Regaining the intention to live after relief of intractable phantom limb pain: A case study

1 Introduction

Phantom limb pain (PLP), affecting about 64% of the individuals post-amputation [1], is a neuropathic pain perceived as arising from a missing limb. Chronic PLP, lasting over 3 months [2], often diminishes participation and quality of life in individuals with an amputation [3,4,5] and has been associated with increased anxiety, stress, sleep deficiency, and depression [6,7]. Further, chronic pain more than doubles the odds of suicidal intentions, behaviors, or suicide attempts [8,9,10]. Recent research involving over 44,000 individuals who had undergone leg amputations found that those diagnosed with PLP were significantly more likely to experience psychiatric comorbidities, including suicidal thoughts, depression, and anxiety, compared to those without PLP [11].

In countries like the Netherlands, euthanasia, where a third party administers drugs to end a person’s life at their voluntary and competent request [12,13], is legal for alleviating physical or mental suffering, including chronic pain from conditions like cancer and neuropathic pain [13,14,15,16,17]. Requests for euthanasia in the Netherlands must undergo a comprehensive assessment by an independent End-of-Life (EOL) clinic to evaluate decision-making capacity, rule out treatable psychiatric conditions, confirm that all reasonable treatment options have been exhausted, and include an independent medical consultation from a trained psychiatrist [18,19].

Several treatments for PLP have been explored, but none have definitively and successfully alleviated the various PLP cases [20,21]. Phantom motor execution (PME) is a novel treatment utilizing myoelectric pattern recognition from residual limb muscle signals to control virtual reality (VR) and augmented reality (AR) environments in which serious gaming is employed to promote the movement of the phantom limb [22,23,24]. A multicenter, double-blind, randomized clinical trial (RCT) evaluated PME’s effectiveness in alleviating PLP across eight countries and ten institutions, including The University Medical Center Groningen in the Netherlands (UMCG) [23,25]. The control group was treated with phantom motor imagery (PMI), where participants only imagined the phantom movements while observing them in a VR environment [23,25].

At UMCG, an exceptional case emerged in the PMI group. A participant referred to as “MB” (pseudonym) had experienced intractable chronic PLP for several years following a transfemoral amputation and was already engaged in the formal euthanasia process through an EOL clinic due to the unbearable and untreatable nature of his pain when he chose to join the RCT as a last resort to relieve his suffering. Positive results were observed during the RCT after the training protocol [23]; however, his PLP returned at the 1-month follow-up, and so did his intention to continue the euthanasia process. Considering the seriousness of the case, MB was removed from the RCT, discontinued the follow-up assessment [23], and was given a customized PMI software for independent home training.

In this study, we aimed to explore the severity and daily life consequences of PLP before, during, and after PMI treatment at the clinic and home in a person with chronic PLP. Furthermore, we explored how the PMI treatment influenced this individual’s life and his decision regarding euthanasia.

2 Methods

This mixed-method design included quantitative and qualitative data [26,27]. Quantitative data on PLP and quality of life were collected during the RCT until the 1-month follow-up [23,25] and 6 months and 1 year after the beginning of the PMI home training. Additionally, a semi-structured interview was conducted 6 months after the PMI home training began (Figure 1). The ethical committee of the UMCG approved and provided a waiver prior to the start of the study, as it was not considered clinical research involving human subjects as defined by the Dutch Medical Research Involving Human Subjects Act (file number METc 2021/437). Informed consent was obtained from the participant prior to participation in the PLP RCT study and this case study. This study follows the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist [28] and Case Report guidelines (CARE) [29].

Figure 1

Timeline assessments. Abbreviations: PLP, phantom limb pain; RCT, Randomized Clinical Trial; PMI, phantom motor imagery; Q-PLP, Questionnaire about Phantom Limb Pain; PDI, Pain Disability Index; EQ-5D, European Quality of Life 5 Dimensions; PSEQ-2, Pain Self-Efficacy Questionnaire; PCS-6, Pain Catastrophizing Scale; PHQ-2, Patient Health Questionnaire-2 (PHQ-2); FU; follow-up; m, month.

2.2 Intervention

MB underwent two PMI training phases: PMI treatment according to the RCT study protocol until the 1-month follow-up and self-administrated PMI home training, 4 months after the last session of the RCT (Figure 1).

2.2.1 RCT trial, PMI-guided treatment

MB joined the RCT in October 2020. Severe depression or suicidal ideation were not exclusion criteria for joining the RCT, but a thorough pre-study clinical evaluation took place regarding MB’s capability of giving informed consent and being able to comply with the study protocol. Subsequently, MB completed a 15-session protocol twice a week with guidance from a clinician trained in PMI treatment.

