Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.

Prognostic value of early magnetic resonance imaging in the morbidity and mortality of traumatic spinal cord injury.

OBJECTIVE: To assess in individuals with traumatic spinal cord injury (TSCI) the relationship between mortality and need for ICU and early magnetic resonance imaging (MRI), analyzing spinal parenchymal alterations, disruption of vertebral ligaments (DVL) and spinal cord compression (SCC). DESIGN: Retrospective study. SETTING: Third-level hospital, Spinal Cord Injury Unit and ICU. PATIENTS: Individuals with acute TSCI between 2010 and 2019. INTERVENTION: Analysis of MRI performed in the first 72 h. VARIABLES OF INTEREST: Admission to ICU and mortality. RESULTS: 269 cases collected. The pattern that demonstrated higher mortality was cord hemorrhage (16.7%) for 12.5% ​​of single-level edema and 6.5% of multilevel edema (p = 0.125). The same happened with ICU admissions: 69.0% in hemorrhage, 60.2% in multilevel edema and 46.3% in short edema (p = 0.018). Analyzing CCM, mortality was 13.4% with 59.2% of ICU admissions, for 2.2% and 42.2% of individuals without cord compression (p = 0.020 and p = 0.003). The figures of death and ICU admission among cord injuries with DVL were 15.0% and 67.3%, for 6.2% and 44.4% of the individuals without DLV (p < 0.001 and p = 0.013). CONCLUSIONS: The presence of spinal cord hemorrhage, SCC and DVL was associated with a higher admission in ICU. A significant increase in mortality was observed in cases with SCC and DVL.

Evaluation of the prognostic value of extra-parenchymal changes in traumatic spinal cord injury, assessed by magnetic resonance imaging.

OBJECTIVES: To analyze the relationship between neurological progression following traumatic spinal cord injury and Spinal Cord Compression (SCC) and Spinal Ligamentous Injury (LI) by magnetic resonance imaging. DESIGN: Retrospective observational study. SETTING: Spinal Cord Injury Unit (A Coruña, Spain). PARTICIPANTS: Patients were admitted for traumatic spinal cord injury between January 2010 and December 2018 with a magnetic resonance imaging examination performed during the acute phase. INTERVENTION: Evaluation of SCC and LI by magnetic resonance imaging. OUTCOME MEASURES: Comparisons between neurological examination at admission and discharge were made, assessing ASIA Impairment Scale (AIS) grade and motor score. RESULTS: Data from 296 patients were collected. A relationship between SCC and LI and complete injuries were found (P < 0.001). Improvement of the AIS grade was observed in 31.6% of patients with SCC and 31.3% with LI versus 42.7% and 37.8% of subjects without these complications, respectively. Regarding motor score, patients with SCC had lower mean values at the beginning (46.9 ± 26.8 versus 61.1 ± 29.9 in the control group, P < 0.001), as well as less improvement when assessed by the percentage of change (35.1 ± 37.5% versus 49.4 ± 38.1% in the control group, P = 0.010). Similar results were obtained in cases with LI: mean motor score at admission was 45.9 ± 26.7 versus 54.9 ± 29.4 in the control group (P = 0.014) and the percentage of change was 28.5 ± 37.1% in comparison to 46.0 ± 37.5% (P = 0.001) in the controls. CONCLUSIONS: There is a relationship between SCC and LI and complete spinal cord injury. This patient population has lower possibilities of improving their AIS grade and motor score.

