Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants. Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

The prevalence and risk factors for phantom limb pain: a cross-sectional survey.

BACKGROUND: We previously performed a systematic review and meta-analysis which revealed a Phantom Limb Pain (PLP) prevalence estimate of 64% [95% CI: 60.01-68.1]. The prevalence estimates varied significantly between developed and developing countries. Remarkably, there is limited evidence on the prevalence of PLP and associated risk factors in African populations. METHODS: Adults who had undergone limb amputations between January 2018 and October 2022 were recruited from healthcare facilities in the Western and Eastern Cape Provinces. We excluded individuals with auditory or speech impairments that hindered clear communication via telephone. Data on the prevalence and risk factors for PLP were collected telephonically from consenting and eligible participants. The prevalence of PLP was expressed as a percentage with a 95% confidence interval. The associations between PLP and risk factors for PLP were tested using univariate and multivariable logistic regression analyses. The strength of association was calculated using the Odds Ratio where association was confirmed. RESULTS: The overall PLP prevalence was 71.73% [95% CI: 65.45-77.46]. Persistent pre-operative pain, residual limb pain, and non-painful phantom limb sensations were identified as risk factors for PLP. CONCLUSION: This study revealed a high prevalence of PLP. The use of effective treatments targeting pre-amputation pain may yield more effective and targeted pre-amputation care, leading to improved quality of life after amputation.

Is it really on your hand? Spontaneous sensations are not peripheral sensations - Evidence from able-bodied individuals and a phantom limb syndrome patient.

Among other bodily signals, the perception of sensations arising spontaneously on the skin with no external triggers contributes to body awareness. The topic of spontaneous sensations (SPS) being quite recent in the literature, there is still a debate whether this phenomenon is elicited by peripheral cutaneous units' activity underlying tactile perception or originates directly from central mechanisms. In a first experiment, we figured that, if SPS depended on peripheral afferents, their perception on the glabrous hand should relate to the hand tactile sensitivity. On the contrary, we found no relationship at all, which led us to envisage the scenario of SPS in the absence of cutaneous units. In a second experiment, we present the case of Julie, a right-hand amputee that could perceive and report SPS arising on her phantom limb syndrome. We found that SPS distribution on the phantom limb followed the same gradient as that observed in control participants, unlike SPS perceived on the intact left hand. Those findings are crucial to the understanding of neural factors determining body awareness through SPS perception and provide insights into the existence of a precise neural gradient underlying somesthesis.

Distinct patterns of metabolic motor cortex activity for phantom and residual limb pain in people with amputations: A functional near-infrared spectroscopy study.

BACKGROUND: Phantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although its mechanisms are not completely understood. OBJECTIVES: The aim of this study was to understand, in patients with amputations, the association between PLP and residual limb pain (RLP), and the brain metabolic response in cortical motor circuits, using functional near-infrared spectroscopy (fNIRS). METHODS: Sixty participants were recruited from the rehabilitation program in São Paulo, Brazil. Included patients were aged over 18 years, with traumatic unilateral lower-limb amputation, with PLP for at least 3 months after full recovery from amputation surgery. PLP and RLP levels were measured using visual analogue scales. fNIRS was performed during motor execution and motor mirror tasks for 20 s. In order to highlight possible variables related to variation in pain measures, univariate linear regression analyses were performed for both experimental conditions, resulting in four fNIRS variables (two hemispheres x two experimental conditions). Later, in order to test the topographic specificity of the models, eight multivariate regression analyses were performed (two pain scales x two experimental conditions x two hemispheres), including the primary motor cortex (PMC) related channel as an independent variable as well as five other channels related to the premotor area, supplementary area, and somatosensory cortex. All models were controlled for age, sex, ethnicity, and education. RESULTS: We found that: i) there is an asymmetric metabolic activation during motor execution and mirror task between hemispheres (with a predominance that is ipsilateral to the amputated limb), ii) increased metabolic response in the PMC ipsilateral to the amputation is associated with increased PLP (during both experimental tasks), while increased metabolic response in the contralateral PMC is associated with increased RLP (during the mirror motor task only); ii) increased metabolic activity of the ipsilateral premotor region is associated with increased PLP during the motor mirror task; iii) RLP was only associated with higher metabolic activity in the contralateral PMC and lower metabolic activity in the ipsilateral inferior frontal region during motor mirror task, but PLP was associated with higher metabolic activity during both tasks. CONCLUSION: These results suggest there is both task and region specificity for the association between the brain metabolic response and the two different types of post-amputation pain. The metabolic predominance that is ipsilateral to the amputated limb during both tasks was associated with higher levels of PLP, suggesting a cortical motor network activity imbalance due to potential interhemispheric compensatory mechanisms. The present work contributes to the understanding of the underlying topographical patterns in the motor-related circuits associated with pain after amputations.

