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Rehabil Oncol. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: Rehabil Oncol. 2016 July ; 34(3): 104–110.
Mirror Therapy for Phantom Limb Pain at a Pediatric Oncology Institution Doralina L. Anghelescu, MD [Member], Department of Pediatric Medicine, Division of Anesthesiology, Director, Pain Management Service, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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Cassandra N. Kelly, BS [Pediatric Oncology Education Student], St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Brenda D. Steen, MNS [Clinical Research Associate], Department of Anesthesiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Jianrong Wu, PhD [Associate Member], Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Huiyun Wu, MS [Senior Biostatistician], Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Brian M. DeFeo, DPT, OCS [Physical Therapist], Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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Kristin Scobey, DPT, PCS [Director], and Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Laura Burgoyne, BM, BS [Senior Staff Specialist] Children’s Anaesthesia, Women’s and Children’s Hospital, North Adelaide SA 5006, Australia
Abstract Background and Purpose/Objective—Mirror therapy has not been reported for phantom limb pain (PLP) in pediatric oncology. Our aims are to describe the incidence and duration of PLP post-amputation, the duration of follow-up, pain scores and pain medications, and the differences between a group that received mirror therapy (MT) in addition to the standard treatment and a group that received only the standard treatment (non-MT).
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Methods—A retrospective review of patients’ medical records from June 2009 to March 2015 was completed. The demographic characteristics, diagnoses and types of surgery were collected. The incidence and duration of PLP, duration of pain service follow-up, pain medications and pain scores were collected and analyzed using the Wilcoxon rank sum test. Results—Of 21 patients who underwent amputations (median age 13 years, range, 8–24 years), most common primary diagnosis osteosarcoma), 18 (85.7%) experienced PLP; 38.9% of them
Corresponding Author: Doralina L. Anghelescu, MD, Division of Anesthesiology, MS 130, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA, Phone: 901-595-4032, FAX: 901-595-4061, [email protected]. Disclosures: The authors have no conflicts of interest to disclose.
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experienced PLP at 1 year post-amputation (11.1% of the MT group and 66.7% of the non-MT group). The MT group and non-MT groups experienced PLP for a mean (± SD) of 246 (± 200) days, and 541 (± 363) days, respectively (p=0.08). The mean (SD) opioid doses (mg/kg/day) in the MT and non-MT groups were 0.81 (± 0.99) and 0.33 (± 0.31), respectively; the mean (SD) gabapentin doses (mg/kg/day) were 40.1 (± 21) for the MT group and 30.5 (± 11.5) for the nonMT group. Conclusion—MT in children with cancer-related amputations is associated with lower incidence of PLP at 1 year and shorter duration of PLP. Keywords mirror therapy; phantom limb pain; pediatric oncology
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BACKGROUND Phantom Limb Pain in the General Population
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Phantom limb pain (PLP), the sensation of pain experienced in a limb that is no longer there, is a very common result of limb amputation.1 According to the literature, 60% to 90% of amputees experience PLP at some point in their lifetime.2 Phantom limb pain can occur whether the amputation is traumatic or surgical, and the incidence is generally higher after a traumatic loss or if there is a pre-existing painful condition, as opposed to a planned surgical amputation of a non-painful limb.3 Most commonly, PLP has an early onset; nevertheless, it can appear months or even years after the amputation. In 50% of patients who experience PLP, the symptoms develop immediately post-amputation, and in about 75%, PLP symptoms develop within 24 hours.4 Although the exact mechanism of PLP is still not fully understood, this phenomenon is widely thought to be related to conflicting input from motor, visual, sensory, and proprioceptive systems.5 It has been shown that there is an increased risk for PLP if the patient is female, has an upper extremity amputation, there is presence of pre-amputation pain, or if there is residual pain in the remaining limb.6 The incidence of PLP is thought to be lower in children than in adults, and PLP has not been reported in children younger than 4 years.1 Phantom Limb Pain in the Pediatric Oncology Population
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In a study of children and young adults (ages 6–27 years, of which 64% were younger than 18 years) with cancer-related surgical amputations, 64% suffered pre-amputation pain; 76% experienced PLP within the first year after amputation; and 10% experienced PLP at 1 year post-amputation.7 The study evaluated factors to predict PLP, and although all patients who experienced PLP 1 year after amputation were older than 18 years, had pre-amputation pain, and had a proximal limb amputation, none of these factors were statically significant, possibly due to the small sample size.7 Patients who undergo pediatric cancer–related amputations have a higher incidence of PLP (90%) than the pediatric amputation population as a whole (83%).8
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Mirror Therapy for Phantom Limb Pain