Neurological recovery after traumatic spinal cord injury: prognostic value of magnetic resonance.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: Assess the relationship between Magnetic Resonance (MR) image patterns and neurological recovery in patients with Traumatic Spinal Cord Injury (TSCI). SETTING: Spinal cord injury unit in Spain. METHODS: Patients admitted for acute TSCI between January 2010 and December 2018 with a MR exam performed in the acute phase were selected. Five patterns were established: normal, single-level edema, multilevel edema, hemorrhage, and spinal cord transection. Comparisons between the ASIA Injury Severity (AIS) score and Motor Index (MI) at admission and at discharge were made. RESULTS: Collected 296 patients. Normal and cord transection patterns were excluded due to the low number of cases. Single-level edema pattern was primarily observed in cases with incomplete injuries, hemorrhage pattern in complete injuries, and multilevel edema pattern at similar percentages in complete and incomplete lesions. Improvement of the AIS score was found in 40.9% of single-level edema, 20.2% of multilevel edema, and 19.0% of hemorrhage (p = 0.042) patterns. By excluding the AIS grade D from the analyses, the figures increased to 70.3%, 52.2%, and 19.4% respectively (p < 0.001). This significant relationship was confirmed by multivariate analysis, although it was not as relevant as the examination according to ASIA-ISCoS performed at admission (p = 0.005 vs p < 0.001). Mean variation of the MI was also significantly different (p < 0.001) between the three groups: 22.6 ± 21.4 for single-level edema, 16.9 ± 21.1 for multilevel edema, and 4.5 ± 8.4 for hemorrhage. CONCLUSION: MR injury patterns observed at the acute phase are associated with the possibility of improvement of the AIS score and MI.

Características clínicas y pronóstico de la lesión medular traumática en pacientes mayores de 75 años / Clinical characteristics and prognosis of spinal cord injury in individuals over 75 years old

Objetivos Analizar la incidencia y las características de la lesión medular (LM) traumática en la población geriátrica de Galicia (España), el manejo hospitalario y el pronóstico vital y funcional. Material y métodos Estudio comparativo retrospectivo. Se incluyen los pacientes ingresados por LM traumática aguda entre enero de 2010 y diciembre de 2016. Se establecen 2 grupos: mayores y menores de 75 años, actuando los últimos como grupo control. Resultados Recogidos 379 pacientes (27,2% ≥75 años). La etiología más frecuente en el grupo ≥75 años fueron las caídas: 80,6%. El 65,7% presentaban lesiones medulares incompletas con un índice motor (IM) medio de 44,9/100. Al alta el 90,8% eran dependientes, precisando silla de ruedas el 53,8%. La mortalidad hospitalaria fue del 34,9%. En comparación con el grupo control, los pacientes mayores sufrieron más lesiones cervicales (74,8 vs. 51,2%; p<0,001), mayor retraso diagnóstico (31,1 vs. 9,2%; p<0,001) y mortalidad hospitalaria (34,9 vs. 3,2%; p<0,001). Se realizaron menos intervenciones quirúrgicas y con mayor demora. Los porcentajes de ingreso en la UCI, ventilación mecánica y realización de traqueostomía fueron similares. No se encontraron diferencias significativas en cuanto a evolución neurológica según la escala American Spinal Injury Association (ASIA) (p=0,46) o el IM (p=0,48). Conclusiones 1) La frecuencia de LM traumática en ancianos en Galicia es elevada; 2) La evolución neurológica medida por el ASIA es similar a pacientes más jóvenes, si bien el nivel de dependencia al alta es mayor; 3) El nivel de cuidados hospitalarios es similar en ambos grupos salvo por la indicación quirúrgica, y 4) La mortalidad hospitalaria es alta (AU)

Objective To analyze the incidence and characteristics of traumatic spinal cord injury (SCI) in geriatric population of Galicia (Spain), hospital management and functional prognosis. Methods Comparative retrospective study. Patients admitted with acute traumatic SCI during the time period between January 2010 and December 2016 were included. Two groups established: The elderly over and under 75 years of age, with the latter acting as a control group. Results Three hundred seventy-nine patients were studied (27.2% ≥75 years). The main etiology in the >75 years group were falls: 80.6%. There were 65.7% who presented incomplete spinal cord injuries with mean motor index (MI) of 44.9/100. Upon discharge, 90.8% were dependent. Hospital mortality was 34.9%. Those >75 years suffered from more cervical injuries (74.8 vs. 51.2%; p<0.001), longer delay in diagnosis (31.1 vs. 9.2%; p<0.001) and higher hospital mortality (34.9 vs. 3.2%; p<0.001). Fewer surgical interventions were performed, with a longer delay. Percentages for admission into ICU, mechanical ventilation and performing a tracheostomy proved to be similar. There were no significant differences found in the evolution according to the ASIA scale or the MI. Conclusions 1) The frequency of traumatic SCI in the elderly in Galicia is high; 2) Neurological evolution is similar to younger patients but the level of dependence is higher; 3) The level of care provided is similar in both groups, except for the surgical indication, and 4) Hospital mortality is high (AU)

Clinical characteristics and prognosis of spinal cord injury in individuals over 75 years old.