A sensory-motor hand prosthesis with integrated thermal feedback.

BACKGROUND: Recently, we reported the presence of phantom thermal sensations in amputees: thermal stimulation of specific spots on the residual arm elicited thermal sensations in their missing hands. Here, we exploit phantom thermal sensations via a standalone system integrated into a robotic prosthetic hand to provide real-time and natural temperature feedback. METHODS: The subject (a male adult with unilateral transradial amputation) used the sensorized prosthesis to manipulate objects and distinguish their thermal properties. We tested his ability to discriminate between (1) hot, cold, and ambient temperature objects, (2) different materials (copper, glass, and plastic), and (3) artificial versus human hands. We also introduced the thermal box and block test (thermal BBT), a test to evaluate real-time temperature discrimination during standardized pick-and-place tasks. FINDINGS: The subject performed all three discrimination tasks above chance level with similar accuracies as with his intact hand. Additionally, in all 15 sessions of the thermal BBT, he correctly placed more than half of the samples. Finally, the phantom thermal sensation was stable during the 13 recording sessions spread over 400 days. CONCLUSION: Our study paves the way for more natural hand prostheses that restore the full palette of sensations. FUNDING: This work was funded by the Bertarelli Foundation (including the Catalyst program); the Swiss National Science Foundation through the National Centre of Competence in Research (NCCR) Robotics; the European Union's Horizon 2020 research and innovation program; the Horizon Europe Research & Innovation Program; the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP); and the Tuscany Health Ecosystem.

Cortical Reorganization after Limb Loss: Bridging the Gap between Basic Science and Clinical Recovery.

Despite the increasing incidence and prevalence of amputation across the globe, individuals with acquired limb loss continue to struggle with functional recovery and chronic pain. A more complete understanding of the motor and sensory remodeling of the peripheral and central nervous system that occurs postamputation may help advance clinical interventions to improve the quality of life for individuals with acquired limb loss. The purpose of this article is to first provide background clinical context on individuals with acquired limb loss and then to provide a comprehensive review of the known motor and sensory neural adaptations from both animal models and human clinical trials. Finally, the article bridges the gap between basic science researchers and clinicians that treat individuals with limb loss by explaining how current clinical treatments may restore function and modulate phantom limb pain using the underlying neural adaptations described above. This review should encourage the further development of novel treatments with known neurological targets to improve the recovery of individuals postamputation.Significance Statement In the United States, 1.6 million people live with limb loss; this number is expected to more than double by 2050. Improved surgical procedures enhance recovery, and new prosthetics and neural interfaces can replace missing limbs with those that communicate bidirectionally with the brain. These advances have been fairly successful, but still most patients experience persistent problems like phantom limb pain, and others discontinue prostheses instead of learning to use them daily. These problematic patient outcomes may be due in part to the lack of consensus among basic and clinical researchers regarding the plasticity mechanisms that occur in the brain after amputation injuries. Here we review results from clinical and animal model studies to bridge this clinical-basic science gap.

Is Phantom Limb Awareness Necessary for the Treatment of Phantom Limb Pain?

