on neuropathic pain and functionality in people with incomplete spinal cord injury (SCI). SETTING A hospital service (Hospital Universitario y Politécnico La Fe) and disability associations (TetraSport, CODIFIVA and ASPAYM). METHODS Twelve people with chronic incomplete SCI were randomized to EI (VW plus therapeutic exercise program (TE)) -or Control Intervention (CI (placebo VW and TE)) groups. A six-week intervention (3 sessions/week) was carried out. To assess feasibility, the following outcomes were used: level of restriction and validity of inclusion and exclusion criteria, participants' compliance, accessibility and acceptability of the intervention for participants, adequate pre-training time of physiotherapists. To explore therapy effectiveness, pain severity, and interference, mean and maximum isometric strength, walking speed, and walking ability were assessed before (Time 1, T1) and after (Time 2, T2) the intervention. RESULTS 20% of the participants initially recruited did not meet inclusion criteria. In addition, all participants completed at least 80% of the intervention sessions and none of the participants dropped out before T2. No serious adverse event was found. Moreover, 91.67% of participants were willing to perform the intervention again and all therapists involved were adequately pre-trained. Finally, our preliminary results suggest that the proposed EI is effective. CONCLUSION A full-scale RCT is feasible and preliminary results suggest that VW with TE could have a beneficial impact on pain and functionality in this population.
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Affiliation(s)
- Sara Mollà-Casanova
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
| | - Elena Muñoz-Gómez
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
| | - Marta Aguilar-Rodríguez
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
| | - Marta Inglés
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
| | - Núria Sempere-Rubio
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain.
| | - Noemí Moreno-Segura
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
| | - Pilar Serra-Añó
- UBIC research group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, Valencia, Spain
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12
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Wecht JM, Weir JP, Huang V, Escalon MX, Bryce TN. Treatment of Orthostatic Hypotension During Acute Inpatient Rehabilitation After Spinal Cord Injury: Usual Care vs. Anti-hypotensive Therapy. Am J Hypertens 2024; 37:554-560. [PMID: 38712567 DOI: 10.1093/ajh/hpae057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/02/2024] [Accepted: 04/30/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND To compare the pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). METHODS Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5), and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?" Study participants and therapists were unaware of the group assignment. RESULTS A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT, and 17 in the UC group. There was an average of 81 ± 51 therapy sessions/participant in the TXT and 60 ± 27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9 ± 8 sessions/participant in the TXT group and 10 ± 12 sessions/participant in the UC group. Neither the total number of therapy sessions (P = 0.16) nor group assignment (P = 0.83) significantly predicted the number of sessions affected by low BP. CONCLUSIONS These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to UC treatment of symptomatic hypotension and OH in newly injured patients with SCI. CLINICAL TRIALS REGISTRATION #NCT02919917.
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Affiliation(s)
- Jill M Wecht
- Spinal Cord Damage Research Center, James J. Peters VA Medical Center, Bronx, New York, USA
- Department of Rehabilitation and Human Performance, the Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Medicine, the Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Joseph P Weir
- Department of Health, Sport, and Exercise Sciences, University of Kansas, Lawrence, Kansas, USA
| | - Vincent Huang
- Department of Rehabilitation and Human Performance, the Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Miguel X Escalon
- Department of Rehabilitation and Human Performance, the Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Thomas N Bryce
- Department of Rehabilitation and Human Performance, the Icahn School of Medicine at Mount Sinai, New York, New York, USA
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13
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Ji W, Nightingale TE, Zhao F, Fritz NE, Phillips AA, Sisto SA, Nash MS, Badr MS, Wecht JM, Mateika JH, Panza GS. The Clinical Relevance of Autonomic Dysfunction, Cerebral Hemodynamics, and Sleep Interactions in Individuals Living With SCI. Arch Phys Med Rehabil 2024; 105:166-176. [PMID: 37625532 DOI: 10.1016/j.apmr.2023.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/25/2023] [Accepted: 08/06/2023] [Indexed: 08/27/2023]
Abstract
A myriad of physiological impairments is seen in individuals after a spinal cord injury (SCI). These include altered autonomic function, cerebral hemodynamics, and sleep. These physiological systems are interconnected and likely insidiously interact leading to secondary complications. These impairments negatively influence quality of life. A comprehensive review of these systems, and their interplay, may improve clinical treatment and the rehabilitation plan of individuals living with SCI. Thus, these physiological measures should receive more clinical consideration. This special communication introduces the under investigated autonomic dysfunction, cerebral hemodynamics, and sleep disorders in people with SCI to stakeholders involved in SCI rehabilitation. We also discuss the linkage between autonomic dysfunction, cerebral hemodynamics, and sleep disorders and some secondary outcomes are discussed. Recent evidence is synthesized to make clinical recommendations on the assessment and potential management of important autonomic, cerebral hemodynamics, and sleep-related dysfunction in people with SCI. Finally, a few recommendations for clinicians and researchers are provided.
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Affiliation(s)
- Wenjie Ji
- Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY
| | - Tom E Nightingale
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Trauma Science Research, University of Birmingham, Birmingham, UK; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada
| | - Fei Zhao
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI; John D. Dingell VA Medical Center, Research and Development, Detroit, MI
| | - Nora E Fritz
- Department of Health Care Sciences, Program of Physical Therapy, Detroit, MI; Department of Neurology, Wayne State University, Detroit, MI
| | - Aaron A Phillips
- Department of Physiology and Pharmacology, Cardiac Sciences, Clinical Neurosciences, Biomedical Engineering, Libin Cardiovascular institute, Hotchkiss Brain Institute, Cumming School of Medicine, Calgary, AB, Canada; RESTORE.network, University of Calgary, Calgary, AB, Canad
| | - Sue Ann Sisto
- Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY
| | - Mark S Nash
- Department of Neurological Surgery, Physical Medicine & Rehabilitation Physical Therapy, Miami, FL; Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL
| | - M Safwan Badr
- John D. Dingell VA Medical Center, Research and Development, Detroit, MI; Departments of Physiology and Internal Medicine, Wayne State University, Detroit, MI
| | - Jill M Wecht
- James J Peters VA Medical Center, Department of Spinal Cord Injury Research, Bronx, NY; Icahn School of Medicine Mount Sinai, Departments of Rehabilitation and Human Performance, and Medicine Performance, and Medicine, New York, NY
| | - Jason H Mateika
- John D. Dingell VA Medical Center, Research and Development, Detroit, MI; Departments of Physiology and Internal Medicine, Wayne State University, Detroit, MI
| | - Gino S Panza
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI; John D. Dingell VA Medical Center, Research and Development, Detroit, MI.
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14
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Jesuthasan A, Lim PB, Desai M, Dani M. The power of positioning: managing severe autonomic dysreflexia. Neurol Sci 2023; 44:4143-4146. [PMID: 37382730 DOI: 10.1007/s10072-023-06930-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 06/24/2023] [Indexed: 06/30/2023]
Affiliation(s)
- Aaron Jesuthasan
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 OHS, UK.
| | - Phang Boon Lim
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 OHS, UK
| | - Manish Desai
- Royal National Orthopaedic Hospital, Royal National Orthopaedic Hospital NHS Trust, Brockley Hill, Stanmore, HA7 4LP, UK
| | - Melanie Dani
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 OHS, UK
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15
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Mundra A, Varma Kalidindi K, Chhabra HS, Manghwani J. Spinal cord stimulation for spinal cord injury - Where do we stand? A narrative review. J Clin Orthop Trauma 2023; 43:102210. [PMID: 37663171 PMCID: PMC10470322 DOI: 10.1016/j.jcot.2023.102210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 05/14/2023] [Accepted: 06/29/2023] [Indexed: 09/05/2023] Open
Abstract
Recovery of function following a complete spinal cord injury (SCI) or an incomplete SCI where recovery has plateaued still eludes us despite extensive research. Epidural spinal cord stimulation (SCS) was initially used for managing neuropathic pain. It has subsequently demonstrated improvement in motor function in otherwise non-recovering chronic spinal cord injury in animal and human trials. The mechanisms of how it is precisely effective in doing so will need further research, which would help refine the technology for broader application. Transcutaneous spinal cord stimulation (TSCS) is also emerging as a modality to improve the functional outcome in SCI individuals, especially when coupled with appropriate rehabilitation. Apart from motor recovery, ESCS and TSCS have also shown improvement in autonomic, metabolic, genitourinary, and pulmonary function. Since the literature on this is still in its infancy, with no large-scale randomised trials and different studies using different protocols in a wide range of patients, a review of the present literature is imperative to better understand the latest developments in this field. This article examines the existing literature on the use of SCS for SCI individuals with the purpose of enabling functional recovery. It also examines the voids in the present research, thus providing future directions.
