Abstract

Introduction

This talk will provide an overview of the exciting development of a newly defined surgical technique Targeted Sensory Reinnervation (TSR) which, together with a non-invasive vibrotactile device, is able to effectively treat phantom limb pain or prevent it from occurring. Phantom limb syndrome and neuromas affect a high percentage of amputee patients and massively compromise their quality of life. Their treatment remains a challenge, and in most cases, is limited to symptomatic treatment [1,2]. Even just the so-called phantom limb sensation can be life-limiting for anyone affected and can lead to a dependency on medication.

Mots Clés

Targeted Sensory Reinnervation

Corps du résumé / Matériels et méthodes

It was this feeling of being powerless in the treatment of these symptoms that motivated us 10 years ago to implement a completely new strategy for pain management in a patient with severe drug-dependent phantom limb pain. We wondered how we could close the loop in the sensory cortex caused by the loss or paralysis of a limb. We know that this loop of information is the cause of phantom limb pain and neuropathic pain, as afferent stimuli do not find their way into the central nervous system (CNS). The answer to this was quite simple, we needed to create a situation where the brain receives stimuli from the periphery and the loop is closed [3].

Based on our research in the literature, and our own experience with TMR (Targeted Muscle Reinnervation), we knew that afferent somatosensory nerve fibers reinnervate the dermis beyond a target muscle segment after a TMR procedure [4]. This phenomenon was created by accidental subcutaneous defatting, which led to uncontrolled sprouting of sensory fibers into the skin, triggering native and referred cutaneous sensations [5].

Based on these findings, we then developed a new technique of TSR (Targeted Sensory Reinnervation) in the lower limb (LL), where we take a purely sensitive nerve that innervates the sole of the foot, or at least parts of the sole, and then redirect it in order to reinnervate a precisely defined new area of skin. The degree of restored human sensory bandwidth can thus be increased via this newly innervated skin area. A so-called phantom limb map is created, where the original organ, in our case the foot, is mapped and also perceived by the patient. This surgically created phantom limb map is then combined with a sensitive device to form a mechanoneural interface (MI) that facilitates the integration of prostheses by amplifying afferent neural signals that transmit sensory information from the external prosthesis back to the CNS.

We operated on the first patient in 2014. Following a left transtibial amputation, the patient suffered from severe drug-dependent phantom limb pain and suicidal thoughts. We exposed the sural nerve on his residual limb and coaptated it proximally above the knee joint to the distal part of the saphenous nerve. This resulted in reinnervation of the sensory information of the sural nerve in the medial part of the residual limb, where the patient could then feel his foot as phantom. He was then fitted with a feedback prosthetic device that could transfer the sense of pressure from the sole of the prosthesis to the newly reinnervated skin area.

After carefully evaluating the results of these first patients, we extended the technique to patients with transfemoral amputations for the first time in 2018 and published the first four case series in 2021 [6]. We observed a significant reduction in pain in all patients, and pain medication could be discontinued, or reduced, to a minimum on demand. The patients showed a significant improvement in gait and balance compared to conventional prostheses. All patients described their physical appearance as normal again. We have now performed this new TSR method on over 55 patients in various centers in Europe.

Based on our successful experience with TSR on the LL, we have further developed the technique to the upper limb (UL). It soon became clear to us that UL loss was more challenging than the loss of the LL. The loss of the hand can lead to a considerable reduction in personal and professional quality of life for any individual and often, inevitably, to psychological consequences. Currently, myoelectric prostheses can restore many of the normal activities of the hand with the exception of authentic tactile sensitivity. In the review article by Shu T. et al [7], all common methods of bionic reconstruction are described in detail. These include TMR, AMI (Agonist-Antagonist Myoneural Interface), RPNI (Regenerative Peripheral Nerve Interface) and TSR. They describe how MIs transmit an afferent neural signal through sensory receptors. Hebert et al demonstrated a widespread and topographic representation of the digits with discrete separation of the median and ulnar hand maps in a defined targeted skin area. This allowed for a preservation of the somatotopy of the digits in three trans humeral amputees after TSR [8].

