RESUMEN
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.
Asunto(s)
Trastornos del Sueño-Vigilia , Traumatismos de la Médula Espinal , Humanos , Calidad de Vida , Relevancia Clínica , Traumatismos de la Médula Espinal/complicaciones , Hemodinámica/fisiología , Sueño , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
PURPOSE OF REVIEW: Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC. RECENT FINDINGS: Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis. SUMMARY: RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.
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Infarto del Miocardio , Traumatismos de la Médula Espinal , Accidente Cerebrovascular , Adulto , Humanos , HipoxiaRESUMEN
OBJECTIVE: To report on the development and calibration of the new Blood Pressure Dysregulation Measurement System (BPD-MS) item banks that assess the effect of BPD on health-related quality of life (HRQOL) and the daily activities of Veterans and non-Veterans with spinal cord injury (SCI). DESIGN: Cross-sectional survey study. SETTING: Two Veteran Affairs medical centers and a SCI model system site. PARTICIPANTS: 454 respondents with SCI (n=262 American Veterans and n=192 non-Veterans; N=454). INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: The BPD-MS item banks. RESULTS: BPD item pools were developed and refined using literature reviews, qualitative data from focus groups, and cognitive debriefing of persons with SCI and professional caregivers. The item banks then underwent expert review, reading level assessment, and translatability review prior to field testing. The items pools consisted of 180 unique questions (items). Exploratory and confirmatory factor analyses, item response theory modeling, and differential item function investigations resulted in item banks that included a total of 150 items: 75 describing the effect of autonomic dysreflexia on HRQOL, 55 describing the effect of low blood pressure (LBP) on HRQOL, and 20 describing the effect of LBP on daily activities. In addition, 10-item short forms were constructed based on item response theory-derived item information values and the clinical relevance of item content. CONCLUSIONS: The new BPD-MS item banks and corresponding 10-item short forms were developed using established rigorous measurement development standards, which represents the first BPD-specific patient-reported outcomes measurement system unique for use in the SCI population.
Asunto(s)
Traumatismos de la Médula Espinal , Veteranos , Humanos , Presión Sanguínea , Calidad de Vida , Estudios Transversales , Encuestas y Cuestionarios , PsicometríaRESUMEN
Increased pulse wave velocity (PWV), a marker of cardiovascular disease (CVD), has been reported in otherwise healthy individuals with spinal cord injury (SCI) compared with age-matched uninjured controls. Due to decentralized descending sympathetic vascular control, individuals with injuries above T6 are prone to orthostatic hypotension and, as a result, depend on the renin-angiotensin-aldosterone system (RAAS) to maintain orthostatic blood pressure (BP). The purpose of this study was to determine resting PWV, a noninvasive surrogate of central arterial stiffness, in individuals with cervical (C4-T1; n = 11) and thoracic (T6-T12; n = 11) SCI, compared with age-matched controls (controls; n = 11). Next, our aim was to describe group differences in BP, plasma norepinephrine (NE), and renin response to head-up tilt (HUT). Finally, we sought to determine the relationship between PWV and the orthostatic change in BP, NE, and the plasma renin during HUT among the groups. PWV was significantly increased in both cervical (8.81 ± 1.91 m/s) and thoracic (7.36 ± 1.58 m/s) SCI compared with the controls (5.53 ± 0.95 m/s; P < 0.05). The change from supine to 60° HUT in BP and NE was significantly reduced and change in plasma renin was significantly increased in the cervical group compared with the thoracic and control groups. Group affiliation and change in plasma renin were significant predictors of PWV (R2 = 0.63, P = 0.001). These data suggest that dependency on the RAAS for orthostatic BP maintenance may be associated with increased PWV and risk of CVD in the SCI population.NEW & NOTEWORTHY Our novel findings suggest that increased arterial stiffness in individuals with SCI may be due to greater dependency on the RAAS to maintain hemodynamic stability during an orthostatic challenge. Asymptomatic orthostatic hypotension can occur in persons with SCI during transition from the supine to the seated position and during other upright activities of daily living; however, it is seldom addressed by clinicians.
Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico , Análisis de la Onda del Pulso , Sistema Renina-Angiotensina , Traumatismos de la Médula Espinal/complicaciones , Rigidez Vascular , Adaptación Fisiológica , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/etiología , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Posicionamiento del Paciente , Postura , Valor Predictivo de las Pruebas , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/fisiopatología , Pruebas de Mesa InclinadaRESUMEN
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.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Presión Sanguínea , Enfermedades Cardiovasculares , Frecuencia Cardíaca , Sistema Nervioso Parasimpático , Traumatismos de la Médula Espinal , Sistema Nervioso Simpático , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/terapia , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/terapia , Frecuencia Cardíaca/fisiología , Humanos , Sistema Nervioso Parasimpático/fisiopatología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/terapia , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Our objective was to determine differences in brain activation during a processing-speed task in individuals with SCI compared to a group of age-matched healthy controls and to a group of older healthy controls. Ten individuals with cervical SCI (C3-C5), 10 age-matched healthy controls and 10 older healthy controls participated in a cross-sectional study in which performance on neuropsychological tests of processing speed and brain activation were the main outcome measures. The brain areas used by the individuals with SCI during the processing-speed task differed significantly from the age-matched healthy controls, but were similar to the older control cohort, and included activation in frontal, parietal and hippocampal areas. This suggests that individuals with SCI may compensate for processing-speed deficits by relying on brain regions that classically support control cognitive processes such as executive control and memory.
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Cognición , Traumatismos de la Médula Espinal , Estudios Transversales , Humanos , Pruebas Neuropsicológicas , Proyectos PilotoRESUMEN
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 with placebo, to increase and normalize systolic blood pressure (SBP) between 110 and 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, and cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. RESULTS: Compared with 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 with 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 suggests careful monitoring of patients following administration. CLINICAL TRIALS REGISTRATION: NCT02307565.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Cognición/efectos de los fármacos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Midodrina/farmacología , Traumatismos de la Médula Espinal/complicaciones , Vasoconstrictores/farmacología , Adulto , Enfermedad Crónica , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Midodrina/administración & dosificación , Evaluación de Resultado en la Atención de Salud , Vasoconstrictores/administración & dosificaciónRESUMEN
This "Perspectives" article puts forward the notion that measuring heart rate variability, or other forms of cardiac autonomic regulation, after spinal cord injury must be performed during a test of autonomic stress. Resting values of heart rate variability are often similar to those obtained from able-bodied individuals, which may therefore be falsely interpreted as normal or healthy autonomic regulation. However, evidence shows that despite normal resting values, cardiac autonomic control is impaired when individual with spinal cord injury are subjected to a cold face test, head-up tilt, or recovery from exercise. Accordingly, examination of cardiac autonomic function must be performed during an autonomic challenge, as resting measures do not accurately reflect the state of cardiovascular regulation after spinal cord injury and can provide false information.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Electrocardiografía , Prueba de Esfuerzo , Frecuencia Cardíaca , Corazón/inervación , Examen Neurológico , Traumatismos de la Médula Espinal/diagnóstico , Pruebas de Mesa Inclinada , Barorreflejo , Humanos , Posicionamiento del Paciente , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
Assessment of heart rate variability (HRV) is a common approach to examine cardiac autonomic nervous system modulation that has been employed in a variety of settings. Frequently, both the root mean square of successive differences (RMSSD) and SD1, which is a Poincaré plot component, have been used to quantify short-term heart rate variability. It is not typically appreciated, however, that RMSSD and SD1 are identical metrics of HRV. As a reminder to clinicians and researchers who use and study HRV, we show both empirically and mathematically that RMSSD and SD1 are identical metrics. Because the homology between RMSSD and SD1 is not commonly known, the inclusion of both measures has been reported in many recent publications. The inappropriate use of such redundant data may affect the interpretation of HRV studies. Muscle Nerve 56: 674-678, 2017.