PMI consisted of participants imagining moving their phantom limb in synchrony with a virtual limb moving on a computer screen (Figure 2) [23,25]. For those in the control group of the RCT, surface electrodes were applied to monitor EMG activity. If the electrodes detected muscle contractions, the VR program would pause and display a warning message instructing the user to relax and focus solely on imagining the movements. The user must acknowledge this warning to allow the software to resume execution, ensuring adherence to the RCT training protocol [23,25].

Figure 2

PMI training setup during RCT. Upper panel: The patient imagines the movements of his phantom limb based on the movements shown on the screen. Surface electrodes were positioned to ensure that the participant did not engage in actual muscle contractions. If muscular activity was detected, the VR program automatically paused and displayed a warning message, instructing the participant to relax and focus exclusively on motor imagery. Lower panels: The software includes four training steps guiding different degrees of freedom of several phantom movements: VR, target achievement control (TAC), AR, and several serious games. Source: Illustration by Mirka Buist.

2.2.2 Home training, PMI self-administered treatment

Customized PMI software was installed on MB’s computer, where no electrodes or devices were required for its operation. He was instructed to use the software at home and encouraged to train twice weekly for at least 30 min per session, with the freedom to choose the training frequency and movements. As MB was familiar with the PMI software, the researchers only sporadically contacted him to confirm everything was working.

3 Results

3.1 RCT and home training assessments

3.1.1 Primary outcome

Similar patterns were observed for the Q-PLP questions related to PLP intensity, sleep, and daily life activities (Figure 3). Initially, high PLP interference was seen, gradually decreasing until session 15. At the 1-month follow-up, scores increased, but home training reduced PLP and its impact on daily life to zero, maintaining long-term improvement.

Figure 3

Phantom limb pain questionnaire (Q-PLP). The intensity of PLP, interference with sleep, and daily activities (blue, orange, and gray lines, respectively) are depicted for all treatment sessions during the RCT, the 1-month follow-up assessment, and the home training. Abbreviations: PLP, phantom limb pain; M, months; Y, year, FU, follow-up; s, session; RCT, randomized clinical trial; PMI, phantom motor imagery.

3.1.2 Secondary outcomes

PDI, PCS-6, and PHQ-2 showed similar tendencies across visits (Figure 4a). Fluctuations in scores were observed across phases; however, an overall decreasing trend suggested a reduced impact of PLP following PMI.

Figure 4

Assessments – secondary outcomes. (a) PDI (blue line), PCS-6 (orange line), and PHQ-2 (gray line) scores as assessed during the RCT, at 1-month follow-up, and during home use: lower scores are better scores. (b) PSEQ-2 (green line) and EQ-5D-5L (blue line) scores as assessed during the RCT, at 1-month follow up and during home use: higher scores are better scores. Abbreviations: Pain Disability Index; PSEQ-2, Pain Self-Efficacy Questionnaire; PCS-6, Pain Catastrophizing Scale – 6; PHQ-2, Patient Health Questionnaire-2; EQ-5D-5L, European Quality of Life 5 Dimensions; q6: question 6; PMI, phantom motor imagery; FU, follow-up; m, months; PLP, phantom limb pain; RCT, randomized clinical trial; VAS, visual analog scale.

PSEQ-2 and EQ-5D-5L (Figure 4b), initially low, increased by over 20 points after session 15. Despite a decline at the 1-month follow-up, scores increased during PMI home training, indicating an overall positive trend and better outcomes.

4 Discussion

This mixed-method study exemplifies how complex, severe, and chronic PLP can be, leading a person to even consider ending their life to conclude their suffering. In this case study, PMI was the first intervention to alleviate the participant’s chronic PLP, first in a clinical setting and then in a home setting, after several years of unsuccessful treatments. This reduction in PLP had a positive impact on all aspects of the participant’s life, especially on sleep and daily activities, which are common aspects disrupted due to PLP. While this is an extraordinary case, further and more extensive research is needed to investigate the effectiveness of PMI and explore solutions for the unresolved PLP cases.

PLP is a complex and poorly understood condition [22,40], making PLP difficult for people with amputation and clinicians to comprehend, manage, and treat [41,42]. A study investigating healthcare professionals’ views on PLP indicated that only a few professionals felt they fully understood PLP, leading to inconsistent and insufficient patient information [42]. Similarly, people with amputation consider that PLP is not always accurately explained by clinicians, stressing the need for early education after amputation [41]. The present study is an example of this fact, in which the participant struggled to understand his PLP for more than 9 years (until the RCT). Understanding and contextualizing chronic pain through psychoeducation has been shown to reduce pain-related distress, enhance coping with pain, and decrease pain catastrophizing [43,44,45]. In the context of PLP, where the affected limb is not visible, education that includes an explanation of the neurophysiological mechanisms of pain may help individuals make sense of their experience and feel less isolated. Furthermore, the therapeutic relationship and empathetic understanding from clinicians have been shown to positively influence treatment outcomes in chronic pain by promoting trust, validation, and adherence to self-management strategies [46,47]. This was evident in the present study, where the participant reported a positive experience with the therapist’s supportive and understanding approach during the PMI training conducted at the hospital. These findings emphasize the need to enhance PLP-related education for both clinicians and individuals with amputations.