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A non-pharmacological intervention for PLP is mirror therapy (MT). After an amputation, an extensive reorganization of the sensorimotor cortex takes place, and the extent of cortical reorganization and the intensity of PLP are positively correlated.9 The aim of MT is to reverse the maladaptive reorganization within the sensorimotor cortex, thereby reducing PLP. MT consists of placing a mirror medial to the intact limb and allowing the patient to view a reflection of their anatomical limb in the visual space occupied by the phantom limb.10 Patients can move or touch their anatomical limb while looking into the mirror and visualizing both limbs doing the same action. MT is thought to provide the link between the visual and motor systems that is missing in PLP. MT was developed by Ramachandran and Rogers-Ramachandran in 1996; in their study, all of the subjects who received MT experienced a reduction in PLP.11
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Studies have shown variable success rates of MT for PLP12–14. Better effects were noted when MT was used to treat deep somatic pain, pressure, and proprioception than to treat superficial pain, and temperature sensitivity; this is due to the fact that deep tissues integrate sensorimotor nerves and create movements, while superficial tissues do not.15 MT has been integrated into the treatment of amputees, especially when other treatments such as pain medication, nerve blocks, physical therapy, and local anesthetics have been unsuccessful. Several factors have been evaluated for predictive value of success with MT, including preamputation pain, time between the amputation and beginning of MT, presence of telescoping sensation, distal vs. proximal amputations, and upper-vs. lower-extremity amputations.1,2
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Furthermore, although MT has been used for the past 2 decades in adults, no firm conclusion can be drawn regarding its effects for PLP in adults,12,14 furthermore, its efficacy has yet to be evaluated in children, adolescents, and young adults. The goal of this retrospective study was to describe the differences between pediatric patients who received MT in addition to the standard therapy for PLP (MT group) and those who received only the standard therapy (non-MT group) at our institution. The following outcome measures were assessed: duration of PLP, intensity of PLP, pain medications used and their dose regimens.
METHODS Patients and Medical Records Review
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This retrospective study included all patients who underwent an amputation at a pediatric oncology institution between June 2009 and March 2015, identified from the institution’s surgical database, including ages up to 24 years (children, adolescent and young adult) and all diagnoses. This study was approved by the Institutional Review Board. The information obtained from the medical records included demographic data, pain medication data, and pain score data. The demographic data collected included date of birth, age at the time of amputation, sex, race, and weight. Primary diagnosis, surgical procedure, date of surgical procedure, number of days of follow-up by the pain service, number of days with PLP, and date of MT initiation and/or number of sessions, if applicable, were also collected from the patients’ medical records. Time points for data collection for pain scores and pain medications included: postoperative days (PODs) 1 through 6, weeks 2 to 4, and Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
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months 2 to 6, or until the PLP resolved and/or the patient was discharged from the pain service, whichever occurred last. The daily data for PODs 1 through 6 were analyzed as one data point for Week 1. Medical records were also examined to determine if nonpharmacological interventions for pain were provided by the Psychology Service. Pain Scores Review
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During the chart review process, data collection regarding pain scores pertained to the diagnosis of PLP, while other sources and types of pain (i.e., stump pain, post-operative pain or localized neuroma after amputation) were excluded from the data collection. Specifically, the diagnosis of PLP was present if pain was described in the absent amputated extremity; perception of non-painful sensations in the absent extremity did not constitute PLP. A standard 11 point Numerical Pain Score (0–10) was used to assess pain throughout hospitalization and at outpatient visits. Pain scores were collected from the pain service notes, physical therapy notes, and nursing notes daily during hospitalization and on days of pain clinic visits in the outpatient setting. Mirror Therapy Data Review
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Patients were referred to physical therapy at the discretion of the referring surgeon with the specific indication to evaluate for MT and train in the use of MT as indicated. The time of the first MT session was dependent upon patient’s first reported symptoms of PLP, either at the initial evaluation or at follow up treatment sessions. During the initial physical therapy consult, symptoms were assessed, including PLP. Patients who reported PLP were provided with MT by a licensed physical therapist. The MT session consisted of placing the patient’s residual limb in a mirror box triangle with instructions to perform simple exercises such as ankle pumps, ankle circles, and quadriceps contractions while viewing both the intact extremity and its mirror reflection. The patients were encouraged to perform exercises bilaterally, imagining two intact extremities with visual feedback provided by the mirror box. Upon completion of initial MT session, patients were provided