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Affiliation(s)
- Anuj Mundra
- Department of Spine and Rehabilitation, Sri Balaji Action Medical Institute, New Delhi, 110063, India
| | | | - Harvinder Singh Chhabra
- Department of Spine and Rehabilitation, Sri Balaji Action Medical Institute, New Delhi, 110063, India
| | - Jitesh Manghwani
- Indian Spinal Injuries Centre, Vasant Kunj, New Delhi, 110070, India
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16
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Takano M, Iida T, Hikata T. Persistent Orthostatic Hypotension Following Surgery for Adult Spinal Deformity: Prevalence, Risk Factors, and Cardiovascular Evaluation. Asian Spine J 2023; 17:685-692. [PMID: 37408295 PMCID: PMC10460655 DOI: 10.31616/asj.2022.0296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 12/05/2022] [Accepted: 12/15/2022] [Indexed: 07/07/2023] Open
Abstract
STUDY DESIGN Retrospective case-control study. PURPOSE To understand the prevalence of persistent orthostatic hypotension (POH), as well as its risk factors and cardiovascular pathology, in patients receiving surgery for the adult spinal deformity (ASD). OVERVIEW OF LITERATURE Although reports of the incidence of and risk factors for POH in different spinal disorders have recently been published, we are not aware of the comprehensive evaluation of POH following surgery for ASD. METHODS We examined medical records from a single central database for 65 patients receiving surgical treatment for ASD. Statistical comparisons were made between patients who experienced postoperative POH and those who did not, by examining patient and operative characteristics, such as age, sex, comorbidities, functional status, preoperative neurological function, vertebral fractures, three-column osteotomy, total operative time, estimated blood loss, length of stay, and radiographic parameters. The determinants of POH were assessed using multiple logistic regression. RESULTS We showed that postoperative POH was a complication of ASD surgery, with a 9% incidence rate. Patients with POH were statistically considerably more likely to require supported walkers due to partial paralysis and to have comorbidities including diabetes and neurodegenerative disease (ND). Furthermore, ND was an independent risk factor for postoperative POH (odds ratio, 4.073; 95% confidence interval, 1.094-8.362; p =0.020). Moreover, perioperative evaluation of the inferior vena cava showed that patients with postoperative POH had preoperative congestive heart failure and had hypovolemia lower postoperative diameter of the inferior vena cava than patients without POH. CONCLUSIONS Postoperative POH is a potential complication of ASD surgery. The most pertinent risk factor is having an ND. According to our study, patients who have surgery for ASD may experience alterations in their hemodynamics.
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Affiliation(s)
- Morito Takano
- Department of Orthopaedic Surgery, Spine Center, Kitasato Institute Hospital, Tokyo, Japan
| | - Tsuyoshi Iida
- Department of Orthopaedic Surgery, Spine Center, Kitasato Institute Hospital, Tokyo, Japan
| | - Tomohiro Hikata
- Department of Orthopaedic Surgery, Spine Center, Kitasato Institute Hospital, Tokyo, Japan
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17
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Torres RD, Rashed H, Mathur P, Castillo C, Abell T, Terson de Paleville DGL. Autogenic biofeedback training improves autonomic responses in a participant with cervical motor complete spinal cord injury- case report. Spinal Cord Ser Cases 2023; 9:31. [PMID: 37438337 PMCID: PMC10338546 DOI: 10.1038/s41394-023-00593-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/27/2023] [Accepted: 07/04/2023] [Indexed: 07/14/2023] Open
Abstract
STUDY DESIGN Single-subject case design OBJECTIVE: To evaluate the Autogenic Feedback Training Exercise (AFTE) on autonomic nervous system responses. INTRODUCTION AFTE combines specific autogenic exercises with biofeedback of multiple physiological responses. Originally developed by the National Aeronautics and Space Administration (NASA), AFTE is used to improve post-flight orthostatic intolerance and motion sickness in astronauts. Individuals with cervical or upper thoracic spinal cord injury (SCI) often present symptoms of autonomic dysfunction similar to astronauts. We hypothesize that AFTE challenges nervous system baroreflex, gastric and vascular responses often impaired after SCI. METHODS Using a modified AFTE protocol, we trained a hypotensive female participant with cervical motor complete (C5/6-AIS A) SCI, and a male non-injured control participant (NI) and measured blood pressure (BP), heart rate (HR), gastric electrical activity, and microvascular blood volume before, during and after AFTE. The participants were instructed to complete breathing and imagery exercises to help facilitate relaxation. Subsequently, they were instructed to use stressful imagery and breathing exercises during arousal trials. RESULTS Both participants completed 8 sessions of approximately 45 min each. Microvascular blood volume decreased 23% (SCI) and 54% (NI) from the beginning to the end of the stimulation cycles. The participant with SCI became progressively more normotensive and improved levels of gastric electrical activity, while the NI participant's changes in HR, gastric electrical activity, and BP were negligible. CONCLUSIONS AFTE may offer a novel non-pharmacologic intervention to minimize symptoms of dysautonomia in people with SCI.
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Affiliation(s)
- Rachel D Torres
- Interdisciplinary Program in Translational Neuroscience, University of Louisville, Louisville, KY, USA
| | - Hani Rashed
- Division of Gastroenterology, Hepatology & Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Prateek Mathur
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY, USA
| | - Camilo Castillo
- Division of Physical Medicine and Rehabilitation, University of Louisville, Louisville, KY, USA
| | - Thomas Abell
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY, USA
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18
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Wecht JM, Weir JP, Katzelnick CG, Dyson-Hudson TA, Bauman WA, Kirshblum SC. Clinical trial of home blood pressure monitoring following midodrine administration in hypotensive individuals with spinal cord injury. J Spinal Cord Med 2023; 46:531-539. [PMID: 36972219 DOI: 10.1080/10790268.2021.1977904] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Individuals with spinal cord injury (SCI) above thoracic level-6 (T6) experience impaired descending cortical control of the autonomic nervous system which predisposes them to blood pressure (BP) instability, including includes hypotension, orthostatic hypotension (OH), and autonomic dysreflexia (AD). However, many individuals do not report symptoms of these BP disorders, and because there are few treatment options that have been proven safe and effective for use in the SCI population, most individuals remain untreated. OBJECTIVE The primary aim of this investigation was to determine the effects of midodrine (10 mg) prescribed TID or BID in the home environment, compared to placebo, on 30-day BP, study withdrawals, and symptom reporting associated with OH and AD in hypotensive individuals with SCI. DESIGN/METHODS Participants were randomly assigned to received midodrine/placebo or placebo/midodrine, with a 2-weeks washout period in between, and both the participants and investigators were blinded to randomization order. Study medication was taken 2 or 3 times/day, depending on their sleep/wake schedule, BP, and any related symptoms were recorded before and 1 h after each dosage and periodically throughout the day. RESULTS Nineteen individuals with SCI were recruited; however, 9 withdrew prior to completion of the full protocol. A total of 1892 BP recordings (75 ± 48 recordings/participant/30-day period) were collected in the 19 participants over the two 30-day monitoring periods. Average 30-day systolic BP was significantly increased with midodrine compared to placebo (114 ± 14 vs. 96 ± 11 mmHg, respectively; P = 0.004), and midodrine significantly reduced the number of hypotensive BP recordings compared to placebo (38.7 ± 41.9 vs. 73.3 ± 40.6, respectively; P = 0.01). However, compared to placebo, midodrine increased fluctuations in BP, did not improve symptoms of OH, but did significantly worsen the intensity of symptoms associated with AD (P = 0.03). CONCLUSION Midodrine (10 mg) administered in the home environment effectively increases BP and reduces the incidence of hypotension; however these beneficial effects come at the expense of worsened BP instability and AD symptom intensity.
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Affiliation(s)
- Jill M Wecht
- James J Peters VA Medical Center, Bronx, NY, USA
- Departments of Medicine, the Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Rehabilitation Medicine and Human Performance at the Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joseph P Weir
- Department of Health, Sport, and Exercise Sciences, University of Kansas, Lawrence, KS, USA
| | - Caitlyn G Katzelnick
- James J Peters VA Medical Center, Bronx, NY, USA
- Kessler Foundation, West Orange, NJ, USA
| | - Trevor A Dyson-Hudson
- Kessler Foundation, West Orange, NJ, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - William A Bauman
- James J Peters VA Medical Center, Bronx, NY, USA
- Departments of Medicine, the Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Rehabilitation Medicine and Human Performance at the Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven C Kirshblum
- Kessler Foundation, West Orange, NJ, USA
- Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, USA
- Kessler Institute for Rehabilitation, West Orange, NJ, USA
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19
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Smith L, Heriseanu R. Recurrent syncope secondary to autonomic dysfunction in spinal cord injury: a case report. Spinal Cord Ser Cases 2023; 9:23. [PMID: 37391395 PMCID: PMC10313789 DOI: 10.1038/s41394-023-00585-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/02/2023] Open
Abstract
High-level spinal cord injuries are often associated with autonomic impairment, which can result in orthostatic hypotension and syncope. Persistent autonomic dysfunction can manifest with disabling symptoms including recurrent syncopal events. We describe a case of autonomic failure resulting in recurrent syncopal events in a tetraplegic 66-year-old man.