OBJECTIVE: To analyze the incidence and characteristics of traumatic spinal cord injury (SCI) in geriatric population of Galicia (Spain), hospital management and functional prognosis METHODS: Comparative retrospective study. Patients admitted with acute traumatic SCI during the time period between January 2010 and December 2016 were included. Two groups established: The elderly over and under 75 years of age, with the latter acting as a control group. RESULTS: 379 patients were studied (27.2% ≥75 years). The main etiology in the >75 years group were falls: 80.6%. There were 65.7% who presented incomplete spinal cord injuries with mean motor index (MI) of 44.9/100. Upon discharge, 90.8% were dependent. Hospital mortality was 34.9%. Those >75 years suffered from more cervical injuries (74.8 vs. 51.2%, p < 0.001), longer delay in diagnosis (31.1% vs. 9.2%, p < 0.001) and higher hospital mortality (34.9% vs. 3.2%, p < 0.001). Fewer surgical interventions were performed, with a longer delay. Percentages for admission into ICU, mechanical ventilation and performing a tracheostomy proved to be similar. There were no significant differences found in the evolution according to the ASIA scale or the MI. CONCLUSIONS: 1) The frequency of traumatic SCI in the elderly in Galicia is high. 2) Neurological evolution is similar to younger patients but the level of dependence is higher. 3) The level of care provided is similar in both groups, except for the surgical indication. 4) Hospital mortality is high.

Characteristics and Survival of Patients with Acute Traumatic Spinal Cord Injury Above T6 with Prolonged Intensive Care Unit Stays.

OBJECTIVE: To characterize patients with acute traumatic spinal cord injury (ATSCI) above T6 who were admitted to the intensive care unit (ICU) for ≥30 days and their 1-year mortality compared with patients admitted for <30 days. METHODS: A retrospective observational study was performed on 211 patients with an acute traumatic spinal cord injury above T6 who were admitted to an ICU between 1998 and 2017. Multivariate logistic regression analysis was performed to determine the relationship between an ICU stay ≥30 days and mortality after ICU discharge. RESULTS: Of patients, 29.4% were admitted to the ICU for ≥30 days, accounting for 53.4% of total days of ICU stays generated by all patients. An ICU stay ≥30 days was not identified as an independent risk factor for mortality (1-year survival: 88.5% vs. 88.1%; adjusted hazard ratio [HR] 0.80, P = 0.699). Variables identified as predictors of 1-year post-ICU discharge mortality were severity at admission according to the Acute Physiology and Chronic Health Evaluation II score (HR 1.18) and the American Spinal Injury Association Impairment Scale motor score (HR 0.97). Among patients who required invasive mechanical ventilation, a longer duration of the respiratory support was associated with increased mortality (HR 1.01). CONCLUSIONS: Three out of 10 patients with acute traumatic spinal cord injury above T6 require prolonged stays in the ICU. Variables found to be associated with 1-year post-ICU discharge mortality in these patients were American Spinal Injury Association Impairment Scale motor score, severity, and greater duration of invasive mechanical ventilation, but not an ICU stay ≥30 days.

