Why are cripples paralyzed?

Paraplegics walk independently with electrical stimulation

Three paraplegic patients can run independently again with individually adapted spinal cord stimulation - one kilometer on a treadmill and with aids in everyday situations. According to the authors, there was a training effect even without active stimulation: the patients could apparently move their legs willingly on crutches even without electrical impulses. More than four years ago, they had suffered a spinal cord injury that severely restricted or even completely paralyzed their ability to walk.

Almost six weeks ago, a case report about a paraplegic caused a stir, who was able to take a few steps after intensive training during spinal cord stimulation (SMC, Research in Context of September 24, 2018 [a]). The current work from Lausanne describes three patients who, after intensive training with optimized stimulation, can move their legs willingly without this stimulation. The Swiss scientists have adapted the so-called epidural electrical stimulation of the spinal cord to the patient in such a way that the electrical impulses coincide spatially and temporally with the intended movements. In their view, this very method could be the reason for the neurological recovery of the patients. In addition, the scientists developed a mobile version of the spinal cord stimulation via tablet and voice control that enabled patients to go for a walk or ride a recumbent bike outside of the laboratory.

The researchers have published their results in several articles in journals published by Nature. This research in context focuses primarily on the publication in "Nature" (see primary source). At the same time, another article and a scientific commentary were published in "Nature Neuroscience" (see other research sources).

Overview

  • PD Dr. Rainer Abel, chief physician at the Clinic for Orthopedics and Paraplegics, Bayreuth Clinic
  • Prof. Dr. Norbert Weidner, Medical Director of the Clinic for Paraplegiology, Heidelberg University Hospital
  • Prof. Dr. Winfried Mayr, Professor at the Center for Medical Physics and Biomedical Technology, Medical University of Vienna

Statements

PD Dr. Rainer Abel

Head physician at the Clinic for Orthopedics and Paraplegics, Bayreuth Clinic

“First of all: The work is very exciting. It proves that it is possible to address intact neural networks below the injury in the spinal cord and make them available to the body for voluntary movements. According to the results available, this is possible during a training phase with epidural electrical stimulation, and then also without this stimulation. This is also the most important difference to the previously known research results (for example [1]). There the improvements in motor skills could only be demonstrated under stimulation. "

“These results are not only important because many patients still have residual functions of the spinal cord, which up to now can hardly be exploited by the usual rehabilitation procedures to such an extent that the patient can stand and walk again. The work is also important because the results could make a decisive contribution to the success of neuroregenerative therapies. We know that even with promising approaches, for example the administration of Anti-Nogo A (Antibody used to disinhibit the growth of nerve fibers blocked after paraplegia; Note d. Red.) there is always only an incomplete recovery. Both treatment strategies could complement each other. "

“So far, attempts have been made with the help of electrical stimulation - for example by stimulating individual roots - to trigger individual movements by stimulating the nerves leading to the muscle. In the work presented, on the other hand, targeted stimulation in the area of ​​the posterior roots (Part of the nerves made up of the skin, musculoskeletal system, and viscera that enter the spinal cord; Note d. Red.) in the corresponding section, an 'improved receptivity' for the remaining neuronal activities was established. A muscle contraction is initially not triggered. This means that it is sufficient to activate an otherwise largely meaningless residual function in order to enable walking and standing. After some training, this can even be done without electrical stimulation. Movements do not take place 'involuntarily' during stimulation, but only when the patient wants to make a movement at the same time. "

“The research results are so interesting that they should be tested on a larger number of patients. The method is not yet suitable for everyday use; but it can become that with an acceptable risk if it proves itself. "

"In principle, all patients with central paralysis should benefit from this method, that is, patients with damage to the first motor neuron usually above the medullary conus (End of the spinal cord at the level of the lumbar vertebrae; Note d. Red.). Patients with damage to the cauda equina (Collection of nerve roots below the end of the spinal cord. Red.) will probably benefit little, since stimulus conduction to the muscle is no longer possible here. "

“The gain in function that ultimately occurs even without stimulation can best be explained by the reactivation of functional centers that cannot be achieved with the usual rehabilitation methods. It remains to be seen to what extent the treatment leads to permanent functional gains. However, there is no compelling reason why the functions should be lost again. Presumably a certain 'maintenance therapy' is required. "

"It would certainly be important to test the possibilities of this treatment for the therapy of spasticity."

“The treatment does not make paraplegia curable. The structural losses persist - but it is perhaps suitable for significantly alleviating the consequences and restoring important partial functions to the patient. "

Prof. Dr. Norbert Weidner

Medical Director of the Clinic for Paraplegiology, Heidelberg University Hospital

“I look at the study from the perspective of the clinically active specialist for paraplegics. Comparable to the recently published studies by Gill [1] and Angeli [2], patients with chronic paraplegia recover neurologically, that is, motor recovery - the voluntary control of the muscles of the lower extremities - is achieved through a combination of electrical stimulation and intensive Function-oriented rehabilitation measures are promoted. A patient who is incompletely motor paralyzed at the beginning of the combined therapy shows a much more pronounced motor recovery and, as a result, an improvement in walking function than in a patient in whom no voluntary motor function in the lower extremities is called up at the beginning of the therapy could be. The extensive studies and preliminary work of the working group suggest that the temporally and spatially coordinated electrical stimulation - in contrast to the stimulation that is not coordinated in terms of time and space - of the sensitive posterior roots in the aforementioned studies can produce a higher quality movement sequence while walking. To what extent these results are actually reflected in an improved, everyday-relevant walking function in a larger group of patients, future studies will have to find out. "

