Spinal Cord Injury Treatments: an interview with expert Andrei Krassioukov

Dr. Krassioukov, do you think that we currently have treatment options for spinal cord injuries that were previously unavailable?

“It’s a complex question. First, I would argue that the concept of treatment holds different meanings for individuals with spinal cord injuries as well as for clinicians. If you ask someone who has recently sustained an injury, they might say, “I want to walk; I want to cure my paralysis.” For them, a cure primarily means regaining the ability to walk. However, if you speak with someone who has been using a wheelchair for a year or two, their priorities regarding treatment may be entirely different.”.

What would it be?

“We know from numerous studies conducted worldwide that most individuals with chronic spinal cord injuries prioritize bowel and bladder control, as well as sexual function, above all else. For those with high tetraplegia, however, the recovery of hands motor function ranks as their top priority. So, we need to differentiate between a treatment for motor paralysis and one for what I call ‘invisible disabilities’, issues that are not so obvious as paralysis such as blood pressure instability, sexual dysfunctions, urinary bladder and fecal incontinence, and so on”.

But now we have treatment options that were not available in the past, correct? 

“We are still investigating and have gained some initial understanding of the situation. One important consideration is that our present clinical assessment of individuals with spinal cord injury predominately relies on a basic neurological evaluation involving ‘the motor and sensory function assessments’. Lately, we have realized that this approach may be insufficient and requires incorporation of additional assessments including Magnetic Resonance Imaging (MRI) and electrophysiological evaluations. Furthermore, we are increasingly discovering that what we previously classified as ‘complete neurological injury’ in many patients is, in fact, anatomically incomplete (also known as discipline injuries). This indicates that, although these patients may not exhibit any neurological functions below the level of injury, imaging of the spinal cord reveals that a small portion of the white matter remains preserved, albeit not functioning very well. It is silent. This is one of the potential mechanisms that we believe is assisting some people in restoring their function through novel technology”.

Can you mention a few of these mechanisms?

“One mechanism that enhances conduction and connectivity through these silent and partially preserved pathways is spinal cord stimulation. As a result, we may observe some recovery of both motor and autonomic functions. We also believe that the spinal cord below the level of injury undergoes functional and morphological changes. However, by applying certain neuromodulation techniques—such as electrical stimulation or pharmacological interventions—this segment of the spinal cord could be partially revitalized, allowing us to regain functions that would otherwise remain absent without neuromodulation. Furthermore, there is also the possibility that the spinal cord may elicit significant neural regenerative effects that promote recovery. However, we still need to investigate these mechanisms further”.

What research is currently being conducted to understand the mechanisms of spinal cord modulation?

“Numerous laboratories, including my own and Dr. Grégoire Courtine’s laboratory at the École Polytechnique Fédérale de Lausanne, in Switzerland, have begun these assessments. We are using animal models to investigate how neuromodulation operates at the spinal cord level. Although we are still exploring a precise mechanisms of spinal cord stimulation, I can share that we recently published a comprehensive review detailing all potential mechanisms for which we have some evidence, as well as hypothetical mechanisms for the recovery of function through the use of neuromodulation”.

Does electrical stimulation play the most significant role in research and future clinical activities?

“I think so. For many years, we primarily used electrical stimulation on muscles. About 15 to 20 years ago, this approach was considered pioneering and innovative. But what is electrical stimulation of muscles? We directly stimulate the muscles, allowing us to command them to work or contract through an electrical device. With spinal cord stimulation, we can activate voluntary movement. As I previously mentioned, the spinal cord stimulation allowed us to activate partially preserved but silent pathways, triggering voluntary movement and improving abnormal autonomic functions. Furthermore, recent studies have also demonstrated that simultaneous stimulation of the brain and spinal cord, when connected through advanced computer devices, can also lead to intriguing recovery of functions. However, it is important to note that this is still in the early stages of research”.

How important is intention of movement?

“Voluntary control is essential. We are focusing on and have evidence that a person who had no voluntary control of their muscles for years following a spinal cord injury can regain some function if we apply appropriate stimulation to the spinal cord — not the muscles. Suddenly, a person can regain voluntary and intentional control of their hands or lower extremities”.

What are your thoughts on regenerative medicine as a treatment for spinal cord injuries?

“As a scientist, I am truly excited about the experimental models and results observed in vitro and in animal studies. It is remarkable to witness how axons can regenerate after injury. Unfortunately, humans are not as easily studied as cells in a petri dish. We are complex beings and intricate organisms. As you may know, while we have demonstrated some regenerative capacity in the adult spinal cord and central nervous system to restore appropriate connectivity and reestablish the mechanisms that existed prior to injury, so far, we have been unable to reproduce this in humans. It is quite challenging. Over the past 15 to 20 years, we have come to understand that restoring an injured central nervous system involves coordinated actions of multiple cell types, signaling pathways, and tissue components, rather than a single mechanism”.

What other factors are involved?

“First, we need to create an environment conducive to the axonal regeneration pathway. Next, the axon must be precisely directed to locate the appropriate target and establish functional connections. Ideally, if all these steps are successfully completed, the lost functions will be restored. However, after an injury, it is common for the target that was previously connected to the appropriate axon, as well as the relevant centers above the injury, to begin interacting with other neurons, often resulting in the establishment of new, inappropriate connections. This phenomenon is known as maladaptive plasticity or abnormal plasticity. The seemingly inappropriate sprouting, which we have thoroughly documented in my laboratory and others, has become a significant issue, as it disrupts the establishment of proper connections within the spinal cord”.

Do you think that the assessment of the vegetative system plays a role in improving  diagnostic and treatment possibilities? 

“Throughout my 45 years of research in clinical work, I have dedicated myself to understanding the functioning of the autonomic or vegetative nervous system following spinal cord injuries. This area of study is crucial, as every single action in our body involves more than just motor control. For example, the autonomic nervous system plays a crucial role in maintaining our overall physiological balance. It is responsible for regulating several essential functions, including blood pressure, heart rate, and oxygen levels, while also ensuring proper body temperature regulation. That is why it is also crucial to assess the functions of the vegetative or autonomic nervous system following an injury, as recommended by the American Spinal Injury Association and the International Spinal Cord Society”.