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.

Relationship between spatiotemporal parameters and clinical outcomes in children with bilateral spastic cerebral palsy: Clinical interpretation proposal.

BACKGROUND: Understanding the links between gait disorders, impairments, and activity limitations is essential for correctly interpreting the instrumented gait analysis. We aimed to evaluate the relationships between spatiotemporal parameters and clinical outcomes in children with bilateral spastic cerebral palsy, and find out whether spatiotemporal parameters provide clinical information regarding gait pattern and walking. METHODS: Data from 19 children with bilateral spastic cerebral palsy (nine males, ten females, 9.6 ± 2.8 years old) were collected retrospectively. All children underwent an instrumented gait analysis and a standardized clinical assessment. Seven spatiotemporal parameters were calculated: non-dimensional cadence, stride length, step width, gait speed, first double support, single support, and time of toe off. Clinical outcomes included measures of two different components of the International Classification of Functioning, Disability and Health - Children and Youth version: body functions and structures (spasticity, contractures and range of motion, and deformities), and activities and participation (gross motor function, and walking capacity). Pearson correlation, ANOVA, Student's t, Mann-Whitney U, and Kruskal-Wallis tests were used to analyze relationships. Spatiotemporal parameters related to clinical outcomes of body functions and structures were interpreted as outcome measures of gait pattern, while those related to clinical outcomes of activities and participation were interpreted as outcome measures of walking. RESULTS: Non-dimensional cadence, stride length, and gait speed showed relationships (p < 0.05) with hip flexors spasticity and hindfoot deformity, ankle plantar flexors spasticity, and hindfoot deformity, respectively. All spatiotemporal parameters except non-dimensional cadence showed correlation (p < 0.05) with gross motor function and walking capacity. CONCLUSIONS: Spatiotemporal parameters provide clinical information regarding both gait pattern and walking.

Gait parameters in children with bilateral spastic cerebral palsy: a systematic review of randomized controlled trials.

AIM: To identify the gait parameters used to assess gait disorders in children with bilateral spastic cerebral palsy (CP) and evaluate their responsiveness to treatments. METHOD: A systematic search within PubMed, Web of Science, and Scopus (in English, 2000-2016) for randomized controlled trials of children with bilateral spastic CP who were assessed by instrumented gait analysis (IGA) was performed. Data related to participants and study characteristics, risk of bias, and outcome measures were collected. A list of gait parameters responsive to clinical interventions was obtained. RESULTS: Twenty-one articles met the inclusion criteria. Eighty-nine gait parameters were identified, 56 of which showed responsiveness to treatments. Spatiotemporal and kinematic parameters were widely used compared to kinetic and surface electromyography data. The majority of responsive gait parameters were joint angles at the sagittal plane (flexion-extension). INTERPRETATION: The IGA yields responsive outcome measures for the gait assessment of children with bilateral spastic CP. Spatiotemporal and kinematic (at sagittal plane) parameters are the gait parameters used most frequently. Further research is needed to establish the relevant gait parameters for each clinical problem. WHAT THIS PAPER ADDS: Fifty-six responsive gait parameters for children with bilateral spastic cerebral palsy were identified. Most responsive gait parameters belong to joint angles time-series at sagittal plane. Spatiotemporal and kinematic parameters are widely used compared to kinetic and surface electromyography parameters.