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Affiliation(s)
- Leon Smith
- Spinal Injuries Unit, Royal Rehab, 235 Morrison Rd, Putney, 2112, NSW, Australia.
| | - Roxana Heriseanu
- Spinal Injuries Unit, Royal Rehab, 235 Morrison Rd, Putney, 2112, NSW, Australia
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20
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Soriano JE, Hudelle R, Squair JW, Mahe L, Amir S, Gautier M, Puchalt VP, Barraud Q, Phillips AA, Courtine G. Longitudinal interrogation of sympathetic neural circuits and hemodynamics in preclinical models. Nat Protoc 2023; 18:340-373. [PMID: 36418397 DOI: 10.1038/s41596-022-00764-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 05/27/2022] [Indexed: 11/24/2022]
Abstract
Neurological disorders, including spinal cord injury, result in hemodynamic instability due to the disruption of supraspinal projections to the sympathetic circuits located in the spinal cord. We recently developed a preclinical model that allows the identification of the topology and dynamics through which sympathetic circuits modulate hemodynamics, supporting the development of a neuroprosthetic baroreflex that precisely controls blood pressure in rats, monkeys and humans with spinal cord injuries. Here, we describe the continuous monitoring of arterial blood pressure and sympathetic nerve activity over several months in preclinical models of chronic neurological disorders using commercially available telemetry technologies, as well as optogenetic and neuronal tract-tracing procedures specifically adapted to the sympathetic circuitry. Using a blueprint to construct a negative-pressure chamber, the approach enables the reproduction, in rats, of well-controlled and reproducible episodes of hypotension-mimicking orthostatic challenges already used in humans. Blood pressure variations can thus be directly induced and linked to the molecular, functional and anatomical properties of specific neurons in the brainstem, spinal cord and ganglia. Each procedure can be completed in under 2 h, while the construction of the negative-pressure chamber requires up to 1 week. With training, individuals with a basic understanding of cardiovascular physiology, engineering or neuroscience can collect longitudinal recordings of hemodynamics and sympathetic nerve activity over several months.
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Affiliation(s)
- Jan Elaine Soriano
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland.,Department of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Rémi Hudelle
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Jordan W Squair
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland.,Department of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Lois Mahe
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Suje Amir
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Matthieu Gautier
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Victor Perez Puchalt
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Quentin Barraud
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland
| | - Aaron A Phillips
- Department of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
| | - Gregoire Courtine
- Neuro-X Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. .,Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. .,Defitech Center for Interventional Neurotherapies (.NeuroRestore), EPFL/CHUV/UNIL, Lausanne, Switzerland.
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21
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Shackleton C, Hodgkiss D, Samejima S, Miller T, Perez MA, Nightingale TE, Sachdeva R, Krassioukov AV. When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury. J Neurophysiol 2022; 128:1292-1306. [PMID: 36222423 DOI: 10.1152/jn.00367.2022] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/06/2022] [Indexed: 11/22/2022] Open
Abstract
Spinal cord injury (SCI) results in both motor and autonomic impairments, which can negatively affect independence and quality of life and increase morbidity and mortality. Despite emerging evidence supporting the benefits of activity-based training and spinal cord stimulation as two distinct interventions for sensorimotor and autonomic recovery, the combined effects of these modalities are currently uncertain. This scoping review evaluated the effectiveness of paired interventions (exercise + spinal neuromodulation) for improving sensorimotor and autonomic functions in individuals with SCI. Four electronic databases were searched for peer-reviewed manuscripts (Medline, Embase, CINAHL, and EI-compedex Engineering Village) and data were independently extracted by two reviewers using pre-established extraction tables. A total of 15 studies representing 79 participants were included in the review, of which 73% were conducted within the past 5 years. Only two of the studies were randomized controlled studies, while the other 13 studies were case or case-series designs. Compared with activity-based training alone, spinal cord stimulation combined with activity-based training improved walking and voluntary muscle activation, and augmented improvements in lower urinary tract, bowel, resting metabolic rate, peak oxygen consumption, and thermoregulatory function. Spinal neuromodulation in combination with use-dependent therapies may provide greater neurorecovery and induce long-term benefits for both motor and autonomic function beyond the capacity of traditional activity-based therapies. However, evidence for combinational approaches is limited and there is no consensus for outcome measures or optimal protocol parameters, including stimulation settings. Future large-scale randomized trials into paired interventions are warranted to further investigate these preliminary findings.
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Affiliation(s)
- Claire Shackleton
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Daniel Hodgkiss
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Soshi Samejima
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Tiev Miller
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Monica A Perez
- Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Shirley Ryan Ability Laboratory, Chicago, Illinois
- Edward Hines Jr. VA Hospital, Chicago, Illinois
| | - Thomas E Nightingale
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom
- Centre for Trauma Sciences Research, University of Birmingham, Birmingham, United Kingdom
| | - Rahul Sachdeva
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Andrei V Krassioukov
- International Collaboration on Repair Discoveries, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Spinal Cord Program, GF Strong Rehabilitation Centre, University of British Columbia, Vancouver, British Columbia, Canada
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22
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Sahota IS, Lucci VEM, McGrath MS, Ravensbergen HJC(R, Claydon VE. Cardiovascular and cerebrovascular responses to urodynamics testing after spinal cord injury: The influence of autonomic injury. Front Physiol 2022; 13:977772. [PMID: 36187786 PMCID: PMC9525190 DOI: 10.3389/fphys.2022.977772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/10/2022] [Indexed: 12/02/2022] Open
Abstract
Autonomic dysfunction is a prominent concern following spinal cord injury (SCI). In particular, autonomic dysreflexia (AD; paroxysmal hypertension and concurrent bradycardia in response to sensory stimuli below the level of injury) is common in autonomically-complete injuries at or above T6. AD is currently defined as a >20 mmHg increase in systolic arterial pressure (SAP) from baseline, without heart rate (HR) criteria. Urodynamics testing (UDS) is performed routinely after SCI to monitor urological sequelae, often provoking AD. We, therefore, aimed to assess the cardiovascular and cerebrovascular responses to UDS and their association with autonomic injury in individuals with chronic (>1 year) SCI. Following blood draw (plasma norepinephrine [NE]), continuous SAP, HR, and middle cerebral artery blood flow velocity (MCAv) were recorded at baseline (10-minute supine), during standard clinical UDS, and recovery (10-minute supine) (n = 22, age 41.1 ± 2 years, 15 male). Low frequency variability in systolic arterial pressure (LF SAP; a marker of sympathetic modulation of blood pressure) and cerebral resistance were determined. High-level injury (≥T6) with blunted/absent LF SAP (<1.0 mmHg2) and/or low plasma NE (<0.56 nmol•L−1) indicated autonomically-complete injury. Known electrocardiographic markers of atrial (p-wave duration variability) and ventricular arrhythmia (T-peak–T-end variability) were evaluated at baseline and during UDS. Nine participants were determined as autonomically-complete, yet 20 participants had increased SAP >20 mmHg during UDS. Qualitative autonomic assessment did not discriminate autonomic injury. Maximum SAP was higher in autonomically-complete injuries (207.1 ± 2.3 mmHg) than autonomically-incomplete injuries (165.9 ± 5.3 mmHg) during UDS (p < 0.001). HR during UDS was reduced compared to baseline (p = 0.056) and recovery (p = 0.048) only in autonomically-complete lesions. MCAv was not different between groups or phases (all p > 0.05). Cerebrovascular resistance index was increased during UDS in autonomically-complete injuries compared to baseline (p < 0.001) and recovery (p < 0.001) reflecting intact cerebral autoregulation. Risk for both atrial and ventricular arrhythmia increased during UDS compared to baseline (p < 0.05), particularly in autonomically-complete injuries (p < 0.05). UDS is recommended yearly in chronic SCI but is associated with profound AD and an increased risk of arrhythmia, highlighting the need for continued monitoring during UDS. Our data also highlight the need for HR criteria in the definition of AD and the need for quantitative consideration of autonomic function after SCI.
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Affiliation(s)
- Inderjeet S. Sahota
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Vera-Ellen M. Lucci
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Maureen S. McGrath
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - H. J. C. (Rianne) Ravensbergen
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Victoria E. Claydon
- Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
- *Correspondence: Victoria E. Claydon,
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23
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Flett S, Garcia J, Cowley KC. Spinal electrical stimulation to improve sympathetic autonomic functions needed for movement and exercise after spinal cord injury: a scoping clinical review. J Neurophysiol 2022; 128:649-670. [PMID: 35894427 PMCID: PMC9668071 DOI: 10.1152/jn.00205.2022] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/19/2022] [Accepted: 07/24/2022] [Indexed: 11/22/2022] Open
Abstract
Spinal cord injury (SCI) results in sensory, motor, and autonomic dysfunction. Obesity, cardiovascular disease, and metabolic disease are highly prevalent after SCI. Although inadequate voluntary activation of skeletal muscle contributes, it is absent or inadequate activation of thoracic spinal sympathetic neural circuitry and suboptimal activation of homeostatic (cardiovascular and temperature) and metabolic support systems that truly limits exercise capacity, particularly for those with cervical SCI. Thus, when electrical spinal cord stimulation (SCS) studies aimed at improving motor functions began mentioning effects on exercise-related autonomic functions, a potential new area of clinical application appeared. To survey this new area of potential benefit, we performed a systematic scoping review of clinical SCS studies involving these spinally mediated autonomic functions. Nineteen studies were included, 8 used transcutaneous and 11 used epidural SCS. Improvements in blood pressure regulation at rest or in response to orthostatic challenge were investigated most systematically, whereas reports of improved temperature regulation, whole body metabolism, and peak exercise performance were mainly anecdotal. Effective stimulation locations and parameters varied between studies, suggesting multiple stimulation parameters and rostrocaudal spinal locations may influence the same sympathetic function. Brainstem and spinal neural mechanisms providing excitatory drive to sympathetic neurons that activate homeostatic and metabolic tissues that provide support for movement and exercise and their integration with locomotor neural circuitry are discussed. A unifying conceptual framework for the integrated neural control of locomotor and sympathetic function is presented which may inform future research needed to take full advantage of SCS for improving these spinally mediated autonomic functions.