Asunto(s)
Electrocardiografía/métodos , Electrocardiografía/estadística & datos numéricos , Frecuencia Cardíaca/fisiología , Modelos Teóricos , Electrocardiografía/normas , HumanosRESUMEN
PURPOSE: Abnormal blood pressure (BP) response to orthostatic maneuvers may predict adverse health outcomes. Orthostatic hypotension (OH) is defined as a fall in BP of ≥20/10 mmHg, and orthostatic hypertension (OHTN) is defined as an increase in systolic BP (SBP) of ≥20 mmHg, with standing. Herein, we document the prevalence of OH and OHTN in American veterans. METHODS: The influence of demographic characteristics, life habits, co-incident medical conditions, and prescription medication use on these prevalence rates and associations between abnormal orthostatic BP responses and severity of self-reported symptoms of fatigue, dizziness, trouble concentrating, and head and neck discomfort were determined. RESULTS: 286 veterans participated; 14 % were classified with OH, 22 % with OHTN, and 64 % with normal BP responses to standing (reference group). An increased prevalence of the diagnosis of diabetes mellitus (27 %) and hypertension (63 %) was noted, which did not differ by orthostatic BP classification. Veterans with OH were older than the reference group and were prescribed more antihypertensive medications than the reference and OHTN groups. While the prevalence of OH increased with age, the prevalence of OHTN was comparable in young (20-30 years) and old (70+ years) veterans (17 vs. 19 %, respectively). The severity of fatigue and dizziness was increased in veterans with OH and OHTN compared to the reference group. CONCLUSION: These data suggest a relatively high prevalence of OH and OHTN, which is associated with increased self-reported severity of fatigue and dizziness in American veterans, findings which may adversely impact long-term health outcomes.
Asunto(s)
Hipertensión/epidemiología , Hipotensión Ortostática/epidemiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos , Veteranos/estadística & datos numéricosRESUMEN
INTRODUCTION: Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP). OBJECTIVES: The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). METHODS: Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded. RESULTS: Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. CONCLUSIONS: These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.
Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Bromuro de Piridostigmina/uso terapéutico , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Presión Sanguínea/efectos de los fármacos , Inhibidores de la Colinesterasa/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Intolerancia Ortostática/tratamiento farmacológico , Intolerancia Ortostática/etiología , Bromuro de Piridostigmina/efectos adversos , Cuadriplejía/fisiopatología , Posición Supina , Pruebas de Mesa Inclinada , Adulto JovenRESUMEN
OBJECTIVE: Increased prevalence of heart rate and blood pressure abnormalities are evident in persons with spinal cord injury (SCI), but age, comorbid medical conditions, and prescription medication use may contribute. To determine differences in the prevalence of cardiac acceleration (heart rate ≥80 beats per minute), hypotension (blood pressure ≤110/70mmHg), orthostatic hypotension (OH) (-20/-10mmHg with upright positioning), and hypertension (HTN) (blood pressure ≥140/90mmHg) in veterans with and without SCI. DESIGN: Observational trial. SETTING: Medical center. PARTICIPANTS: Subjects included veterans with SCI (n=62; cervical: tetraplegia, C3-8; high thoracic, T1-5; low thoracic, T7-L2) and veterans without SCI (n=160). INTERVENTIONS: None. MAIN OUTCOME MEASURES: We assessed medical history, prescription medication use, and heart rate and blood pressure during a routine clinical visit. Prevalence rates of cardiac acceleration, hypotension, OH, and HTN were calculated using binary logistic regression analysis with 95% confidence intervals. The influence of SCI status, age, smoking status, cardiovascular diagnoses, and use of prescribed antihypertensive medications on the prevalence of abnormal heart rate and blood pressure recordings was determined. RESULTS: The diagnosis of HTN was reduced in the high thoracic and tetraplegia groups compared with the non-SCI and low thoracic groups. Use of antihypertensive medications was increased in the low thoracic group compared with the other 3 groups and was increased in the non-SCI group compared with the tetraplegia group. The prevalence of cardiac acceleration was reduced, and the prevalence of systolic hypotension was increased in the tetraplegia group. The prevalence of diastolic hypotension was increased in all SCI groups compared with the non-SCI group. For all analyses, increased prevalence of abnormal heart rate and blood pressure recordings was not further explained by the covariates, with the exception of age, cardiovascular diagnoses, and antihypertensive medications in the cardiac acceleration model; however, SCI status remained significant and was the dominant predictor variable. CONCLUSIONS: Our data suggest that SCI status contributes to the prevalence of cardiac acceleration and systolic and diastolic hypotension regardless of cardiovascular medical conditions or prescription antihypertensive medication use.