PARÁMETROS DE LA MARCHA EN NIÑOS CON PARÁLISIS CEREBRAL ESPÁSTICA BILATERAL: UNA REVISIÓN SISTEMÁTICA DE ENSAYOS CONTROLADOS ALEATORIOS: OBJETIVO: Identificar los parámetros de la marcha utilizados para evaluar los trastornos de la marcha en niños con parálisis cerebral espástica (PC) bilateral y evaluar su capacidad de respuesta a los tratamientos. MÉTODO: Se realizó una búsqueda sistemática en PubMed, Web of Science y Scopus (en inglés, 2000-2016) de ensayos controlados aleatorios de niños con PC espástica bilateral que fueron evaluados mediante análisis de marcha instrumentado (AMI). Se recopilaron datos relacionados con los participantes y las características del estudio, el riesgo de sesgo y las medidas de resultado. Se obtuvo una lista de parámetros de marcha que respondieron a las intervenciones clínicas. RESULTADOS: Veintiún artículos cumplieron con los criterios de inclusión. Se identificaron 89 parámetros de la marcha, 56 de los cuales mostraron capacidad de respuesta a los tratamientos. Los parámetros espaciotemporales y cinemáticos fueron utilizados ampliamente en comparación con los datos de electromiografía de superficie y cinética. La mayoría de los parámetros de marcha que respondieron fueron ángulos articulares en el plano sagital (flexión-extensión). INTERPRETACIÓN: El AMI produce medidas de resultados que responden a la evaluación de la marcha de los niños con PC espástica bilateral. Los parámetros espaciotemporales y cinemáticos son los parámetros de la marcha utilizados con más frecuencia. Se necesita más investigación para establecer los parámetros de marcha relevantes para cada problema clínico.

PARÂMETROS DE MARCHA EM CRIANÇAS COM PARALISIA CEREBRAL BILATERAL ESPÁSTIA: UMA REVISÃO SISTEMÁTICA DE ESTUDOS RANDOMIZADOS CONTROLADOS: OBJETIVO: Identificar os parâmetros de marcha usados para avaliar desordens da marcha em crianças com paralisia cerebral espástica (PC) e avaliar sua responsividade a tratamentos. MÉTODO: Uma busca sistemática na PubMed, Web of Science, e Scopus (Inglês, 2000-2016) por estudos randomizados controlados de crianças com PC bilateral que foram avaliadas com análise de marcha instrumental (AMI) foi realizada. Os dados relacionados a participantes e características dos estudos, risco de vies, e medidas de resultado foram coletadas. Uma lista de parâmetros responsivos a intervenções clínicas foi obtida. RESULTADOS: Vinte e um artigos atenderam aos critérios de inclusão. Oitenta e nove parâmetros de marcha foram identificados, 56 dos quais mostraram responsividade a tratamentos. Parâmetros espaço-temporais e cinemáticos foram amplamente usados em comparação com dados cinéticos e de eletromiografia de superfície. A maioria dos parâmetros responsivos foram ângulos articulares no plano sagittal (flexo-extensão). INTERPRETAÇÃO: A AMI fornece medidas de resultados responsivas para avaliação da marcha em crianças com PC bilateral espástica. Parâmetros espaço-temporais e cinemáticos são os mais frequentemente usados. Mais pesquisas são necessárias para estabelecer os parâmetros relevantes para cada problema clínico.

Gait training in human spinal cord injury using electromechanical systems: effect of device type and patient characteristics.

OBJECTIVE: To report the clinical improvements in spinal cord injury (SCI) patients associated with intensive gait training using electromechanical systems according to patient characteristics. DESIGN: Prospective longitudinal study. SETTING: Inpatient SCI rehabilitation center. PARTICIPANTS: Adults with SCI (n=130). INTERVENTION: Patients received locomotor training with 2 different electromechanical devices, 5 days per week for 8 weeks. MAIN OUTCOME MEASURES: Lower-extremity motor score, Walking Index for Spinal Cord Injury, and 10-meter walking test data were collected at the baseline, midpoint, and end of the program. Patients were stratified according to the American Spinal Injury Association (ASIA) category, time since injury, and injury etiology. A subgroup of traumatic ASIA grade C and D patients were compared with data obtained from the European Multicenter Study about Human Spinal Cord Injury (EM-SCI). RESULTS: One hundred and five patients completed the program. Significant gains in lower-limb motor function and gait were observed for both types of electromechanical device systems, to a similar degree. The greatest rate of improvement was shown in the motor incomplete SCI patients, and for patients <6 months postinjury. The positive response associated with training was not affected by injury etiology, age, sex, or lesion level. The trajectory of improvement was significantly enhanced relative to patients receiving the conventional standard of care without electromechanical systems (EM-SCI). CONCLUSIONS: The use of electromechanical systems for intensive gait training in SCI is associated with a marked improvement in lower-limb motor function and gait across a diverse range of patients and is most evident in motor incomplete patients, and for patients who begin the regimen early in the recovery process.