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Affiliation(s)
- Sarah Flett
- Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Juanita Garcia
- Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Kristine C Cowley
- Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
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24
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Thomas AX, Riviello JJ, Davila-Williams D, Thomas SP, Erklauer JC, Bauer DF, Cokley JA. Pharmacologic and Acute Management of Spinal Cord Injury in Adults and Children. Curr Treat Options Neurol 2022; 24:285-304. [PMID: 35702419 PMCID: PMC9184374 DOI: 10.1007/s11940-022-00720-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2022] [Indexed: 11/26/2022]
Abstract
Purpose of Review This review provides guidance for acute spinal cord injury (SCI) management through an analytical assessment of the most recent evidence on therapies available for treating SCI, including newer therapies under investigation. We present an approach to the SCI patient starting at presentation to acute rehabilitation and prognostication, with additional emphasis on the pediatric population when evidence is available. Recent Findings Further studies since the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) demonstrated a potential functional outcome benefit with ultra-early surgical intervention ≤ 8 h post-SCI. Subsequent analysis of the National Acute Spinal Cord Injury Study (NASCIS) II and NASCIS III trials have demonstrated potentially serious complications from intravenous methylprednisolone with limited benefit. Newer therapies actively being studied have demonstrated limited or no benefit in preclinical and clinical trials with insufficient evidence to support use in acute SCI treatment. Summary Care for SCI patients requires a multi-disciplinary team. Immediate evaluation and management are focused on preventing additional injury and restoring perfusion to the affected cord. Rapid assessment and intervention involve focused neurological examination, targeted imaging, and surgical intervention when indicated. There are currently no evidence-based recommendations for pathomechanistically targeted therapies.
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Affiliation(s)
- Ajay X. Thomas
- Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
- Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX USA
| | - James J. Riviello
- Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - Daniel Davila-Williams
- Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - Sruthi P. Thomas
- Division of Pediatric Physical Medicine and Rehabilitation, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX USA
- Division of Pediatric Neurosurgery, Department of Neurosurgery, Baylor College of Medicine, Houston, TX USA
| | - Jennifer C. Erklauer
- Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
| | - David F. Bauer
- Division of Pediatric Neurosurgery, Department of Neurosurgery, Baylor College of Medicine, Houston, TX USA
| | - Jon A. Cokley
- Division of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX USA
- Department of Pharmacy, Baylor College of Medicine, Houston, TX USA
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25
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Fossey MPM, Balthazaar SJT, Squair JW, Williams AM, Poormasjedi-Meibod MS, Nightingale TE, Erskine E, Hayes B, Ahmadian M, Jackson GS, Hunter DV, Currie KD, Tsang TSM, Walter M, Little JP, Ramer MS, Krassioukov AV, West CR. Spinal cord injury impairs cardiac function due to impaired bulbospinal sympathetic control. Nat Commun 2022; 13:1382. [PMID: 35296681 PMCID: PMC8927412 DOI: 10.1038/s41467-022-29066-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 02/20/2022] [Indexed: 02/08/2023] Open
Abstract
Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury. By combining experimental models with prospective clinical studies, the authors show that spinal cord injury causes a rapid reduction in cardiac function that precedes structural changes, and that the loss of descending sympathetic control is the major cause of reduced cardiac function following spinal cord injury.
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Affiliation(s)
- Mary P M Fossey
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Shane J T Balthazaar
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Jordan W Squair
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Alexandra M Williams
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | | | - Tom E Nightingale
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.,Centre for Trauma Sciences Research, University of Birmingham, Edgabaston, Birmingham, UK
| | - Erin Erskine
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Brian Hayes
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Mehdi Ahmadian
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,School of Kinesiology, Faculty of Education, University of British Columbia, Vancouver, BC, Canada
| | - Garett S Jackson
- Faculty of Health and Social Development, University of British Columbia, Kelowna, BC, Canada
| | - Diana V Hunter
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Katharine D Currie
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Teresa S M Tsang
- Division of Cardiology, University of British Columbia, Vancouver General and University of British Columbia Hospital Echocardiography Department, Vancouver, BC, Canada
| | - Matthias Walter
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Urology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jonathan P Little
- School of Health and Exercise Sciences, University of British Columbia, Kelowna, BC, Canada
| | - Matt S Ramer
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Zoology, Faculty of Science, University of British Columbia, Vancouver, BC, Canada
| | - Andrei V Krassioukov
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada. .,Experimental Medicine, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. .,Division of Physical Medicine and Rehabilitation, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. .,GF Strong Rehabilitation Centre, Vancouver Coastal Health, Vancouver, BC, Canada.
| | - Christopher R West
- International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada. .,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
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26
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Orthostatic systemic and cerebral hemodynamics in newly injured patients with spinal cord injury. Auton Neurosci 2022; 240:102973. [DOI: 10.1016/j.autneu.2022.102973] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 02/25/2022] [Accepted: 03/14/2022] [Indexed: 11/23/2022]
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27
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Da Rocha Rodrigues SF, Priego Quesada JI, Batista Rufino LH, Barbosa Filho V, Rossato M. Physiological parameters and the use of compression stockings in individuals with spinal cord injuries: a scoping review. Spinal Cord 2022; 60:115-121. [PMID: 35017670 DOI: 10.1038/s41393-021-00748-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 12/23/2021] [Accepted: 12/31/2021] [Indexed: 11/08/2022]
Abstract
STUDY DESIGN Scoping review. OBJECTIVE To summarize information on the physiological effects of compression stockings (CS) in individuals with spinal cord injuries (SCI) and suggest areas for future research. METHODS We asked, "What are the physiological effects of CS use in individuals with SCI?" Original studies of patients with SCI regardless of sex and age that focused on SCI and CS were included. Five biomedical databases were searched. Studies were selected by three researchers in two stages, starting with an abstract and title screening and continuing with a full text review for application of the inclusion and exclusion criteria. A narrative synthesis was then performed. RESULTS An initial search yielded 283 titles, of which five met the inclusion criteria and were subjected to the full text review. Among them, there were 78 individuals with SCI. The studies found that the use of CS at rest reduced deep vein thrombosis (DVT) and vascular capacitance but increased systolic blood pressure and norepinephrine level., three studies tested the use of CS During exercise; one found that time of the last lap in a standard court test was negatively affected; however, the greatest benefits were observed after exercises, such as reduced blood lactate level, improved autonomic function, and increased blood flow to the upper limbs. CONCLUSION We conclude that future research should examine the physiological effects and relationship of CS with: (a) pharmacological interventions, (b) body position changes, (c) physical fitness level, (d) wheelchair use duration, (e) exercise-induced thermal stress, (f) thermal stress mitigation, and (g) edema reduction.
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Affiliation(s)
| | - Jose Ignácio Priego Quesada
- Research Group in Sports Biomechanics (GIBD), Department of Physical Education and Sports, University of Valencia, Valencia, Spain
| | - Luiz Henrique Batista Rufino
- Human Performance Laboratory of Faculty of Physical Education and Physiotherapy, Federal University of Amazonas, Manaus, Brazil
| | - Valter Barbosa Filho
- Federal Institute of Education, Science and Technology of Ceara, Aracati, Brazil
- Post-graduate Program in Collective Health, Ceara State University, Fortaleza, Brazil
| | - Mateus Rossato
- Human Performance Laboratory of Faculty of Physical Education and Physiotherapy, Federal University of Amazonas, Manaus, Brazil.
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28
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Management of blood pressure disorders in individuals with spinal cord injury. Curr Opin Pharmacol 2021; 62:60-63. [PMID: 34915401 DOI: 10.1016/j.coph.2021.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 10/21/2021] [Indexed: 12/21/2022]
Abstract
Blood pressure regulation is impacted by a spinal cord injury (SCI) due to impaired descending sympathetic vascular control. Common blood pressure problems in the SCI population include persistently low blood pressure with bouts of orthostatic hypotension and autonomic dysreflexia, which are more prevalent in individuals with lesions above the sixth thoracic vertebral level; however, they may occur regardless of the neurological level of injury. Although blood pressure disorders adversely impact daily function and quality of life, most individuals with SCI do not acknowledge this association. Few pharmacological options have been rigorously tested for safety and efficacy to manage blood pressure disorders in the SCI population. Furthermore, clinical management of any one blood pressure disorder may adversely impact others, as such treatment is complicated and not often prioritized.