Phantom limb pain is attributed to abnormal sensorimotor cortical representations. Various feedback treatments have been applied to induce the reorganization of the sensorimotor cortical representations to reduce pain. We developed a training protocol using a brain-computer interface (BCI) to induce plastic changes in the sensorimotor cortical representation of phantom hand movements and demonstrated that BCI training effectively reduces phantom limb pain. By comparing the induced cortical representation and pain, the mechanisms worsening the pain have been attributed to the residual phantom hand representation. Based on our data obtained using neurofeedback training without explicit phantom hand movements and hand-like visual feedback, we suggest a direct relationship between cortical representation and pain. In this review, we summarize the results of our BCI training protocol and discuss the relationship between cortical representation and phantom limb pain. We propose a treatment for phantom limb pain based on real-time neuroimaging to induce appropriate cortical reorganization by monitoring cortical activities.

Modulations in high-density EEG during the suppression of phantom-limb pain with neurostimulation in upper limb amputees.

Phantom limb pain (PLP) is a distressing and persistent sensation that occurs after the amputation of a limb. While medication-based treatments have limitations and adverse effects, neurostimulation is a promising alternative approach whose mechanism of action needs research, including electroencephalographic (EEG) recordings for the assessment of cortical manifestation of PLP relieving effects. Here we collected and analyzed high-density EEG data in 3 patients (P01, P02, and P03). Peripheral nerve stimulation suppressed PLP in P01 but was ineffective in P02. In contrast, transcutaneous electrical nerve stimulation was effective in P02. In P03, spinal cord stimulation was used to suppress PLP. Changes in EEG oscillatory components were analyzed using spectral analysis and Petrosian fractal dimension. With these methods, changes in EEG spatio-spectral components were found in the theta, alpha, and beta bands in all patients, with these effects being specific to each individual. The changes in the EEG patterns were found for both the periods when PLP level was stationary and the periods when PLP was gradually changing after neurostimulation was turned on or off. Overall, our findings align with the proposed roles of brain rhythms in thalamocortical dysrhythmia or disruption of cortical excitation and inhibition which has been linked to neuropathic pain. The individual differences in the observed effects could be related to the specifics of each patient's treatment and the unique spectral characteristics in each of them. These findings pave the way to the closed-loop systems for PLP management where neurostimulation parameters are adjusted based on EEG-derived markers.

Transcranial magnetic stimulation in the treatment of phantom limb pain: a systematic review.

BACKGROUND: Phantom limb pain (PLP) occurs after amputations and can persist in a chronic and debilitating way. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method capable of influencing brain function and modulating cortical excitability. Its effectiveness in treating chronic pain is promising. OBJECTIVE: To evaluate the evidence on the efficacy and safety of using rTMS in the treatment of PLP, observing the stimulation parameters used, side effects, and benefits of the therapy. METHODS: This is a systematic review of scientific articles published in national and international literature using electronic platforms. RESULTS: Two hundred and fifty two articles were identified. Two hundred and forty six publications were removed because they were duplicated or met the exclusion criteria. After selection, six studies were reviewed, those being two randomized clinical trials and four case reports. All evaluated studies indicated some degree of benefit of rTMS to relieve painful symptoms, even temporarily. Pain perception was lower at the end of treatment when compared to the period prior to the sessions and remained during patient follow-up. There was no standardization of the stimulation parameters used. There were no reports of serious adverse events. The effects of long-term therapy have not been evaluated. CONCLUSION: There are some benefits, even if temporary, in the use of rTMS to relieve painful symptoms in PLP. High-frequency stimulation at M1 demonstrated a significant analgesic effect. Given the potential that has been demonstrated, but limited by the paucity of high-quality studies, further controlled studies are needed to establish and standardize the clinical use of the method.