the mirror box and were advised to perform MT as needed as a home exercise program; patients were also scheduled for physical therapy follow up treatment sessions. At each follow up session, the history of PLP, the use of MT per home exercise program, and any changes in PLP following MT were reviewed. Patients were asked to report any PLP during the session, followed by therapistled MT if indicated. Patients that denied any recent symptoms of PLP received no further MT. The duration of MT sessions was individually based; patients were allowed to stop upon relief of pain or upon tiring of activity, usually following some decrease in pain. The frequency of MT sessions was dependent upon the frequency PLP episodes. Patients were advised to perform MT with every occurrence of PLP, up to several times per day, until experiencing no further symptoms. Pain Medication Data Review The pain medication data collected included doses and duration of treatment for opioids (including use of patient-controlled analgesia), gabapentin, amitriptyline, methadone, continuous peripheral nerve blocks, and epidural infusions. The medication administration record was the source for pain medications given while the patient was hospitalized, and the pain service notes provided additional pain medication data during the inpatient course and Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
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follow-up outpatient visits. The amount of “as needed” (PRN) medications used for pain was determined based on the pain diary or pain medication inventory from each pain service outpatient visit. The pain diaries provided direct data regarding the dose regimen and number of doses taken daily for pain. The pain medication inventory provided data on the number of remaining doses available and the number of doses prescribed for each pain medication during pain service outpatient visits. Equianalgesic conversion rates were used to convert opioid medications into intravenous (IV) morphine equivalent doses (MEDs), as milligram per kilogram per day (Table 1). The patient’s weight noted for dose calculations was the first available weight after amputation, and this value was used throughout the duration of the data collection. Statistical Analysis
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Pain scores, pain medication data, duration of NP medication use, duration of NP, and duration of continuous epidural and nerve-block infusions were analyzed and reported as descriptive statistics: mean (± SD) and median (range), in the MT group and non-MT group. The Wilcoxon rank sum test was used to examine the difference in distribution of durations, dose, and pain score between MT group and non-MT group. Multiple comparisons over different time points were adjusted for using the False Discovery Rate (FDR) method. All tests were 2-sided and the significance level was set at 0.05. All the computations were done using SAS software version 9.3 (SAS Institute Inc., Cary, NC, USA).
RESULTS Patient Characteristics
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Between June 2009 and March 2015, 21 patients under age 24 years underwent 21 amputations at our institution; 18 of them (85.7%) experienced PLP. The study outcomes presented here pertain to the 18 patients who developed PLP. Of the 18 patients with PLP, 9 received MT and 9 did not. The following number of patients contributed to each pain outcome analyzed, as described in the flow diagram (Figure 1): 1) incidence of PLP (n=18), 2) pain scores for PLP and pain medications (n=17), 3) duration of PLP and duration of follow up (n=15). As noted in the flow diagram (Figure 1), 1 patient was lost for follow up due to transfer to another institution at 4 weeks postoperatively; therefore, his data did not contribute to the duration of PLP or duration of follow-up by the pain service. This patient had not received MT interventions for PLP by the time of transfer. One patient in the MT group was still receiving treatment for PLP at the closing date for data collection for the study; therefore, his data did not contribute to the duration of PLP or duration of follow-up by the pain service. One patient in the MT group was excluded from analysis for all pain outcomes (i.e, pain medications, pain scores, duration of PLP and duration of follow up) because the clinical scenario was that of an amputation 2 weeks after a limb-sparing operation, followed by another surgical procedure during the course of the study, which confounded the post-amputation pain-outcome measures; his data contributed to the incidence and the demographic analysis. The median age of the patients was 13 years (range, 8–24 years), and the most common primary diagnosis was osteosarcoma. The demographic data and patient characteristics,
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including diagnoses and types of surgical amputations, for the entire cohort and the MT and non-MT groups are presented in Table 2. In this cohort, 18 (85.7%) experienced PLP; overall, 7 of 18 patients (38.9%) still had unresolved PLP at 1 year post-amputation, with a higher incidence of PLP in the non-MT group: 6 of 9 patients in the non-MT group (66.7%) vs. 1 of 9 patients in the MT group (11.1%). Mirror Therapy In 9 patients who received MT, the timing of therapy initiation varied; according to the physical therapists’ notes, MT was initiated when PLP started and was prescribed “as needed” for PLP. Proper techniques were taught at the beginning of physical therapy, and patients were instructed to continue the MT at home, whenever the PLP was bothersome. Seven patients with complete MT data received an average of 4 MT sessions with the physical therapists and an unknown number of sessions at home.