Lesión medular como complicación de la vertebroplastia y la cifoplastia / Spinal cord injury as a complication of vertebroplasty and kyphoplasty

La vertebroplastia y la cifoplastia son técnicas percutáneas mínimamente invasivas que se hallan indicadas en el tratamiento del dolor asociado con fracturas vertebrales osteoporóticas y tumorales. Aunque han demostrado ser técnicas seguras, pueden dar lugar a complicaciones derivadas de la llamada 'fuga de cemento'. Presentamos el caso clínico de dos mujeres con 37 y 62 años, quienes presentaron fracturas toracolumbares múltiples, la primera de etiología traumática y la segunda osteoporótica, con afectación de muro posterior. Tras implementarse dichas técnicas las pacientes presentaron lesión medular incompleta por escape de cemento al canal medular; en el segundo caso se produjo también embolismo pulmonar por cemento. A fin de solucionar dichas complicaciones, se realizaron sendas laminectomías con extracción del material y las pacientes ingresaron a tratamiento rehabilitador; en la paciente con embolismo se inició procedimiento de anticoagulación. Al alta, ambas presentaban mejoría exploratoria y realizaban marcha con ortesis. Se concluye que la vertebroplastia y la cifoplastia son técnicas relativamente seguras aunque no exentas de complicaciones, pues la fuga de cemento a los plexos venosos constituye una complicación conocida y reportada. Es importante una apropiada selección de pacientes, comprobando la integridad del muro posterior; así mismo, los pacientes deben ser evaluados cuidadosamente desde el punto de vista respiratorio.

Vertebroplasty and kyphoplasty are minimally invasive percutaneous techniques indicated for the treatment of pain associated with osteoporotic and tumor vertebral fractures. Although they have proven to be safe techniques, they can give rise to complications derived from the so-called 'cement leakage'. We present the clinical case of two women aged 37 and 62 years, who presented multiple thoracolumbar fractures, the first of traumatic etiology and the second osteoporotic, with posterior wall involvement. After implementing these techniques, the patients presented incomplete medullary lesion due to cement leakage into the medullary canal; in the second case there was also pulmonary embolism due to cement. In order to solve these complications, two laminectomies were performed with removal of the material and the patients were admitted for rehabilitation treatment; in the patient with embolism, anticoagulation procedure was started. At discharge, both patients showed exploratory improvement and were walking with orthosis. We conclude that vertebroplasty and kyphoplasty are relatively safe techniques, although they are not free of complications, since cement leakage to the venous plexus is a known and reported complication. Appropriate patient selection is important, checking the integrity of the posterior wall; likewise, patients should be carefully evaluated from the respiratory point of view.

Clinical characteristics and prognosis of spinal cord injury in individuals over 75 years old. / Características clínicas y pronóstico de la lesión medular traumática en pacientes mayores de 75 años.

OBJECTIVE: To analyze the incidence and characteristics of traumatic spinal cord injury (SCI) in geriatric population of Galicia (Spain), hospital management and functional prognosis. METHODS: Comparative retrospective study. Patients admitted with acute traumatic SCI during the time period between January 2010 and December 2016 were included. Two groups established: The elderly over and under 75 years of age, with the latter acting as a control group. RESULTS: Three hundred seventy-nine patients were studied (27.2% ≥75 years). The main etiology in the >75 years group were falls: 80.6%. There were 65.7% who presented incomplete spinal cord injuries with mean motor index (MI) of 44.9/100. Upon discharge, 90.8% were dependent. Hospital mortality was 34.9%. Those >75 years suffered from more cervical injuries (74.8 vs. 51.2%; p<0.001), longer delay in diagnosis (31.1 vs. 9.2%; p<0.001) and higher hospital mortality (34.9 vs. 3.2%; p<0.001). Fewer surgical interventions were performed, with a longer delay. Percentages for admission into ICU, mechanical ventilation and performing a tracheostomy proved to be similar. There were no significant differences found in the evolution according to the ASIA scale or the MI. CONCLUSIONS: 1) The frequency of traumatic SCI in the elderly in Galicia is high; 2) Neurological evolution is similar to younger patients but the level of dependence is higher; 3) The level of care provided is similar in both groups, except for the surgical indication, and 4) Hospital mortality is high.

A validity study of the Spanish-World Health Organization Quality of Life short version instrument in persons with traumatic spinal cord injury.