ANTECEDENTES: A dor do membro fantasma (DMF) ocorre após amputações e pode persistir de forma crônica e debilitante. A estimulação magnética transcraniana repetitiva (EMTr) é um método de neuromodulação não invasivo capaz de influenciar a função cerebral e modular a excitabilidade cortical. Sua eficácia no tratamento da dor crônica é promissora. OBJETIVO: Avaliar as evidências sobre a eficácia e segurança do uso da EMTr no tratamento da DMF, observando os parâmetros de estimulação utilizados, efeitos colaterais e benefícios da terapia. MéTODOS: Trata-se de uma revisão sistemática de artigos científicos publicados na literatura nacional e internacional utilizando plataformas eletrônicas. RESULTADOS: Foram identificados 252 artigos. Duzentas e quarenta e seis publicações foram removidas por estarem duplicadas ou atenderem aos critérios de exclusão. Após a seleção, foram revisados seis estudos, sendo dois ensaios clínicos randomizados e quatro relatos de caso. Todos os estudos avaliados indicaram algum grau de benefício da EMTr no alívio dos sintomas dolorosos, mesmo que temporariamente. A percepção da dor foi menor ao final do tratamento quando comparada ao período anterior às sessões e permaneceu durante o acompanhamento do paciente. Não houve padronização dos parâmetros de estimulação utilizados. Não houve relatos de eventos adversos graves. Os efeitos da terapia a longo prazo não foram avaliados. CONCLUSãO: Existem alguns benefícios, mesmo que temporários, no uso da EMTr para alívio dos sintomas dolorosos na DMF. A estimulação de alta frequência em M1 demonstrou um efeito analgésico significativo. Dado o potencial demonstrado, mas limitado pela escassez de estudos de alta qualidade, são necessários mais estudos controlados para estabelecer e padronizar o uso clínico do método.

Pain and Functional Outcomes following Targeted Muscle Reinnervation: A Systematic Review.

BACKGROUND: It is estimated that by 2050, a total of 3.6 million patients will be living with an amputation in the United States. The objective of this systematic review is to evaluate the effect of targeted muscle reinnervation (TMR) on pain and physical functioning in amputees. METHODS: A literature search was performed on PubMed, Embase, and MEDLINE up to November 28, 2021. Clinical studies assessing the outcomes of TMR (pain, prosthesis control, life quality, limb function, and disability) were included. RESULTS: Thirty-nine articles were included. The total number of patients who underwent TMR was 449, and 716 were controls. Mean follow-up was 25 months. A total of 309 (66%) lower-limb and 159 (34%) upper-limb amputations took place in the TMR group, the most common being below-knee amputations (39%). The control group included a total of 557 (84%) lower-limb and 108 (16%) upper-limb amputations; the greatest proportion being below-knee amputations in this group as well (54%). Trauma was the most common indication for amputation. Phantom limb pain scores were lower by 10.2 points for intensity ( P = 0.01), 4.67 points for behavior ( P = 0.01), and 8.9 points for interference ( P = 0.09). Similarly, residual limb pain measures were lower for cases for intensity, behavior, and interference, but they failed to reach significance. Neuroma symptoms occurred less frequently, and functional and prosthesis control outcomes improved following TMR. CONCLUSION: The literature evidence suggests that TMR is a promising therapy for improving pain, prosthesis use, and functional outcomes after limb amputation.

Primary Targeted Muscle Reinnervation in Above-Knee Amputations in Patients with Unsalvageable Limbs from Limb-Threatening Ischemia or Infection.

BACKGROUND: Amputees frequently suffer from chronic pain in both their residual limbs (RLP) and phantom limbs (PLP) following their amputation. Targeted muscle reinnervation (TMR) is a nerve transfer technique that has been demonstrated to improve pain secondarily and at time of amputation. The goal of this study is to report on the efficacy of primary TMR at time of above-knee level amputations in the setting of limb-threatening ischemia or infection. METHODS: This is a retrospective review of a single-surgeon experience with TMR in patients undergoing through- or above-knee level amputations from January 2018 to June 2021. Patient charts were reviewed for the comorbidities in the Charlson Comorbidity Index. Postoperative notes were assayed for presence and absence of RLP and PLP, overall pain severity, chronic narcotic use, ambulatory status, and complications. A control group of patients undergoing lower limb amputation who did not receive TMR from January 2014 to December 2017 was used for comparison. RESULTS: Forty-one patients with through- or above-knee level amputations and primary TMR were included in this study. The tibial and common peroneal nerves were transferred in all cases to motor branches to the gastrocnemius, semimembranosus, semitendinosus, and biceps femoris. Fifty-eight patients with through- or above-knee level amputations without TMR were included for comparison. The TMR group had significantly less overall pain (41.5 vs. 67.2%, p = 0.01), RLP (26.8 vs. 44.8%, p = 0.04), and PLP (19.5 vs. 43.1%, p = 0.02). There were no significant differences in complication rates. CONCLUSION: TMR can safely and effectively be performed at time of a through- and above-knee level amputation and improves pain outcomes.

Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation.

BACKGROUND: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed). METHODS: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form. RESULTS: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group. CONCLUSIONS: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Graded motor imagery and its phases for individuals with phantom limb pain following amputation: A scoping review.

OBJECTIVE: Three-phase graded motor imagery (limb laterality, explicit motor imagery, and mirror therapy) has been successful in chronic pain populations. However, when applied to phantom limb pain, an amputation-related pain, investigations often use mirror therapy alone. We aimed to explore evidence for graded motor imagery and its phases to treat phantom limb pain. DATA SOURCES: A scoping review was conducted following the JBI Manual of Synthesis and Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews. Thirteen databases, registers, and websites were searched. REVIEW METHODS: Published works on any date prior to the search (August 2023) were included that involved one or more graded motor imagery phases for participants ages 18+ with amputation and phantom limb pain. Extracted data included study characteristics, participant demographics, treatment characteristics, and outcomes. RESULTS: Sixty-one works were included representing 19 countries. Most were uncontrolled studies (31%). Many participants were male (75%) and had unilateral amputations (90%) of varying levels, causes, and duration. Most works examined one treatment phase (92%), most often mirror therapy (84%). Few works (3%) reported three-phase intervention. Dosing was inconsistent across studies. The most measured outcome was pain intensity (95%). CONCLUSION: Despite the success of three-phase graded motor imagery in other pain populations, phantom limb pain research focuses on mirror therapy, largely ignoring other phases. Participant demographics varied, making comparisons difficult. Future work should evaluate graded motor imagery effects and indicators of patient success. The represented countries indicate that graded motor imagery phases are implemented internationally, so future work could have a widespread impact.

Biology and pathophysiology of symptomatic neuromas.

ABSTRACT: Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.

Experience with ultrasound neurography for postoperative evaluation of targeted muscle reinnervation.

Targeted muscle reinnervation (TMR) was originally developed as a means for increasing intuitive prosthesis control, though later found to play a role in phantom limb pain and neuroma prevention. There is a paucity of literature describing the clinical course of patients with poor TMR surgical outcomes and the value of imaging in the postoperative recovery period. This report will illustrate the potential utility of ultrasound neurography to accurately differentiate TMR surgical outcomes in two patients that received upper extremity amputation and subsequent reconstruction with TMR. Ultrasound evaluation of TMR sites in patient 1 confirmed successful reinnervation, evident by nerve fascicle continuity and eventual integration of the transferred nerve into the target muscle. Conversely, the ultrasound of patient 2 showed discontinuity of the nerve fascicles, neuroma formation, and muscle atrophy in all three sites of nerve transfer, suggesting an unsuccessful procedure and poor functional recovery. Ultrasound neurography is uniquely able to capture the longitudinal trajectory of rerouted nerves to confirm continuity and eventual reinnervation into muscle. Therefore, the application of ultrasound in a postoperative setting can correctly identify instances of failed TMR before this information would become available through clinical evaluation. Early identification of poor TMR outcomes may benefit future patients by fostering the discovery of failure mechanisms and aiding in further surgical planning to improve functional outcomes.

Phantom Limb Pain and Painful Neuroma After Dysvascular Lower-Extremity Amputation: A Systematic Review and Meta-Analysis.