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29
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Mishra RK, Goyal K, Bindra A, Singh GP, Kumar N, Sokhal N, Soni KD, Kedia S, Barman SD. An investigation to the prolonged requirement (>7 days) of vasopressors in cervical spinal cord injury patients-a retrospective analysis. Spinal Cord Ser Cases 2021; 7:96. [PMID: 34728603 DOI: 10.1038/s41394-021-00459-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 09/18/2021] [Accepted: 10/05/2021] [Indexed: 11/09/2022] Open
Abstract
STUDY DESIGN Retrospective chart review. OBJECTIVES The primary aim was to identify the number of patients requiring vasopressors beyond the first week of cervical spinal cord injury (SCI). Secondary objectives were to note the type, duration and doses of vasopressors and any association between prolonged vasopressors use and outcome. SETTING Neurosurgical intensive care of a tertiary trauma care centre. METHODS After Ethical approval we retrospectively collected the data of patients of isolated cervical SCI admitted to neurosurgical intensive care from January to December 2017. Vasopressor requirement for sepsis or cardiac arrest was excluded. RESULTS Out of 80 patients analysed, 54 (67.5%) received vasopressors. The prolonged requirement of vasopressors was observed in 77.7%. Our preferred agent was dopamine (64.8%). We found out that longer requirement (in days) of high dose of dopamine was associated with higher survival (p = 0.03). CONCLUSION Our results describe a significant portion of cervical SCI patients need ongoing vasopressor to maintain a mean arterial pressure >65 mm of Hg beyond first week. We observed patients who required longer duration of high dose dopamine had a higher chance of survival suggesting some unknown mechanism of high dose of dopamine. This is first such observation, further studies are needed to substantiate.
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Affiliation(s)
- Rajeeb Kumar Mishra
- Department of Neuroanaesthesia and neurocritical care, National Institute of Mental Health and Neurosciences, Bengaluru, 560029, India
| | - Keshav Goyal
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India.
| | - Ashish Bindra
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Gyaninder Pal Singh
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Niraj Kumar
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Navdeep Sokhal
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Kapil Dev Soni
- Department of Critical and Intensive Care, Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Shweta Kedia
- Department of Neurosurgery, Neurosciences centre, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Sagar Dev Barman
- Department of Neuroanaesthesia and critical care, All India Institute of Medical Sciences, New Delhi, 110029, India
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30
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Hoogenes B, Querée M, Miller WC, Mortenson WB, Townson A, Eng JJ. Evidence on definitions, concepts, outcome instruments, and interventions for chronic fatigue in spinal cord injury: a scoping review protocol. JBI Evid Synth 2021; 19:1999-2006. [PMID: 33851945 DOI: 10.11124/jbies-20-00214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE The objective of this review is to review the existing evidence on definitions, concepts, measurement instruments, and interventions for chronic fatigue in spinal cord injury. INTRODUCTION Chronic fatigue in people with spinal cord injury is an under-studied issue that affects between 25% and 56.6% of people with spinal cord injury. There are questions about how it is defined and managed due to its complex, multifactorial nature and relationship with related conditions. No overview of chronic fatigue in spinal cord injury exists and we are in need of a shared definition of chronic fatigue, as well as a comprehensive review of concepts and evidence supporting outcome instruments and interventions. INCLUSION CRITERIA This review will include empirical and non-empirical studies that focus on definitions, concepts, measurement instruments, and interventions for chronic fatigue in spinal cord injury. Studies that focus on peripheral muscle fatigue will only be included if they include chronic fatigue as a secondary outcome. METHODS This review will be done in three phases. Phase I will provide an overview of definitions of chronic fatigue in spinal cord injury and will include a qualitative analysis of concept attributes and characteristics. Phase II will focus on factors related to chronic fatigue and measurement instruments used to measure chronic fatigue, and phase III will focus on interventions. Full texts will be screened by two independent reviewers against inclusion criteria. Results will be presented in tabular form with a narrative summary.
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Affiliation(s)
- Bob Hoogenes
- Rehabilitation Research Program, G.F. Strong Rehabilitation Centre, Vancouver, BC, Canada
- Faculty of Medicine, Amsterdam University Medical Centre-University of Amsterdam, Amsterdam, Netherlands
| | - Matthew Querée
- Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - William C Miller
- Rehabilitation Research Program, G.F. Strong Rehabilitation Centre, Vancouver, BC, Canada
- Department of Occupational Science and Occupational Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- International Collaboration on Repair Discoveries, Vancouver, BC, Canada
| | - W Ben Mortenson
- Rehabilitation Research Program, G.F. Strong Rehabilitation Centre, Vancouver, BC, Canada
- Department of Occupational Science and Occupational Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- International Collaboration on Repair Discoveries, Vancouver, BC, Canada
| | - Andrea Townson
- Rehabilitation Research Program, G.F. Strong Rehabilitation Centre, Vancouver, BC, Canada
- International Collaboration on Repair Discoveries, Vancouver, BC, Canada
- Division of Physical Medicine and Rehabilitation, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Janice J Eng
- Rehabilitation Research Program, G.F. Strong Rehabilitation Centre, Vancouver, BC, Canada
- Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- International Collaboration on Repair Discoveries, Vancouver, BC, Canada
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Hwang BY, Mampre D, Ahmed AK, Suk I, Anderson WS, Manbachi A, Theodore N. Ultrasound in Traumatic Spinal Cord Injury: A Wide-Open Field. Neurosurgery 2021; 89:372-382. [PMID: 34098572 DOI: 10.1093/neuros/nyab177] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/19/2021] [Indexed: 02/02/2023] Open
Abstract
Traumatic spinal cord injury (SCI) is a common and devastating condition. In the absence of effective validated therapies, there is an urgent need for novel methods to achieve injury stabilization, regeneration, and functional restoration in SCI patients. Ultrasound is a versatile platform technology that can provide a foundation for viable diagnostic and therapeutic interventions in SCI. In particular, real-time perfusion and inflammatory biomarker monitoring, focal pharmaceutical delivery, and neuromodulation are capabilities that can be harnessed to advance our knowledge of SCI pathophysiology and to develop novel management and treatment options. Our review suggests that studies that evaluate the benefits and risks of ultrasound in SCI are severely lacking and our understanding of the technology's potential impact remains poorly understood. Although the complex anatomy and physiology of the spine and the spinal cord remain significant challenges, continued technological advances will help the field overcome the current barriers and bring ultrasound to the forefront of SCI research and development.
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Affiliation(s)
- Brian Y Hwang
- Division of Functional Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David Mampre
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - A Karim Ahmed
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ian Suk
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - William S Anderson
- Division of Functional Neurosurgery, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Amir Manbachi
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Nicholas Theodore
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Logan A, Freeman J, Pooler J, Kent B, Gunn H, Billings S, Cork E, Marsden J. Effectiveness of non-pharmacological interventions to treat orthostatic hypotension in elderly people and people with a neurological condition: a systematic review. JBI Evid Synth 2021; 18:2556-2617. [PMID: 32773495 DOI: 10.11124/jbisrir-d-18-00005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE The objective of this review was to summarize the best available evidence regarding the effectiveness of non-pharmacological interventions to treat orthostatic hypotension (OH) in elderly people and people with a neurological condition. INTRODUCTION Orthostatic hypotension is common in elderly people and people with a neurological condition and can interfere with or limit rehabilitation. Non-pharmacological interventions to treat OH could allow for longer and earlier mobilization, which is recommended in national clinical guidelines for rehabilitation in the acute or sub-acute phase following stroke or other neurological conditions. INCLUSION CRITERIA The review considered people aged 50 years and older, and people aged 18 years and elderly people with a neurological condition. Non-pharmacological interventions to treat OH included compression garments, neuromuscular stimulation, physical counter-maneuvers, aerobic or resistance exercises, sleeping with head tilted up, increasing fluid and salt intake, and timing and size of meals. The comparator was usual care, no intervention, pharmacological interventions, or other non-pharmacological interventions. Outcome measures included systolic blood pressure, diastolic blood pressure, heart rate, cerebral blood flow, observed/perceived symptoms, duration of standing or sitting in minutes, tolerance of therapy, functional ability, and adverse events/effects. METHODS Databases for published and unpublished studies available in English up to April 2018 with no lower date limit were searched. Critical appraisal was conducted using standardized instruments from JBI. Data were extracted using standardized tools designed for quantitative studies. Where appropriate, studies were included in a meta-analysis; otherwise, data were presented in a narrative form due to heterogeneity. RESULTS Forty-three studies - a combination of randomized controlled trials (n = 13), quasi-experimental studies (n = 28), a case control study (n = 1), and a case report (n = 1) - with 1069 participants were included. Meta-analyses of three interventions (resistance exercise, electrical stimulation, and lower limb compression bandaging) showed no significant effect of these interventions. Results from individual studies indicated physical maneuvers such as leg crossing, leg muscle pumping/contractions, and bending forward improved orthostatic hypotension. Abdominal compression improved OH. Sleeping with head up in combination with pharmacological treatment was more effective than sleeping with head up alone. Eating smaller, more frequent meals was effective. Drinking 480 mL of water increased blood pressure. CONCLUSIONS The review found mixed results for the effectiveness of non-pharmacological interventions to treat OH in people aged 50 years and older, and people with a neurological condition. There are several non-pharmacological interventions that may be effective in treating OH, but not all have resulted in clinically meaningful changes in outcome. Some may not be suitable for people with moderate to severe disability; therefore, it is important for clinicians to consider the patient's abilities and impairments when considering which non-pharmacological interventions to implement.
