An article published in Nature Biomedical Engineering discussed a recent study in which researchers from the United States used commercially available electrodes for Closed-Loop Spinal Cord Stimulation (SCS) in three individuals with lower limb amputations. They found that this approach helped elicit somatosensations of the missing foot, leading to improved balance, better gait stability, and a reduction in phantom limb pain in the patients.
Background
Approximately 0.15 million people in the USA undergo lower limb amputation annually, resulting in significant challenges such as mobility issues and phantom limb pain. While treatment options like limb prosthetics and medications exist, individuals with amputations continue to face falls, gait problems, and persistent phantom limb pain. These issues are related to the disruption of somatosensory feedback from the missing limb. Therefore, restoring somatosensations in the amputated limb can alleviate these issues by correcting sensorimotor mismatches and improving functional outcomes.
There is evidence that electrical stimulation of peripheral nerves can help elicit sensations in the missing limb and provide tactile feedback. However, the clinical application of this approach is limited by its surgical complexity and can pose a particular challenge in patients with peripheral neuropathy. SCS is proving to be a promising alternative to peripheral nerve stimulation.
Prior studies have shown that this established technique can be used to alleviate chronic pain and restore sensations in the missing upper limb.
Therefore, the researchers in the present study aimed to utilize SCS to restore sensations in the missing foot in patients who underwent lower limb amputation due to trauma or diabetic peripheral neuropathy.
Study Details
The study included three individuals (aged 21-70 years) who underwent unilateral lower limb amputation approximately 3-7 years prior. The exclusion criteria were pregnancy/lactation, glycosylated hemoglobin >8, presence of metal/medical implants, and the use of anticoagulants.
In the enrolled patients, commercially available SCS electrodes were percutaneously implanted in the thoracolumbar epidural space to stimulate the lateral lumbosacral spinal cord. Stimulation pulses were charge-balanced, biphasic, and consisted of symmetric cathodic and anodic phases. Several testing sessions, each lasting up to 6 hours, were conducted to identify electrode contacts that elicited sensations in the missing foot.
A closed-loop system was developed to modulate SCS based on pressure signals recorded from an insole under the prosthesis. The real-time somatosensory feedback from the system was used to monitor balance, gait, and phantom limb pain in the weeks following the implantation.
The location of the elicited sensations (mechanical, movement, tingling, and temperature) was determined, and the quality of sensations was assessed using various descriptors grouped as naturalistic or parasthetic. The change in amplitude required to help participants identify the more intense stimulus with a 75% probability was defined as the „just noticeable difference“ (JND).
Linear regression was used to determine the potential relationship between stimulation amplitude and perceived magnitude. A sensory organization test (SOT) was used to assess balance, functional gait assessment (FGA) scores were used to quantify gait stability, and the McGill Pain Questionnaire (MPQ) and visual analog scale (VAS) were used to assess phantom limb pain.
Results and Discussion
Beyond the initial two weeks of the study, all three participants were found to have regained sensations in the missing foot (including toe and heel). Sensations in the missing limbs required higher stimulation amplitudes, but they were consistently accompanied by sensations in the residual limbs. Participants experienced a combination of naturalistic and parasthetic descriptors in varying proportions, with no discernible correlation to the frequency or intensity of stimulation.
The stimulus detection thresholds varied between participants, ranging from 0.6 to 4 mA, with the multipolar stimulation exhibiting higher thresholds compared to monopolar stimulation. JNDs were found to be in the range of 0.05 to 0.3 mA. Perceived strength of stimulation increased almost linearly with stimulation amplitude for all participants and electrodes.
Following SCS, participants 2 and 3 achieved higher SOT scores and showed a reduction in falls compared to baseline, indicating improved balance. In the analysis of gait stability, a clinically significant improvement (>4 points) in FGA scores was observed in participant number 3.
Phantom limb pain decreased by 50% compared to baseline in participants 1 and 3, while participant 2 had a decrease of less than one VAS point. The MPQ analysis showed a clinically meaningful decrease in phantom limb pain for participants 1 and 2. However, participant 3 initially experienced a decrease, followed by an increase in pain scores, but there was an overall decrease in the episodes of phantom limb pain over the weeks.
Conclusion
This is the first study to demonstrate the restoration of sensations in patients with amputations related to diabetic peripheral neuropathy. Regardless of the cause of amputation, the results highlight lumbosacral SCS as a promising, clinically feasible intervention for restoring sensations and improving function in lower limb amputees, ultimately enhancing their quality of life. Additional research is needed to confirm these results in a larger group of participants, including sham stimulation, blinding by the examiner, pre-assessment of phantom limb pain, and regular reporting of pain scores.