BACKGROUND: Phantom limb pain (PLP) and symptomatic neuroma can be debilitating and significantly impact the quality of life of amputees. However, the prevalence of PLP and symptomatic neuromas in patients following dysvascular lower limb amputation (LLA) has not been reliably established. This systematic review and meta-analysis evaluates the prevalence and incidence of phantom limb pain and symptomatic neuroma after dysvascular LLA. METHODS: Four databases (Embase, MEDLINE, Cochrane Central, and Web of Science) were searched on October 5th, 2022. Prospective or retrospective observational cohort studies or cross-sectional studies reporting either the prevalence or incidence of phantom limb pain and/or symptomatic neuroma following dysvascular LLA were identified. Two reviewers independently conducted the screening, data extraction, and the risk of bias assessment according to the PRISMA guidelines. To estimate the prevalence of phantom limb pain, a meta-analysis using a random effects model was performed. RESULTS: Twelve articles were included in the quantitative analysis, including 1924 amputees. A meta-analysis demonstrated that 69% of patients after dysvascular LLA experience phantom limb pain (95% CI 53-86%). The reported pain intensity on a scale from 0-10 in LLA patients ranged between 2.3 ± 1.4 and 5.5 ± .7. A single study reported an incidence of symptomatic neuroma following dysvascular LLA of 5%. CONCLUSIONS: This meta-analysis demonstrates the high prevalence of phantom limb pain after dysvascular LLA. Given the often prolonged and disabling nature of neuropathic pain and the difficulties managing it, more consideration needs to be given to strategies to prevent it at the time of amputation.

Use of virtual reality for the management of phantom limb pain: a systematic review.

PURPOSE: To summarize the research on the effectiveness of virtual reality (VR) therapy for the management of phantom limb pain (PLP). METHODS: Three databases (SCOPUS, Ovid Embase, and Ovid MEDLINE) were searched for studies investigating the use of VR therapy for the treatment of PLP. Original research articles fulfilling the following criteria were included: (i) patients 18 years and older; (ii) all etiologies of amputation; (iii) any level of amputation; (iv) use of immersive VR as a treatment modality for PLP; (v) self-reported objective measures of PLP before and after at least one VR session; (vi) written in English. RESULTS: A total of 15 studies were included for analysis. Fourteen studies reported decreases in objective pain scores following a single VR session or a VR intervention consisting of multiple sessions. Moreover, combining VR with tactile stimulation had a larger beneficial effect on PLP compared with VR alone. CONCLUSIONS: Based on the current literature, VR therapy has the potential to be an effective treatment modality for the management of PLP. However, the low quality of studies, heterogeneity in subject population and intervention type, and lack of data on long-term relief make it difficult to draw definitive conclusions.IMPLICATION FOR REHABILITATIONVirtual reality (VR) therapy has emerged as a new potential treatment option for phantom limb pain (PLP) that circumvents some limitations of mirror therapy.VR therapy was shown to decrease PLP following a single VR session as well as after an intervention consisting of multiple sessions.The addition of vibrotactile stimuli to VR therapy may lead to larger decreases in PLP scores compared with VR therapy alone.

A systematic review of the prevalence of postamputation and chronic neuropathic pain associated with combat injury in military personnel.

ABSTRACT: Combat trauma can lead to widespread tissue damage and limb loss. This may result in chronic neuropathic and post amputation pain, including phantom limb pain (PLP) and residual limb pain (RLP). The military population is distinct with respect to demographic, injury, and social characteristics compared with other amputation and trauma cohorts. We undertook a systematic review of studies of military personnel, with a history of combat injury, that reported a prevalence of any type of postamputation pain or chronic neuropathic pain, identified from Embase and MEDLINE databases.Using the inverse variance method with a random-effects model, we undertook a meta-analysis to determine an overall prevalence and performed exploratory analyses to identify the effect of the type of pain, conflict, and time since injury on prevalence. Pain definitions and types of pain measurement tools used in studies were recorded. Thirty-one studies (14,738 participants) were included. The pooled prevalence of PLP, RLP, and chronic neuropathic pain were 57% (95% CI: 46-68), 61% (95% CI: 50-71), and 26% (95% CI: 10-54), respectively. Between-study heterogeneity was high (I 2 : 94%-98%). Characterisation of duration, frequency, and impact of pain was limited. Factors reported by included studies as being associated with PLP included the presence of RLP and psychological comorbidity. The prevalence of postamputation pain and chronic neuropathic pain after combat trauma is high. We highlight inconsistency of case definitions and terminology for pain and the need for consensus in future research of traumatic injury.