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Affiliation(s)
- Angela Logan
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,Stroke and Neurology Therapy Team, Cornwall Partnership Foundation NHS Trust, Camborne Redruth Community Hospital, Cornwall, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
| | - Jennifer Freeman
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
| | - Jillian Pooler
- Faculty of Health, Peninsula Medical and Dentistry Schools, Plymouth, UK
| | - Bridie Kent
- The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence.,School of Nursing and Midwifery, Faculty of Health, Plymouth University, Plymouth, UK
| | - Hilary Gunn
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK
| | - Sarah Billings
- Stroke Rehabilitation Unit, Livewell Southwest, Mount Gould Hospital, Plymouth, UK
| | - Emma Cork
- Stroke Rehabilitation Department, Northern Devon Healthcare Trust, Northern Devon District Hospital, Barnstaple, UK
| | - Jonathan Marsden
- School of Health Professions, Faculty of Health, Peninsula Allied Health Centre, Plymouth University, Plymouth, UK.,The University of Plymouth Centre for Innovations in Health and Social Care: A JBI Centre of Excellence
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Donovan J, Forrest G, Linsenmeyer T, Kirshblum S. Spinal Cord Stimulation After Spinal Cord Injury: Promising Multisystem Effects. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2021. [DOI: 10.1007/s40141-020-00304-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Herrity AN, Aslan SC, Ugiliweneza B, Mohamed AZ, Hubscher CH, Harkema SJ. Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury. Front Syst Neurosci 2021; 14:614691. [PMID: 33469421 PMCID: PMC7813989 DOI: 10.3389/fnsys.2020.614691] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/03/2020] [Indexed: 12/27/2022] Open
Abstract
Spinal cord injury (SCI) results in profound neurologic impairment with widespread deficits in sensorimotor and autonomic systems. Voluntary and autonomic control of bladder function is disrupted resulting in possible detrusor overactivity, low compliance, and uncoordinated bladder and external urethral sphincter contractions impairing storage and/or voiding. Conservative treatments managing neurogenic bladder post-injury, such as oral pharmacotherapy and catheterization, are important components of urological surveillance and clinical care. However, as urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments. Several human and animal studies, including our previously published reports, have documented gains in bladder function due to activity-based recovery strategies, such as locomotor training. Furthermore, epidural stimulation of the spinal cord (scES) combined with intense activity-based recovery training has been shown to produce volitional lower extremity movement, standing, as well as improve the regulation of cardiovascular function. In our center, several participants anecdotally reported improvements in bladder function as a result of training with epidural stimulation configured for motor systems. Thus, in this study, the effects of activity-based recovery training in combination with scES were tested on bladder function, resulting in improvements in overall bladder storage parameters relative to a control cohort (no intervention). However, elevated blood pressure elicited during bladder distention, characteristic of autonomic dysreflexia, was not attenuated with training. We then examined, in a separate, large cross-sectional cohort, the interaction between detrusor pressure and blood pressure at maximum capacity, and found that the functional relationship between urinary bladder distention and blood pressure regulation is disrupted. Regardless of one's bladder emptying method (indwelling suprapubic catheter vs. intermittent catheterization), autonomic instability can play a critical role in the ability to improve bladder storage, with SCI enhancing the vesico-vascular reflex. These results support the role of intersystem stimulation, integrating scES for both bladder and cardiovascular function to further improve bladder storage.
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Affiliation(s)
- April N. Herrity
- Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States
- Department of Neurological Surgery, University of Louisville, Louisville, KY, United States
| | - Sevda C. Aslan
- Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States
- Department of Neurological Surgery, University of Louisville, Louisville, KY, United States
| | - Beatrice Ugiliweneza
- Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States
- Department of Neurological Surgery, University of Louisville, Louisville, KY, United States
| | - Ahmad Z. Mohamed
- Department of Urology, University of Louisville, Louisville, KY, United States
| | - Charles H. Hubscher
- Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States
- Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, United States
| | - Susan J. Harkema
- Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States
- Department of Neurological Surgery, University of Louisville, Louisville, KY, United States
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Nabata KJ, Tse EK, Nightingale TE, Lee AH, Eng JJ, Querée M, Walter M, Krassioukov AV. The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review. Curr Neuropharmacol 2021; 19:402-432. [PMID: 32310048 PMCID: PMC8033968 DOI: 10.2174/1570159x18666200420085712] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/12/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.
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Affiliation(s)
| | | | | | | | | | | | | | - Andrei V. Krassioukov
- Address correspondence to this author at the International Collaboration On Repair Discoveries (ICORD), University of British Columbia (UBC), Vancouver, Canada; E-mail:
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Abstract
PURPOSE OF REVIEW This article reviews the management of orthostatic hypotension with emphasis on neurogenic orthostatic hypotension. RECENT FINDINGS Establishing whether the cause of orthostatic hypotension is a pathologic lesion in sympathetic neurons (ie, neurogenic orthostatic hypotension) or secondary to other medical causes (ie, non-neurogenic orthostatic hypotension) can be achieved by measuring blood pressure and heart rate at the bedside. Whereas fludrocortisone has been extensively used as first-line treatment in the past, it is associated with adverse events including renal and cardiac failure and increased risk of all-cause hospitalization. Distinguishing whether neurogenic orthostatic hypotension is caused by central or peripheral dysfunction has therapeutic implications. Patients with peripheral sympathetic denervation respond better to norepinephrine agonists/precursors such as droxidopa, whereas patients with central autonomic dysfunction respond better to norepinephrine reuptake inhibitors. SUMMARY Management of orthostatic hypotension is aimed at improving quality of life and reducing symptoms rather than at normalizing blood pressure. Nonpharmacologic measures are the key to success. Pharmacologic options include volume expansion with fludrocortisone and sympathetic enhancement with midodrine, droxidopa, and norepinephrine reuptake inhibitors. Neurogenic supine hypertension complicates management of orthostatic hypotension and is primarily ameliorated by avoiding the supine position and sleeping with the head of the bed elevated.
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An arterial insufficiency ulcer in an individual with cervical spinal cord injury and hypotension. Spinal Cord Ser Cases 2020; 6:42. [DOI: 10.1038/s41394-020-0291-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/05/2020] [Accepted: 05/07/2020] [Indexed: 11/08/2022] Open
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Clinical Implications for Cardiovascular Compromise in Patients With Spinal Cord Injury: A Case Study of Autonomic Dysreflexia, Cardiac Pacing Abnormality, and Orthostatic Hypotension in Contemporary Physical Therapy Management. Cardiopulm Phys Ther J 2020. [DOI: 10.1097/cpt.0000000000000164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Wang S, Wecht JM, Legg Ditterline B, Ugiliweneza B, Maher MT, Lombard AT, Aslan SC, Ovechkin AV, Bethke B, Gunter JTH, Harkema SJ. Heart rate and blood pressure response improve the prediction of orthostatic cardiovascular dysregulation in persons with chronic spinal cord injury. Physiol Rep 2020; 8:e14617. [PMID: 33080121 PMCID: PMC7575221 DOI: 10.14814/phy2.14617] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 09/17/2020] [Accepted: 09/25/2020] [Indexed: 12/17/2022] Open
Abstract
Unstable blood pressure after spinal cord injury (SCI) is not routinely examined but rather predicted by level and completeness of injury (i.e., American Spinal Injury Association Impairment Scale AIS classification). Our aim was to investigate hemodynamic response to a sit-up test in a large cohort of individuals with chronic SCI to better understand cardiovascular function in this population. Continuous blood pressure and ECG were recorded from individuals with SCI (n = 159) and non-injured individuals (n = 48). We found orthostatic hypotension occurred within each level and AIS classification (n = 36). Moreover, 45 individuals with chronic SCI experienced a drop in blood pressure that did not meet the criteria for orthostatic hypotension, but was accompanied by dramatic increases in heart rate, reflecting orthostatic intolerance. A cluster analysis of hemodynamic response to a seated position identified eight distinct patterns of interaction between blood pressure and heart rate during orthostatic stress indicating varied autonomic responses. Algorithmic cluster analysis of heart rate and blood pressure is more sensitive to diagnosing orthostatic cardiovascular dysregulation. This indicates blood pressure instability cannot be predicted by level and completeness of SCI, and the consensus statement definition of orthostatic hypotension is insufficient to characterize the variability of blood pressure and heart rate responses during orthostatic stress. Both blood pressure and heart rate responses are needed to characterize autonomic function after SCI.