Asunto(s)
Frecuencia Cardíaca/fisiología , Hipertensión/epidemiología , Hipotensión/epidemiología , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/fisiopatología , Veteranos , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuadriplejía/epidemiología , Cuadriplejía/fisiopatología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Traumatic spinal cord injury (SCI) is associated with significant psychological and physical challenges. A multidisciplinary approach to management is essential to ensure recovery during the acute phase, and comprehensive rehabilitative strategies are necessary to foster independence and quality of life throughout the chronic phase of injury. Complications that beset these individuals are often a unique consequence of SCI, and knowledge of the effects of SCI upon organ systems is essential for appropriate management. According to the National SCI Statistical Center (NSCISC), as of 2010 there were an estimated 265,000 persons living with SCI in the United States, with approximately 12,000 incidence cases annually. Although life expectancy for newly injured individuals with SCI is markedly reduced, persons with chronic SCI are expected to live about as long as individuals without SCI; however, longevity varies inversely with level of injury. Since 2005, 56 % of persons with SCI are tetraplegic, and due to paralysis of respiratory muscles, these individuals may be especially prone to pulmonary complications, which remain a major cause of mortality among persons with chronic SCI. We at the VA Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI at the James J. Peters VA Medical Center have devoted more than 25 years to the study of secondary medical conditions that complicate SCI. Herein, we review pulmonary research at the Center, both our past and future endeavors, which form an integral part of our multidisciplinary approach toward achieving a greater understanding of and improving care for veterans with SCI.
Asunto(s)
Pulmón/fisiopatología , Cuadriplejía/etiología , Músculos Respiratorios/fisiopatología , Enfermedades Respiratorias/etiología , Traumatismos de la Médula Espinal/complicaciones , Humanos , Puntaje de Gravedad del Traumatismo , Esperanza de Vida , New York , Valor Predictivo de las Pruebas , Pronóstico , Cuadriplejía/diagnóstico , Cuadriplejía/fisiopatología , Cuadriplejía/terapia , Calidad de Vida , Pruebas de Función Respiratoria , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/fisiopatología , Enfermedades Respiratorias/terapia , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Estados Unidos , United States Department of Veterans AffairsRESUMEN
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 81â ±â 51 therapy sessions/participant in the TXT and 60â ±â 27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9â ±â 8 sessions/participant in the TXT group and 10â ±â 12 sessions/participant in the UC group. Neither the total number of therapy sessions (Pâ =â 0.16) nor group assignment (Pâ =â 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.
Asunto(s)
Presión Sanguínea , Hipotensión Ortostática , Traumatismos de la Médula Espinal , Humanos , Hipotensión Ortostática/etiología , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/diagnóstico , Hipotensión Ortostática/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Presión Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Antihipertensivos/uso terapéutico , Pacientes Internos , Factores de Tiempo , AncianoRESUMEN
Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .
Asunto(s)
Brazo , Mano , Cuadriplejía , Traumatismos de la Médula Espinal , Humanos , Cuadriplejía/terapia , Cuadriplejía/fisiopatología , Masculino , Mano/fisiopatología , Femenino , Persona de Mediana Edad , Adulto , Brazo/fisiopatología , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Estimulación de la Médula Espinal/métodos , Resultado del Tratamiento , Calidad de Vida , Estudios Prospectivos , Enfermedad Crónica , Anciano , Terapia por Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/efectos adversosRESUMEN
AIM: To determine the effect of a 12-month intent-to-treat testosterone (T) replacement therapy (TRT) trial on QTa interval variability (QTaVI) in hypogonadal (HG) men with spinal cord injury (SCI). METHOD: A prospective, controlled 12-month TRT trial was completed in 22 healthy, chronic, nonambulatory men with SCI. Based on serum T concentration, subjects were designated as HG (≤ 11.3 nmol/l) or eugonadal (EG ≥ 11.4 nmol/l). Digital 3-lead electrocardiograms were performed. Heart rate (RR), heart rate variability [including total power (TPRR), low frequency (LFRR) and high frequency (HFRR)], QTa, QTe, and RT intervals, QTC (Bazett formula), QTVN, and QTaVI were calculated and evaluated at baseline and at 12 months. Lipoprotein profiles (triglycerides, total cholesterol, low-density and high-density lipoproteins) were obtained at the respective time points. RESULTS: Based on serum T concentration, 13 subjects were designated as HG and 11 as EG. During the trial, there were no group differences for RR, QTa, QTe or RT intervals, QTC, TPRR, HFRR, or lipoproteins. The HG group was older (p < 0.05) and their LFRR was lower (p < 0.05) at baseline. At baseline, QTaVI was significantly greater in the HG group compared to the EG group [-0.17 (0.92) vs. -1.07 (0.90); p < 0.05]. After TRT, this group difference was no longer present [-0.44 (0.87) vs. -0.65 (0.85)] and the change in the HG group was significant (p < 0.05). CONCLUSION: Hypogonadism in men with SCI was associated with elevated QTaVI at baseline. After 12 months of physiological TRT, the QTaVI improved in association with raising T into the normal range. These findings occurred independently of the prolongation of the QT interval.