“Compared to the studies by Gill [1] and Angeli [2], in which a permanent electrical stimulus is given to the sensitive posterior roots, Wagner's study specifically stimulates certain posterior roots in a limited time window corresponding to defined sections of the gait cycle. "

“As can be seen in the very detailed study by Wagner et al., Incompletely paraplegic patients in particular benefit. In these patients, at least a significant proportion of nerve tracts have been preserved that link the brain with the muscles and, conversely, relay sensitive feedback from the legs to the brain. In the case of completely paraplegics - with only very little preserved nerve tracts beyond the injury to the spinal cord - it cannot be assumed that even 'targeted stimulation' can restore walking function that is relevant to everyday life. "

“It is very likely that the targeted electrical stimulation of the spinal cord is primarily used to wake up the inactive spinal cord below an injury. If the person concerned is actually able to use the regained functions frequently - that is, to walk frequently - then the natural sensitive input while walking is probably sufficient to keep the spinal cord in an active state, which in turn does not require any further electrical stimulation. Future studies must show what extent of walking function can actually be regained and how the regained walking function can be maintained in the longer term. "

Prof. Dr. Winfried Mayr

Professor at the Center for Medical Physics and Biomedical Technology, Medical University of Vienna

“Basically, it is very important to underline that both the recently published work by Gill et al. [1] and the current Courtine group make very interesting contributions to research on movement rehabilitation after paraplegia, but the results are still far from being transferable to clinical routine. One must not give those affected the unjustified hope that there would be a solution that could be used by everyone and that would get them back on their feet. "

“Both studies are methodologically very similar and, on closer inspection, their results are comparable, even if in the current publication by Wagner et al. a direct comparison is presented, which should prove the advantages of the own method. However, each of the stimulation methods would have to be individually optimally adjusted to the paralysis profile of the patient in order to be able to make a really meaningful comparison. "

“As far as can be seen, both studies use the same electrode arrays and stimuli to selectively activate nerve fibers in the ends of the peripheral nerves that open into the spinal cord - called posterior roots or postural roots. The difference is that the American group works with continuous sequences of stimuli of a certain intensity and frequency, while the group in Lausanne uses such pulse sequences over limited time intervals and synchronizes them with movement sequences. Both can lead to similarly beneficial results and the use of both patterns, also in combination, will make sense for further efforts. "

“What is new about this method is the attempt to not only stimulate afferent nerve fibers - fibers that conduct sensory information into the central nervous system - before they enter the spinal cord, but also to synchronize this stimulation with movement sequences and the signal processing in the interneuron networks to provide timely support in the spinal cord. The authors refer to this stimulation method, which has been optimized in terms of space and time, as 'targeted stimulation'. The 'targets' are afferent nerve fibers that can specifically support flexion or extension functions via interneuron networks if there is still a residual influence from centers above the injury site in the spinal cord or brain, which in itself is not sufficient for effective control . Such effects are known from earlier work by various groups. Forms of paralysis of this type are referred to as 'incomplete' and lie between 'incomplete' paralysis with residual functions that can be influenced at will and 'complete' when no movement functions can be activated via neural control. "

“The study presented is an interesting contribution to international research, but it is still very far from a therapy suitable for everyday use. An important step in the right direction is the realization that there will never be a universal solution for all people with paraplegia, only personalized approaches will lead to improvements. Every transverse injury leads to very individual changes in movement control. The best possible therapies can only be planned and carried out through a detailed analysis of the new physiological framework conditions and their changes that develop spontaneously or with the aid of therapy over time. This is taken into account in the study presented, but is also generally an ever increasing trend in research on movement rehabilitation. "

“Therapeutic developments that can ultimately lead to permanent regeneration of movement functions have been observed again and again in the past. In principle, regeneration can take place via the body's own mechanisms alone or as a result of or promoted by a wide variety of therapeutic measures. Whether this is individually possible depends on the severity of the injury and the changed physiological framework. By far not all patients can count on regaining the described movement functions, even with the greatest technical and therapeutic effort. "

“The complete 'cure' of paraplegia will be reserved for a few cases of regenerative accident consequences for a long time to come. Gradual improvements in the therapeutic options will continue to exist and it would be worthwhile to make them available in clinical application - more than is currently the case. This applies above all to the area of ​​spasticity, which interestingly remains completely unmentioned in the present publication, but plays an important role both in the quality of life after paraplegia and in all efforts to rehabilitate movement. "

"The future of movement rehabilitation will lie in personalized multimodal approaches that make the best possible use of available technical, biological and pharmacological tools."

Information on possible conflicts of interest

Prof. Dr. Norbert Weidner: “I would like to start by saying that I am somewhat biased as our clinic is involved in planning a follow-up study (with Courtine and Bloch) in people with spinal cord injury. I try to answer your questions without bias. "

All: None specified.

Primary source

Wagner FB et al. (2018): Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. DOI: 10.1038 / s41586-018-0649-2.

References cited by the experts

[1] Gill ML et al. (2018): Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nature Medicine. DOI: /10.1038/s41591-018-0175-7.

[2] Angeli CA et al. (2018): Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med; 379: 1244-1250. DOI: 10.1056 / NEJMoa1803588.

Further sources of research

[a] Science Media Center Germany (2018): Paraplegic walks with spinal cord stimulation. Research in Context. Status: 09/24/2018.

Formento E et al. (2018): Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nature Neuroscience. DOI: 10.1038 / s41593-018-0262-6.

Moritz C (2018): A giant step for spinal cord injury research. Nature Neuroscience. DOI: 10.1038 / s41593-018-0264-4.