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Duration of Phantom Limb Pain and Follow-up by the Pain Service Patients in the non-MT group experienced a longer duration of PLP than the patients in the MT group. The mean duration of PLP was 246 days (± 200 days) for the MT group and 541 days (± 363 days) for the non-MT group (p=0.08), respectively (Figure 2 and Table 3). The MT and non-MT groups had a mean duration of follow up by the pain service of 84 days (± 46 days) and 77 days (± 37 days), respectively (p=0.77) (Table 3). The PLP eventually resolved in all study subjects. Pain Medications
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The mean opioid doses expressed as MED in the MT and non-MT groups for the overall duration of treatment were 0.81 mg/kg per day (± 0.99 mg/kg per day) and 0.33 mg/kg per day (± 0.31 mg/kg per day), respectively. Although the MT group received higher doses at all data points in time, none of the differences reached statistical significance. The mean gabapentin doses for the overall duration of treatment were 40.1 mg/kg per day (± 21 mg/kg per day) for the MT group and 30.5 mg/kg per day (± 11.5 mg/kg per day) for the non-MT group. We found no significant differences in gabapentin doses at any data points. Amitriptyline and methadone doses were not statistically analyzed because of the insufficient amount of data. Nine of the 17 patients with PLP were treated with amitriptyline (6 in the MT group and 3 in the non-MT group), and 5 received methadone treatment (4 in the MT group and 1 in the non-MT group).
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Continuous nerve blocks or epidural infusions were administered for a mean of 5.1 days (± 4.7 days) for the entire cohort, 5.1 days (± 2.9 days) for the non-MT group, and 5 days (± 6 days) for the MT group. All patients, except one in the MT group, received nonpharmacologic interventions for pain from a clinical psychologist. For most patients, the psychology consultation was provided before the amputation and continued post-amputation for several sessions.
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Pain Scores
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The differences between the pain scores in the MT group and non-MT group were not significant at any data point (adjusted p-value = 1.0) (Table 4).
DISCUSSION This is the first report on the use of MT for PLP in children, adolescents, and young adults post-amputation and specifically to investigate the differences in incidence and duration of PLP, duration of follow-up by the pain service, pain medication doses and pain scores.
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The main differences between the MT and non-MT groups were a longer duration of PLP and a higher incidence of PLP in the non-MT group at 1 year post-amputation. The non-MT group had PLP for more than twice as long as the MT group, and the incidence of PLP in the non-MT group at 1 year was 66.7%% vs. 11.1% in MT group. MT did not appear to be associated with a reduction in the use of medications, either opioid or neuropathic pain– specific medications (gabapentin, amitriptyline, and methadone) or lower pain score. A possible explanation for these findings is selection bias, as patients who experienced more severe PLP may have been more likely to be directed to have physical therapy evaluation and treatment with MT. The patients with more severe pain may have “self-selected” to receive MT in addition to the standard pharmacologic and non-pharmacologic therapies; these patients also received higher doses of opioid and gabapentin, which is suggestive of clinical scenarios of more difficult to control pain. Additionally, the MT group included 2 cases of proximal amputations (a forequarter amputation and an external hemipelvectomy), which are more likely to be associated with increased severity and duration of PLP.