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Affiliation(s)
- Siqi Wang
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
| | - Jill M. Wecht
- James J Peters VA Medical CenterBronxNYUSA
- Departments of Medicine and Rehabilitation Medicinethe Icahn School of MedicineMount SinaiNew YorkNYUSA
| | - Bonnie Legg Ditterline
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
| | - Beatrice Ugiliweneza
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
| | - Matthew T. Maher
- James J Peters VA Medical CenterBronxNYUSA
- Kessler Institute for RehabilitationWest OrangeNJUSA
| | - Alexander T. Lombard
- James J Peters VA Medical CenterBronxNYUSA
- Kessler Institute for RehabilitationWest OrangeNJUSA
| | - Sevda C. Aslan
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
| | - Alexander V. Ovechkin
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
| | | | | | - Susan J. Harkema
- Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleKYUSA
- Department of Neurological SurgeryUniversity of Louisville School of MedicineLouisvilleKYUSA
- Frazier Rehab InstituteLouisvilleKYUSA
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Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management. Semin Neurol 2020; 40:550-559. [PMID: 32906175 DOI: 10.1055/s-0040-1713885] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Spinal cord injury (SCI) disrupts autonomic circuits and impairs synchronistic functioning of the autonomic nervous system, leading to inadequate cardiovascular regulation. Individuals with SCI, particularly at or above the sixth thoracic vertebral level (T6), often have impaired regulation of sympathetic vasoconstriction of the peripheral vasculature and the splanchnic circulation, and diminished control of heart rate and cardiac output. In addition, impaired descending sympathetic control results in changes in circulating levels of plasma catecholamines, which can have a profound effect on cardiovascular function. Although individuals with lesions below T6 often have normal resting blood pressures, there is evidence of increases in resting heart rate and inadequate cardiovascular response to autonomic provocations such as the head-up tilt and cold face tests. This manuscript reviews the prevalence of cardiovascular disorders given the level, duration and severity of SCI, the clinical presentation, diagnostic workup, short- and long-term consequences, and empirical evidence supporting management strategies to treat cardiovascular dysfunction following a SCI.
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Krassioukov A, Stillman M, Beck LA. A Primary Care Provider's Guide to Autonomic Dysfunction Following Spinal Cord Injury. Top Spinal Cord Inj Rehabil 2020; 26:123-127. [PMID: 32760191 DOI: 10.46292/sci2602-123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Spinal cord injury (SCI) disrupts the crucial "crosstalk" between the spinal autonomic nervous system and supraspinal control centers. Therefore, SCI may result not only in motor paralysis but also in potentially life-threatening impairments of many autonomic functions including, but not limited to, blood pressure regulation. Despite the detrimental consequences of autonomic dysregulation, management and recovery of autonomic functions after SCI is greatly underexplored. Although impaired autonomic function may impact several organ systems, this overview will focus primarily on disruptions of cardiovascular and thermoregulation and will offer suggestions for management of these secondary effects of SCI.
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Affiliation(s)
- Andrei Krassioukov
- ICORD, Blusson Spinal Cord Centre, University of British Columbia, GF Strong Rehabilitation Center, Vancouver, BC, Canada
| | - Michael Stillman
- Departments of Internal Medicine and Rehabilitation Medicine, Sydney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Lisa A Beck
- Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota
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Ong ETE, Yeo LKP, Kaliya-Perumal AK, Oh JYL. Orthostatic Hypotension Following Cervical Spine Surgery: Prevalence and Risk Factors. Global Spine J 2020; 10:578-582. [PMID: 32677558 PMCID: PMC7359682 DOI: 10.1177/2192568219863805] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
STUDY DESIGN Retrospective case series. OBJECTIVES This study aims to determine the prevalence and risk factors for orthostatic hypotension (OH) in patients undergoing cervical spine surgery. METHODS Data was collected from records of 190 consecutive patients who underwent cervical spine procedures at our center over 24 months. Statistical comparison was made between patients who developed postoperative OH and those who did not by analyzing characteristics such as age, gender, premorbid medical comorbidities, functional status, mechanism of spinal cord injury, preoperative neurological function, surgical approach, estimated blood loss, and length of stay. RESULTS Twenty-two of 190 patients (11.6%) developed OH postoperatively. No significant differences in age, gender, medical comorbidities, or premorbid functional status were observed. Based on univariate comparisons, traumatic mechanism of injury (P = .002), poor ASIA (American Spinal Injury Association) grades (A, B, or C) (P < .001), and posterior surgical approach (P = .045) were found to significantly influence occurrence of OH. Among the significant variables, after adjusting for mechanism of injury and surgical approach, only ASIA grade was found to be an independent predictor. Having an ASIA grade of A, B, or C increased the likelihood of developing OH by approximately 5.978 times (P = .003). CONCLUSION Our study highlights that OH is not an uncommon manifestation following cervical spine surgery. Patients with poorer ASIA grades A, B, or C were more likely to have OH when compared with those with ASIA grades D or E (43.5% vs 7.2%). Hence, we suggest that postural blood pressure should be routinely monitored in this group of patients so that early intervention can be initiated.
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Affiliation(s)
| | | | - Arun-Kumar Kaliya-Perumal
- Tan Tock Seng Hospital, Singapore,Melmaruvathur Adhiparasakthi Institute of Medical Sciences and Research, Melmaruvathur, Tamil Nadu, India
| | - Jacob Yoong-Leong Oh
- Tan Tock Seng Hospital, Singapore,Jacob Yoong-Leong Oh, Department of Orthopaedic Surgery, Spine Division, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore.
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Sachdeva R, Krassioukov AV, Bucksot JE, Hays SA. Acute Cardiovascular Responses to Vagus Nerve Stimulation after Experimental Spinal Cord Injury. J Neurotrauma 2020; 37:1149-1155. [PMID: 31973660 DOI: 10.1089/neu.2019.6828] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Pairing vagus nerve stimulation (VNS) with rehabilitation has emerged as a potential strategy to enhance plasticity and improve recovery in a range of neurological disorders. A recent study highlights the therapeutic promise of VNS in promoting motor recovery after spinal cord injury (SCI). We investigated the safety of acute VNS in a rat model of chronic SCI. We measured the cardiovascular response to various VNS paradigms following chronic high-thoracic SCI that is known to deleteriously impact cardiovascular control. Dose-response experiments with continuous VNS revealed an SCI-dependent increase in sensitivity for heart rate (HR) and blood pressure (BP) compared with controls. A clinically relevant intermittent VNS resulted in transient reduction in HR in rats with SCI; however, BP remained unaltered. In all experiments, the effect lasted only while the VNS stimulus train was present, as HR and BP restored to baseline values as soon as VNS ended. No prolonged episodes of persisting hypotension were seen in either group. Further, VNS did not trigger autonomic dysreflexia or exacerbate the severity of autonomic dysreflexia when induced during or after stimulation sessions. Overall, these findings provide initial evidence that intermittent VNS at parameters used for targeted plasticity therapy (30 Hz, 0.8 mA) appears safe and supports further investigation of this potential therapy for use following SCI.
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Affiliation(s)
- Rahul Sachdeva
- International Collaboration on Repair Discoveries (ICORD), Division of Physical Medicine and Rehabilitation, University of British Columbia, Vancouver, British Columbia, Canada.,Department of Medicine, Division of Physical Medicine and Rehabilitation, University of British Columbia, Vancouver, British Columbia, Canada
| | - Andrei V Krassioukov
- International Collaboration on Repair Discoveries (ICORD), Division of Physical Medicine and Rehabilitation, University of British Columbia, Vancouver, British Columbia, Canada.,Department of Medicine, Division of Physical Medicine and Rehabilitation, University of British Columbia, Vancouver, British Columbia, Canada.,G.F. Strong Rehabilitation Center, Vancouver Coastal Health, Vancouver, British Columbia, Canada
| | - Jesse E Bucksot
- Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Richardson, Texas, USA
| | - Seth A Hays
- Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Richardson, Texas, USA.,Texas Biomedical Device Center, The University of Texas at Dallas, Richardson, Texas, USA.,School of Behavioral Brain Sciences, The University of Texas at Dallas, Richardson, Texas, USA
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Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI. Spinal Cord 2020; 58:959-969. [PMID: 32203065 PMCID: PMC7483245 DOI: 10.1038/s41393-020-0448-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 02/19/2020] [Accepted: 02/24/2020] [Indexed: 12/19/2022]
Abstract
Study Design: Clinical trial. Objectives: Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared to placebo, to increase and normalize systolic blood pressure (SBP) between 110–120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function. Setting: United States clinical research laboratory. Methods: Forty-one healthy hypotensive individuals with chronic (≥ 1-year post-injury) SCI participated in this 2-day study. Seated SBP, CBFv, cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. Results: Compared to placebo, midodrine increased SBP (4±13 vs. 18±24 mmHg, respectively; p<0.05); however, responses varied widely with midodrine (−15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared to placebo. Although higher SBP was associated with higher CBFv (p=0.02), global cognitive function was not improved with midodrine. Conclusions: The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggest careful monitoring of patients following administration.