STUDY DESIGN: This was a psychometric study. OBJECTIVES: To determine the validity of the Spanish version of the World Health Organization Quality of Life instrument (WHOQOL-BREF) for its use in persons with traumatic spinal cord injury and, as secondary objectives, to correlate the results with variables such as functional status, psychological well-being, and social support. SETTING: Spinal Cord Injury Unit, Complejo Hospitalario Universitario de A Coruña, Galicia (Spain). METHODS: Fifty-four people with spinal cord injury were enrolled in this study. Relevant variables were analyzed based on the scores reported by each participant in the Spanish versions of the WHOQOL-BREF questionnaire, the Spinal Cord Independence Measure, the Hospital Anxiety and Depression Scale (HADS), and the Duke-UNC Functional and Social Support Questionnaire. Both parametric and non-parametric tests were used to compare various variables. The instrument's internal consistency and test-retest reliability were also confirmed. RESULTS: The mean scores of each domain of the WHOQOL-BREF were lower, but nonsignificant, among people who need help to perform activities of daily living. The correlation between the scores obtained in the "Psychological" domain and the items of the HADS scale was significant. Significant differences were also observed when comparing the results of the "Social relationships" and "Environment" domains among people with low scores in the Duke questionnaire. Both an adequate consistency (Cronbach's α: 0.887) and test-retest reliability were demonstrated. CONCLUSION: The Spanish version of the WHOQOL-BREF questionnaire is useful and reliable to evaluate the quality of life of persons with spinal cord injuries in our population of Spanish-speaking people.

Refractory orthostatic hypotension in a patient with a spinal cord injury: Treatment with droxidopa.

CONTEXT: Orthostatic hypotension (OH) is a common complication in patients with a spinal cord injury, mainly affecting complete injuries above neurological level T6. It is generally more severe during the acute phase but can remain symptomatic for several years. FINDINGS: A 65-year-old male with a grade ASIA A post-traumatic cervical spinal cord injury, at neurological level C4, presenting with symptomatic refractory OH. Increased blood pressure (BP) levels and an overall clinical improvement was observed after administering an increasing dose of droxidopa. Treatment was started at a dose of 100 mg twice daily (bid), one to be taken upon rising in the morning and another one in the afternoon, at least three hours before bedtime. According to the patient's symptomatic response, each individual dose was increased by 100 mg at 48-hour intervals. Both increased mean BP levels and a subjective symptomatic improvement were evidenced at a dose of 300 mg bid. CLINICAL RELEVANCE: Treatment with droxidopa increases BP levels and improves symptoms related to refractory OH using all physical and pharmacological measures available. It could therefore constitute an effective alternative treatment for OH in patients with a spinal cord injury.

Risks factors of mechanical ventilation in acute traumatic cervical spinal cord injured patients.

STUDY DESIGN: Descriptive retrospective study. OBJECTIVES: To analyze risk factors associated with mechanical ventilation (MV) in cases of acute traumatic Cervical Spinal Cord Injury (tCSCI). SETTING: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). METHODS: The study included patients with tCSCI who were hospitalized between January 2010 and December 2014. The following variables were analyzed: age, gender, etiology, neurological level, ASIA (American Spinal Injury Association) grade, associated injuries, injury severity score (ISS), ASIA motor score (AMS) at admission and mortality. RESULTS: A total of 146 patients met the study's inclusion criteria. The majority were men (74.7%) with mean age of 62.6 (s.d. ± 18.8) years. Sixty patients (41.1%) required MV. Mean age of ventilated vs. non-ventilated patients was 57.3 vs. 65.7. Men were more likely to require MV than women, ASIA grades A and B were also more likely to need MV than grades C and D, as well as patients with associated injuries. The AMS of patients receiving MV was lower than that of those who did not require MV (20.1 vs. 54.3). Moreover, the ISS was higher in patients receiving MV (31.2 vs. 13.4). An AMS ≤ 37 and an ISS ≥ 13 increased the risk of requiring MV by a factor of 11.98 and 7.28, respectively. CONCLUSIONS: Isolated factors associated with a greater risk of MV in tCSCI were: age, gender, ASIA grade, ISS and AMS. However, the only factor with a significant discriminatory ability to determine the need for MV was the AMS at admission.