Asunto(s)
Corazón/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Hipogonadismo/tratamiento farmacológico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Testosterona/uso terapéutico , Adulto , Electrocardiografía , Corazón/fisiología , Humanos , Hipogonadismo/complicaciones , Hipogonadismo/fisiopatología , Masculino , Persona de Mediana Edad , Descanso/fisiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología , Testosterona/farmacología , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. DESIGN: Open-label dose titration trial. SETTING: A Veterans Administration Medical Center. PARTICIPANTS: Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. INTERVENTIONS: Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4. MAIN OUTCOME MEASURES: BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. RESULTS: Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits. CONCLUSIONS: Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI.
Asunto(s)
Droxidopa/uso terapéutico , Hemodinámica/efectos de los fármacos , Hipotensión/tratamiento farmacológico , Hipotensión/etiología , Traumatismos de la Médula Espinal/complicaciones , Adulto , Relación Dosis-Respuesta a Droga , Droxidopa/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , United States Department of Veterans AffairsRESUMEN
OBJECTIVES: To identify medically relevant aspects of blood pressure dysregulation (BPD) related to quality of life in individuals with spinal cord injury (SCI), and to propose an integrated conceptual framework based on input from both individuals with SCI and their clinical providers. This framework will serve as a guide for the development of a patient-reported outcome (PRO) measure specifically related to BPD. DESIGN: Three focus groups with individuals with SCI and 3 groups with SCI providers were analyzed using grounded-theory based qualitative analysis to ascertain how blood pressure impacts health-related quality of life (HRQOL) in individuals with SCI. SETTING: Focus groups were conducted at 2 Veterans Affairs medical centers and a research center. PARTICIPANTS: Individuals with SCI (n=27) in 3 focus groups and clinical providers (n=25) in 3 focus groups. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Qualitative analysis indicated that all focus groups spent the highest percentage of time discussing symptoms of BPD (39%), followed by precipitators/causes of BPD (16%), preventative actions (15%), corrective actions (12%), and the impact that BPD has on social or emotional functioning (8%). While patient/consumer focus groups and provider focus groups raised similar issues, providers spent more time discussing precipitators/causes of BPD and preventative actions (38%) than patient/consumer groups (24%). CONCLUSIONS: These results suggest that BPD uniquely and adversely impacts HRQOL in persons with SCI. While both individuals with SCI and their providers highlighted the relevant symptoms of BPD, the SCI providers offered additional detailed information regarding the precipitators/causes and what can be done to prevent/treat BPD. Further, the results suggest that persons with SCI are aware of how BPD impacts their HRQOL and are able to distinguish between subtle signs and symptoms. These findings exemplify the need for a validated and sensitive clinical measurement tool that can assess the extent to which BPD impacts HRQOL in patients with SCI.
Asunto(s)
Presión Sanguínea/fisiología , Calidad de Vida , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/psicología , Anciano , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , United States Department of Veterans AffairsRESUMEN
Spinal cord injury (SCI) results in motor and sensory impairments that can be identified with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Although, SCI may disrupt autonomic neural transmission, less is understood regarding the clinical impact of decentralized autonomic control. Cardiovascular regulation may be altered following SCI and the degree of impairment may or may not relate to the level of AIS injury classification. In general, persons with lesions above T1 present with bradycardia, hypotension, and orthostatic hypotension; functional changes which may interfere with rehabilitation efforts. Although many individuals with SCI above T1 remain overtly asymptomatic to hypotension, we have documented deficits in memory and attention processing speed in hypotensive individuals with SCI compared to a normotensive SCI cohort. Reduced resting cerebral blood flow (CBF) and diminished CBF responses to cognitive testing relate to test performance in hypotensive non-SCI, and preliminary evidence suggests a similar association in individuals with SCI. Persons with paraplegia below T7 generally present with a normal cardiovascular profile; however, our group and others have documented persistently elevated heart rate and increased arterial stiffness. In the non-SCI literature there is evidence supporting a link between increased arterial stiffness and cognitive deficits. Preliminary evidence suggests increased incidence of cognitive impairment in individuals with paraplegia, which we believe may relate to adverse cardiovascular changes. This report reviews relevant literature and discusses findings related to the possible association between decentralized cardiovascular autonomic control and cognitive dysfunction in persons with SCI.