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Influence of cervical spinal cord injury on thermoregulatory and cardiovascular responses in the human body: Literature review. J Clin Neurosci 2019; 69:7-14. [DOI: 10.1016/j.jocn.2019.08.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/04/2019] [Indexed: 11/20/2022]
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Gibbons TD, Zuj KA, Prince CN, Kingston DC, Peterson SD, Hughson RL. Haemodynamic and cerebrovascular effects of intermittent lower-leg compression as countermeasure to orthostatic stress. Exp Physiol 2019; 104:1790-1800. [PMID: 31578774 DOI: 10.1113/ep088077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 09/30/2019] [Indexed: 02/04/2023]
Abstract
NEW FINDINGS What is the central question of this study? Does smartly timed intermittent compression of the lower legs alter cerebral blood velocity and oxygenation during acute orthostatic challenges? What is the main finding and its importance? Intermittent compression timed to the local diastolic phase increased the blood flux through the legs and heart after two different orthostatic stress tests. Cerebral blood velocity improved during the first minute of recovery, and indices of cerebral tissue oxygenation remained elevated for 2 min. These results provide promise for the use of lower-leg active compression as a therapeutic tool for individuals vulnerable to initial orthostatic hypotension and orthostatic stress. ABSTRACT Intermittent compression of the lower legs provides the possibility of improving orthostatic tolerance by actively promoting venous return and improving central haemodynamics. We tested the hypothesis that intermittent compression of 65 mmHg timed to occur only within the local diastolic phase of each cardiac cycle would attenuate the decrease in blood pressure and improve cerebral haemodynamics during the first minute of recovery from two different orthostatic stress tests. Fourteen subjects (seven female) performed four squat-to-stand transitions and four repeats of standing bilateral thigh-cuff occlusion and release (TCR), with intermittent compression of the lower legs applied in half of the trials. Blood flow in the superficial femoral artery, mean arterial pressure, Doppler ultrasound cardiac output, total peripheral resistance, middle cerebral artery blood velocity (MCAv) and cerebral tissue saturation index (TSI%) were monitored. With both orthostatic stress tests, there was a significant compression × time interaction for superficial femoral artery flow (P < 0.001). The hypotensive state was attenuated with intermittent compression despite decreased total peripheral resistance (squat-to-stand, compression × time interaction, P < 0.001; TCR, compression × time interaction, P = 0.002) as a consequence of elevated cardiac output in both tests (P < 0.001). Intermittent compression also increased MCAv (P = 0.001) and TSI% (P < 0.001) during the squat-to-stand transition and during TCR (MCAv and TSI%, compression × time interaction, P < 0.001). Intermittent compression of the lower legs during quiet standing after an active orthostatic challenge augmented local, central and cerebral haemodynamics, providing potential as a therapeutic tool for individuals vulnerable to orthostatic stress.
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Affiliation(s)
- Travis D Gibbons
- Faculty of Applied Health Sciences, University of Waterloo, Waterloo, ON, Canada
| | - Kathryn A Zuj
- Faculty of Applied Health Sciences, University of Waterloo, Waterloo, ON, Canada
| | - Chekema N Prince
- Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, ON, Canada
| | - David C Kingston
- Faculty of Applied Health Sciences, University of Waterloo, Waterloo, ON, Canada
| | - Sean D Peterson
- Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, ON, Canada
| | - Richard L Hughson
- Schlegel-University of Waterloo Research Institute for Aging, Faculty of Applied Health Sciences, Waterloo, ON, Canada
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Moineau B, Brown A, Brisbois L, Zivanovic V, Miyatani M, Kapadia N, Hsieh JTC, Popovic MR. Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury. J Spinal Cord Med 2019; 42:176-185. [PMID: 31573450 PMCID: PMC6781467 DOI: 10.1080/10790268.2019.1638129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Context: Following spinal cord injury (SCI) at the cervical or upper-thoracic level, orthostatic hypotension (OH) is observed in 13-100% of patients. This study aimed to test the feasibility of conducting a randomized controlled trial combining a dynamic tilt-table (Erigo®) and functional electrical stimulation (FES) to mitigate OH symptoms in the subacute phase after SCI. Design: Pilot study. Setting: A tertiary rehabilitation hospital. Participants: Inpatients who had a C4-T6 SCI (AIS A-D) less than 12 weeks before recruitment, and reported symptoms of OH in their medical chart. Interventions: Screening sit-up test to determine eligibility, then 1 assessment session and 3 intervention sessions with Erigo® and FES for eligible participants. Outcome measures: Recruitment rate, duration of assessment and interventions, resources used, blood pressure, and Calgary Presyncope Form (OH symptoms). Results: Amongst the 232 admissions, 148 inpatient charts were reviewed, 11 inpatients met all inclusion criteria, 7 participated in a screening sit-up test, and 2 exhibited OH. Neither of the two participants recruited in the pilot study was able to fully complete the assessment and intervention sessions due to scheduling issues (i.e. limited available time). Conclusion: This pilot study evidenced the non-feasibility of the clinical trial as originally designed, due to the low recruitment rate and the lack of available time for research in participant's weekday schedule. OH in the subacute phase after SCI was less prevalent and less incapacitating than expected. Conventional management and spontaneous resolution of symptoms appeared sufficient to mitigate OH in most patients with subacute SCI.
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Affiliation(s)
- Bastien Moineau
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
| | - Andrea Brown
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
| | - Louise Brisbois
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
| | - Vera Zivanovic
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
| | - Masae Miyatani
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
| | - Naaz Kapadia
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, Ontario, Canada
| | - Jane T. C. Hsieh
- Lawson Health Research Institute, St. Joseph’s Health Care, London
| | - Milos R. Popovic
- KITE, Toronto Rehabilitation Institute – University Health Network, Toronto, Ontario, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- CRANIA, University Health Network, Toronto, Ontario, Canada
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Deng X, Jing D, Liang H, Zheng D, Shao Z. H₂O₂ Damages the Stemness of Rat Bone Marrow-Derived Mesenchymal Stem Cells: Developing a "Stemness Loss" Model. Med Sci Monit 2019; 25:5613-5620. [PMID: 31353362 PMCID: PMC6683726 DOI: 10.12659/msm.914011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background The number of patients with spinal cord injury caused by motor vehicle accidents, violent injuries, and other types of trauma increases year by year, and bone marrow mesenchymal stem cell (BMSC) transplants are being widely investigated to treat this condition. However, the success rate of BMSCs transplants is relatively low due to the presence of oxidative stress in the new microenvironment. Our main goals in the present study were to evaluate the damaging effects of H2O2 on BMSCs and to develop a model of “stemness loss” using rat BMSCs. Material/Methods Bone marrow-derived mesenchymal stem cells were obtained from the bone marrow of young rats reared under sterile conditions. The stem cells were used after 2 passages following phenotypic identification. BMSCs were divided into 4 groups to evaluate the damaging effects of H2O2: A. blank control; B. 100 uM H2O2; C. 200 uM H2O2 and D. 300 uM H2O2. The ability of the BMSCs to differentiate into 3 cell lineages and their colony formation and migration capacities were analyzed by gene expression, colony formation, and scratch assays. Results The cells we obtained complied with international stem cell standards demonstrated by their ability to differentiate into 3 cell lineages. We found that 200–300 uM H2O2 had a significant effect on the biological behavior of BMSCs, including their ability to differentiate into 3 cell lineages, the expression of stemness-related proteins, and their migration and colony formation capacities. Conclusions H2O2 can damage the stemness ability of BMSCs at a concentration of 200–300 uM.
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Affiliation(s)
- Xiangyu Deng
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Doudou Jing
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Hang Liang
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Dong Zheng
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Zengwu Shao
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)
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Exploring the relationship between self-reported urinary tract infections to quality of life and associated conditions: insights from the spinal cord injury Community Survey. Spinal Cord 2019; 57:1040-1047. [PMID: 31289367 DOI: 10.1038/s41393-019-0323-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 06/25/2019] [Accepted: 06/26/2019] [Indexed: 11/08/2022]
Abstract
STUDY DESIGN Descriptive study OBJECTIVES: Urinary tract infections (UTIs) are one of the most frequent types of infections following spinal cord injury (SCI). Here we assess the relationship between frequency of UTIs and activity level/overall quality of life (QOL) measures, determine the frequency of temporally associated conditions associated with UTI and identify factors associated with frequent UTIs. SETTING Canada METHODS: The Spinal Cord Injury Community Survey was developed to assess major dimensions of community living and health outcomes in persons with chronic SCI in Canada. Participants were stratified by self-reported UTI frequency. The relationship between UTI frequency and QOL, health resource utilization, and temporally associated conditions were assessed. Results were analysed with cross tabulations, χ2 tests, and ordinal logistic regression. RESULTS Overall 73.5% of participants experienced at least one self-reported UTI since the time of injury (mean 18.5 years). Overall QOL was worse with increasing frequency of these events. Those with frequent self-reported UTIs had twice as many hospitalizations and doctors' visits and were limited in financial, vocational and leisure situations, physical health and ability to manage self-care as compared with those with no UTIs. Self-reported UTIs were associated with higher incidence of temporally associated conditions including bowel incontinence, constipation, spasticity, and autonomic dysreflexia. Individuals who were younger and female were more likely to have frequent UTIs and those with constipation and autonomic dysreflexia had worse QOL. CONCLUSIONS Higher frequency self-reported UTIs is related to poor QOL of individuals with long-term SCI. These findings will be incorporated into SCI UTI surveillance and management guidelines.
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