This case study demonstrates the profound and multidimensional impact PLP could have on an individual’s life, affecting biological, psychological, and social factors [48]. As seen in this case, PLP can create a persistent, negative cycle of chronic pain, emotional distress, and social isolation so severe that it can lead a person to consider euthanasia as a means of escaping the suffering. In this unique case, PMI helps disrupt this negative loop, leading to significant improvements across all aspects of the individual’s life and restoring their will to live. However, it is important to emphasize that this is an exceptional case. While the outcome was undoubtedly positive, the findings must be interpreted with caution and within the ethical and contextual boundaries of a single-case design. Such an individual experience may not be generalizable to all persons suffering from PLP or experiencing suicidal ideation due to chronic pain. The participant’s decision to discontinue the euthanasia process was personal and shaped by his biopsychosocial context. Still, while this case cannot serve as a broadly applicable clinical precedent, it offers valuable insights into the multidimensional factors that must be considered when treating PLP.

This case study is the first to incorporate PMI at home, showing it is a feasible self-administered intervention and may lead to a long-lasting reduction in PLP. The participant described enjoying the training at home more than in the clinic, appreciating the flexibility in the training schedule, the absence of commuting, improved concentration, and reduced pressure, indicating the potential benefits PMI could offer in a home environment. A previous study on PME home use also indicated to be a feasible intervention, however, with variable adherence due to challenges like electrode placement and system complexity [49]. In contrast, PMI for home use does not require electrodes or hardware, simplifying the process, reducing complications, eliminating the need for clinical assistance, and lowering costs. Hence, this case study shows that PMI appears as an enjoyable, practical, and cost-effective home solution. Its potential for high adherence and long-term use makes it a promising intervention for reducing PLP. However, further research is necessary to investigate these outcomes and better understand their long-term effects.

After amputation, people often feel their phantom limbs are immovable [19,36]. PMI seemed to have enabled the participant to move his phantom limb. The participant perceived a direct relation between control of the phantom movements and pain reduction, especially when mastering distal joint movements. This is consistent with preliminary evidence showing an inversed correlation between phantom limb movement and PLP [22,50,51]. These findings suggest that people with an amputation might benefit from trying to keep their phantom limbs mobile to prevent or reduce PLP [50,51].

Further research is needed to investigate PMI’s effectiveness and its relation to PLP reduction [22]. However, as noted by the participant in this case study, visual feedback seems to play a crucial role in imagining phantom movements. Previous evidence suggests that combining action observation (watching a movement) with imagination enhances motor-related brain activity more effectively than either activity alone [52,53,54,55]. Another element described by the participant was the relationship between an increased sense of ownership of the phantom and a reduction in PLP, which is consistent with previous studies showing that greater prosthesis ownership is related to lower PLP [56]. Although this single case provides valuable experiential insights, it does not allow for definitive conclusions about the underlying neurophysiological mechanisms of PMI, nor on the role of non-specific effects (education, bonding with therapists, etc.), and so discussion of potential processes should be considered exploratory and should be investigated further in future research.

This study’s strength lies in its combination of quantitative and qualitative data, providing a comprehensive overview of the case. Qualitative data collection and analysis were performed by independent researchers not involved in the intervention, ensuring the trustworthiness of the findings through triangulation and consensus among researchers [57]. A limitation of this study is that data represent only one case, which may not represent all people suffering from PLP. Additionally, the absence of long-term follow-up limits the extent to which the durability of the restored will to live can be evaluated.

5 Conclusion

This study shows that PLP can be chronic and severe enough to lead someone to pursue euthanasia. PMI appeared to be a promising intervention to decrease PLP, and in this particular case, it motivated the discontinuation of the euthanasia process and restored the will to live in a person with chronic PLP. The findings suggest PMI is also a feasible and enjoyable intervention for home and self-administered training, leading to long-term PLP reduction. This study encourages further investigation of PMI in home and clinical settings, and its effect on chronic PLP. Furthermore, the study highlights the importance of qualitative research to deepen the understanding of PLP and emphasizes the need for enhanced PLP education among clinicians and people with amputation.