Preclinical Development of a Therapy for Chronic Traumatic Spinal Cord Injury in Rats Using Human Wharton's Jelly Mesenchymal Stromal Cells: Proof of Concept and Regulatory Compliance.

(1) Background: the use of Mesenchymal Stromal Cells (MSC) in emerging therapies for spinal cord injury (SCI) hold the potential to improve functional recovery. However, the development of cell-based medicines is challenging and preclinical studies addressing quality, safety and efficacy must be conducted prior to clinical testing; (2) Methods: herein we present (i) the characterization of the quality attributes of MSC from the Wharton's jelly (WJ) of the umbilical cord, (ii) safety of intrathecal infusion in a 3-month subchronic toxicity assessment study, and (iii) efficacy in a rat SCI model by controlled impaction (100 kdynes) after single (day 7 post-injury) and repeated dose of 1 × 106 MSC,WJ (days 7 and 14 post-injury) with 70-day monitoring by electrophysiological testing, motor function assessment and histology evaluation; (3) Results: no toxicity associated to MSC,WJ infusion was observed. Regarding efficacy, recovery of locomotion was promoted at early time points. Persistence of MSC,WJ was detected early after administration (day 2 post-injection) but not at days 14 and 63 post-injection. (4) Conclusions: the safety profile and signs of efficacy substantiate the suitability of the presented data for inclusion in the Investigational Medicinal Product Dossier for further consideration by the competent Regulatory Authority to proceed with clinical trials.

Gait event detection using kinematic data in children with bilateral spastic cerebral palsy.

BACKGROUND: Ground reaction forces are the gold standard for detecting gait events, but they are not always applicable in cerebral palsy. Ghoussayni's algorithm is an event detection method based on the sagittal plane velocity of heel and toe markers. We aimed to evaluate whether Ghoussayni's algorithm, using two different thresholds, was a valid event detection method in children with bilateral spastic cerebral palsy. We also aimed to define a new adaptation of Ghoussayni's algorithm for detecting foot strike in cerebral palsy, and study the effect of event detection methods on spatiotemporal parameters. METHODS: Synchronized kinematic and kinetic data were collected retrospectively from 16 children with bilateral spastic cerebral palsy (7 males and 9 females; age 8.9 ± 2.7 years) walking barefoot at self-selected speed. Gait events were detected using methods: 1) ground reaction forces, 2) Ghoussayni's algorithm with a threshold of 0.5 m/s, and 3) Ghoussayni's algorithm with a walking speed dependent threshold. The new adaptation distinguished how foot strikes were performed (heel and/or toe) comparing the timing when the foot markers velocities fell below the threshold. Differences between the three methods, and between spatiotemporal parameters calculated from the two Ghoussayni's thresholds were analyzed. FINDINGS: There were statistically significant (P < 0.05) differences between methods 1 and 3, and between some spatiotemporal parameters calculated from methods 2 and 3. Ghoussayni's algorithm showed better performance for foot strike than for toe off. INTERPRETATION: Ghoussayni's algorithm using 0.5 m/s is valid in children with bilateral spastic cerebral palsy. Event detection methods affect spatiotemporal parameters.

[Spanish consensus document for the diagnosis, treatment and management of neurogenic bladder.] / Documento de consenso español para el diagnóstico, el tratamiento y el manejo de la vejiga neurógena.

