Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury

Locomotor training on treadmills can improve recovery of stepping in spinal cord injured animals and patients. Likewise, lesioned rats treated with antibodies against the myelin associated neurite growth inhibitory protein, Nogo-A, showed increased regeneration, neuronal reorganization and behavioural improvements. A detailed kinematic analysis showed that the hindlimb kinematic patterns that developed in anti-Nogo-A antibody treated versus treadmill trained spinal cord injured rats were significantly different. The synchronous combined treatment group did not show synergistic effects. This lack of synergistic effects could not be explained by an increase in pain perception, sprouting of calcitonin gene-related peptide (CGRP) positive fibres or by interference of locomotor training with anti-Nogo-A antibody induced regeneration and sprouting of descending fibre tracts. The differential mechanisms leading to behavioural recovery during task-specific training and in regeneration or plasticity enhancing therapies have to be taken into account in designing combinatorial therapies so that their potential positive interactive effects can be fully expresse

Advanced Robotic Therapy Integrated Centers (ARTIC): an international collaboration facilitating the application of rehabilitation technologies

Background: The application of rehabilitation robots has grown during the last decade. While meta-analyses have shown beneficial effects of robotic interventions for some patient groups, the evidence is less in others. We established the Advanced Robotic Therapy Integrated Centers (ARTIC) network with the goal of advancing the science and clinical practice of rehabilitation robotics. The investigators hope to exploit variations in practice to learn about current clinical application and outcomes. The aim of this paper is to introduce the ARTIC network to the clinical and research community, present the initial data set and its characteristics and compare the outcome data collected so far with data from prior studies. Methods: ARTIC is a pragmatic observational study of clinical care. The database includes patients with various neurological and gait deficits who used the driven gait orthosis Lokomat® as part of their treatment. Patient characteristics, diagnosis-specific information, and indicators of impairment severity are collected. Core clinical assessments include the 10-Meter Walk Test and the Goal Attainment Scaling. Data from each Lokomat® training session are automatically collected. Results: At time of analysis, the database contained data collected from 595 patients (cerebral palsy: n = 208; stroke: n = 129; spinal cord injury: n = 93; traumatic brain injury: n = 39; and various other diagnoses: n = 126). At onset, average walking speeds were slow. The training intensity increased from the first to the final therapy session and most patients achieved their goals. Conclusions: The characteristics of the patients matched epidemiological data for the target populations. When patient characteristics differed from epidemiological data, this was mainly due to the selection criteria used to assess eligibility for Lokomat® training. While patients included in randomized controlled interventional trials have to fulfill many inclusion and exclusion criteria, the only selection criteria applying to patients in the ARTIC database are those required for use of the Lokomat®. We suggest that the ARTIC network offers an opportunity to investigate the clinical application and effectiveness of rehabilitation technologies for various diagnoses. Due to the standardization of assessments and the use of a common technology, this network could serve as a basis for researchers interested in specific interventional studies expanding beyond the Lokomat®

Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?

The definitive version is available at http://www.nature.com/nm/journal/v13/n5/pdf/nm1595.pdfProgress continues in developing reparative interventions to enhance recovery after experimental spinal cord injury (SCI). Much of the progress has been made with rodents, but they differ in some important ways from humans and other primates in size, neuroanatomy, neurophysiology, physiology, biochemistry, immunology, and behavior. Questions discussed were to what extent SCI rodent models present limitations for ensuring the efficacy and safety of a treatment for humans, and under what circumstances it would be advantageous or necessary to test treatments in non-human primates before or as an adjunct to clinical trials in human patients. We focus on the recovery of skilled motor control, which enables us to compare and contrast the known differences in the organization of the motor systems and in the behavior among rodents, non-human primates, and humans. In addition, we point out critical issues related to safety in the context of promoting neural connections after an injury that could lead to malfunction. Non-human primates and humans share a myriad of similarities between the structure of their motor systems and motor behavior. Therefore, the non-human primate SCI model provides many unique advantages for testing experimental effects and understanding the safeness of a reparative intervention to promote functional recovery following SCI with the appropriate relevance for humans. We conclude that non-human primate studies are critical for the timely and safe translation of selected potential interventions designed to repair neuromotor impairments in humans.This paper summarizes the discussions that took place in a workshop sponsored and organized by the Christopher Reeve Foundation (CRF).Peer reviewe

Clinical application of robotics and technology in restoration of walking

Second editionRobots for neurorehabilitation have been designed principally to automate repetitive labor-intensive training and to support therapists and patients during different stages of rehabilitation. Devices designed for body weight-supported treadmill training are promising task-oriented tools intended to assist in the restoration of gait. In early rehabilitation, robots provide a safe environment through the use of a suspension harness and assistance in achieving a more physiological gait pattern while promoting a high number of repetitions. In the later stages of rehabilitation, more sophisticated control strategies, virtual environment scenarios, or the possibility to address specific gait deficits by modulating different parameters extends their application. Scientific and clinical evidence for the effectiveness, safety, and tolerability of these devices exists; however documentation of their comparative advantages to conventional therapies is limited. This might be due to the lack of appropriate selection parameters of locomotor training interventions based on functional impairments. Despite this shortcoming, robotic devices are being integrated into clinical settings with promising results. Appropriate use is dependent on the clinicians’ knowledge of different robotic devices as well as the ability to utilize the devices’ technical features, thereby allowing patients to benefit from robot-aided gait training throughout the rehabilitation continuum with the ultimate goal of safe and efficient overground walking. This chapter will provide an overview on the rationales of introducing robots into the clinic and discuss their value in various neurological diagnoses. In addition, recommendations for goal setting and practice of robot-assisted training based on disease- related symptoms and functional impairment are summarized

Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity

Central nervous system (CNS) injuries are particularly traumatic, owing to the limited capabilities of the mammalian CNS for repair. Nevertheless, functional recovery is observed in patients and experimental animals, but the degree of recovery is variable. We review the crucial characteristics of mammalian spinal cord function, tract development, injury and the current experimental therapeutic approaches for repair. Regenerative or compensatory growth of neurites and the formation of new, functional circuits require spontaneous and experimental reactivation of developmental mechanisms, suppression of the growth-inhibitory properties of the adult CNS tissue and specific targeted activation of new connections by rehabilitative training

Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury

Locomotor training on treadmills can improve recovery of stepping in spinal cord injured animals and patients. Likewise, lesioned rats treated with antibodies against the myelin associated neurite growth inhibitory protein, Nogo-A, showed increased regeneration, neuronal reorganization and behavioural improvements. A detailed kinematic analysis showed that the hindlimb kinematic patterns that developed in anti-Nogo-A antibody treated versus treadmill trained spinal cord injured rats were significantly different. The synchronous combined treatment group did not show synergistic effects. This lack of synergistic effects could not be explained by an increase in pain perception, sprouting of calcitonin gene-related peptide (CGRP) positive fibres or by interference of locomotor training with anti-Nogo-A antibody induced regeneration and sprouting of descending fibre tracts. The differential mechanisms leading to behavioural recovery during task-specific training and in regeneration or plasticity enhancing therapies have to be taken into account in designing combinatorial therapies so that their potential positive interactive effects can be fully expressed