Résultats

Our talk will present the TSR technique that allows sensations to be perceived precisely at the level of the residual limb in accordance with the new neural circuits that have emerged from neurophysiological research.

The indications for TSR are primarily phantom limb pain, and/or neuropathic pain, that can’t be controlled by conservative therapy or, in the case of elective amputation, its prevention. To date, we have performed TSR in 9 patients. The technique involves neurorrhaphy of the median and ulnar nerves with the lateral and medial antebrachial cutaneous nerves to reinnervate the skin of the residual limb at the forearm. Postoperatively, electroencephalography (EEG) and nerve conduction study (NCS) were performed. There was no phantom limb pain in the electively and acute amputated patients, and in the patients who underwent secondary TSR, the pain decreased significantly or disappeared completely.

In all patients, a phantom limb map of all five fingers (phantom hand) at the level of the residual limb could be regularly visualized. In addition, the patients can distinguish between hot and cold or dry and wet. Somatosensory evoked potentials (SEPs) in EEG and sensory nerve action potentials (SNAPs) in NCS could be derived as a clear reinnervation sign. The redirection of the median and ulnar nerve to the medial and lateral antebrachial cutaneous nerves creates the possibility, with an associated interface, to regain the authentic feeling of the lost hand. Sensors on the fingers transmit a feeling to the reinnervated area of the residual limb. This feedback is given via a noninvasive vibrotactile feedback system, which can be pulled over any prosthetic hand as an “add on”. The phantom pain is suppressed by this constant event-triggered feedback, or it does not occur at all after elective or traumatic amputation [9].

Conclusion

Surgical restoration of existing sensory nerves, using the newly described TSR technique, and the application of a non-invasive sensory feedback system, can provide the brain with new afferent signals. This tricks the brain into believing that the missing limb is still present. This closes the loop in the sensory cortex and phantom pain disappears.

Bibliographie / Références

1. P.L Ephraim, S.T. Wegener E.J. MacKenzie, T.R. Dillingham, L.E. Pezzin. Phantom pain, residual limb pain, and back pain in amputees: Results of a national survey. Arch. Phys. Med. Rehabil, 86, 1910–1919, 2005.
2. M.J Alviar, T. Hale, M. Dungca. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst. Rev., 10, CD006380, 2016.
3. M.A. Pet, J.H Ko, J.L Friedly, P.D Mourad, D.G Smith. Does targeted nerve implantation reduce neuroma pain in amputees? Clin. Orthop. Relat. Res., 472, 2991–3001, 2014.
4. T.A Kuiken, G.A. Dumanian, R.D Lipschutz, L.A. Miller, K.A Stubblefield. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet. Orthot. Int., 28, 245–253 2004.
5. T.A. Kuiken, P.D Marasco, B.A. Lock, R.N Harden, J.P. Dewald. Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation. Proc. Natl. Acad. Sci. USA , 04, 20061–20066, 2007.
6. A. Gardetto, E.M. Baur, C. Prahm, V. Smekal, J. Jeschke, G. Peternell, M.T. Pedrini, J. Kolbenschlag. Reduction of Phantom Limb Pain and Improved Proprioception through a TSR-Based Surgical Technique: A Case Series of Four Patients with Lower Limb Amputation. J Clin Med., 6;10(17):4029. doi: 10.3390/jcm10174029. PMID: 34501477; PMCID: PMC8432479, 2021.
7. T. Shu, G. Herrera-Arcos, C.R Taylor, H.M. Herr, Mechanoneural interfaces for bionic integration. Nature Reviews Bioengineering, doi.org/10.1038/s44222-024-00151-y, 2024.
8. J. S. Hebert, K. M. Chan and M. R Dawson, Cutaneous sensory outcomes from three transhumeral targeted reinnervation cases. Prosthet. Orthot. Int., 40, 303–310, 2016.
9. Gardetto A, Müller-Putz GR, Eberlin KR, Bassetto F, Atkins DJ, Turri M, et al. Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface. J Clin Med, 14(417), 2025. doi 10.3390/jcm14020417.