OBJECTIVES: The purpose of this document is to establish practical recommendations on neurogenic bladder (NB) management based on scientific evidence and medical and nursing perspective in Spinal Cord Injury (SCI) Units as a first multidisciplinary consensual approach in Spain. METHODS: This paper reports results from the first modified Delphi consensus building exercise on this procedure. A committee of recognised opinion-leaders in rehabilitation and urology with special interest in NB was constituted. A working group formed by rehabilitation doctors, urologists and nursing staff of SCI and Neurorehabilitation Units of a number of Spanish hospitals and specialised centres associated with the panel of NB experts have prepared this document. RESULTS: This review provided an overview of the main aspects described by the different clinical guidelines already available and highlighted the need to focus on recommendations in special priority situations in which there was no consensus. In view of the considerable impact this condition has on quality of life, patients should be offered help to better understand the disorder and they should be taught how to use the treatment techniques to obtain satisfactory results and promote their autonomy. CONCLUSIONS: This article presents a version of guidelines for patients with NB. The guidelines define the clinical profile of patients to provide the best evidence- based care and also an overview of the current drug and surgical treatments of NB.

OBJETIVO: El objetivo de este documento es establecer recomendaciones prácticas sobre el manejo de la vejiga neurógena (VN) en función de la evidencia científica y las perspectivas médicas y de enfermería en Unidades de Lesionados Medulares (ULM) como un primer enfoque de consenso multidisciplinar en España.MÉTODOS: En este artículo se presentan los resultados del primer ejercicio de consenso basado en metodología Delphi modificada sobre este procedimiento. Se constituyó un comité del que formaron parte reconocidos expertos en rehabilitación y urología, especializados en el manejo de VN. Este documento ha sido elaborado por un grupo de trabajo formado por médicos especialistas en rehabilitación, urólogos y personal de enfermería de ULM y unidades de Neurorrehabilitación de varios hospitales y centros especializados españoles asociados con el panel de expertos sobre VN. RESULTADOS: Esta revisión ofrece un resumen de los principales aspectos descritos en diversas guías clínicas ya disponibles y destaca la necesidad de centrarse en recomendaciones sobre situaciones especialmente prioritarias sobre las que actualmente no existe consenso. En vista del considerable impacto de esta enfermedad sobre la calidad de vida, los pacientes deben recibir ayuda para que comprendan mejor su enfermedad y también deben recibir formación sobre el uso de técnicas de tratamiento para conseguir resultados satisfactorios y fomentar su autonomía. CONCLUSIONES: En este artículo se presenta una versión de la guía para el manejo de pacientes con VN. Las guías definen el perfil clínico de los pacientes para ofrecer la mejor asistencia basada en la evidencia y también un resumen de los tratamientos farmacológicos y quirúrgicos actuales para la VN.

Decrease of spasticity with muscle vibration in patients with spinal cord injury.

OBJECTIVE: Spasticity is common after spinal cord injury (SCI). Exaggerated tendon jerks, clonus, and spasms are key features of spasticity that result from hyperexcitability of the stretch reflex circuit. Here we studied the effects of vibration on the rectus femoris muscle (RF) on clinical and electrophysiological measures of spasticity in the leg. METHODS: Nineteen SCI patients with spasticity and nine healthy subjects were studied at baseline and under stimulation (vibration at 50 Hz during 10 min on the thigh). Neurophysiological studies included evaluation of the soleus T wave and Hmax/Mmax ratio. Clinical measurements of spasticity were the score in the Modified Ashworth Scale (MAS), range of motion (ROM), and duration and frequency of clonus. RESULTS: Patients with incomplete SCI (iSCI) presented higher number of cycles and longer duration of clonus than patients with complete SCI (cSCI). The Hmax/Mmax ratio and T wave amplitude at baseline were significantly larger in iSCI patients than in cSCI or healthy subjects. During vibration, we found a significant reduction of MAS and duration of clonus, and an increase in ROM, in all patients as a group. The Hmax/Mmax ratio and the T wave amplitude decreased significantly in both, patients and controls. CONCLUSIONS: Prolonged vibration on proximal lower extremity muscles decreased limb spasticity in patients with spinal cord injury, regardless of whether the lesion is complete or incomplete. SIGNIFICANCE: Muscle vibration may be useful for physical therapy, by facilitating passive and active movements of the extremities in spastic SCI patients.