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The overall incidence of PLP we report here is within the range of PLP incidence reported by other pediatric studies. Eighteen of 21 (85.7%) patients experienced PLP within the first year following their amputations, and 38.9% of those patients had persistent PLP at 1 year post-amputation. Our findings are consistent with those of the study by Krane et al. which found that over a 10-year period, 90% of pediatric cancer–related amputations resulted in PLP8, and they are slightly higher than the findings of the study by Burgoyne et al., which reported that 76% of patients had PLP, and only 10% experienced PLP that persisted at 1 year post-amputation.7
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Due to the retrospective design of this study and the fact that each patient had many concurrent interventions for pain, our findings do not conclusively indicate that MT contributed to the difference in incidence of PLP at 1 year or duration of PLP. Furthermore, the use of higher doses of opioids and gabapentin in the MT group is suggestive of more severe pain in this group. A limitation of our study is the specific modality of delivering MT. The literature reporting MT outcomes describes the use of prescribed MT on a scheduled basis, such as sessions of 30 min/day, 5 days/week, for 3 weeks.10 This is seemingly most effective for reversing the maladaptive cortical reorganization that occurs after an amputation. The use of MT “as needed,” rather than on a scheduled basis, may have been less effective in reducing the duration and intensity of the PLP. It is reasonable to hypothesize that in order to be effective,
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MT should be done consistently. Another limitation of our MT data is the lack of documentation on the frequency and duration of MT regimens continued at home. The actual use of MT at home is not known and may have been inconsistent, as there was no assurance of compliance. Currently, the literature is conflicting as to whether the timing of MT initiation is a crucial factor in its success. The fact that MT initiation dates were variable in our study group affects the strength of the outcome data.
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One must also be cognizant of the dissimilarity between the clinical characteristics of the 2 groups: the MT group included 7 above-knee amputation (AKA) cases, 1 hemipelvectomy, and 1 forequarter amputation, and the non-MT group included 6 AKA cases, 2 below-knee amputations (BKA), and 1 below-elbow amputation (BEA). Proximal amputations are associated more frequently with PLP than are distal amputations.1 By their nature, the hemipelvectomy and the forequarter amputation are much more painful procedures with more difficult recovery periods. Patients who undergo those surgeries are expected to require higher consumption of pain medications than are those who undergo more distal amputations. This dissimilarity may have contributed to the higher pain medication consumption in the MT group. Another difference was that the median age of the MT group (12 years) was younger than that of non-MT group (16 years), which also could have influenced the results.
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Patients in the MT group received higher doses of opioids and gabapentin than did those in the non-MT group, from the beginning of the study period, even before MT interventions were initiated. The dose regimens of those medications may be associated with the severity of both nociceptive postoperative pain and PLP. These findings suggest that the patients in the MT group experienced more severe nociceptive postoperative pain and PLP than did the patients in the non-MT group, despite the lack of disparity in pain scores. Of note, the use amitriptyline, and methadone post-amputation, in addition to opioids and gabapentin, usually reflects a need to address the symptoms of PLP by adding second (tricyclic antidepressant) and third line (methadone) therapies for PLP; while the consumption of opioids cannot be attributed with certainty to the need to treat PLP (neuropathic pain) vs. nociceptive postoperative pain, during the immediate-postoperative period. In conclusion, the MT group did experience a shorter duration of PLP and lower incidence of PLP at 1 year, when compared to the non-MT group. The findings of this study highlight the need for prospective, randomized studies of MT vs. non-MT groups of pediatric, adolescent and young adult patients with PLP.
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Funding: This study was supported in part by the National Cancer Institute Cancer Center Support Core Grant 5P30CA-21765-32, National Cancer Institute Grant 5R25CA23944, and ALSAC, neither of which had a role in its planning, conduct, analysis, or reporting.
REFERENCES 1. Pirowska A, Wloch T, Nowobilski R, Plaszewski M, Hocini A, Menager D. Phantom phenomena and body scheme after limb amputation: A literature review. Neurol Neurochir Pol. 2014; 48(1):52– 59. [PubMed: 24636771]
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2. Foell J, Bekrater-Bodmann R, Diers M, Flor H. Mirror therapy for phantom limb pain: brain changes and the role of body representation. Eur J Pain. 2014; 18(5):729–739. [PubMed: 24327313] 3. Hanling SR, Wallace SC, Hollenbeck KJ, Belnap BD, Tulis MR. Preamputation Mirror Therapy May Prevent Development of Phantom Limb Pain: A Case Series. Anesth Analg. 2010; 110(2):611– 614. [PubMed: 19917622] 4. Kim SY, Kim YY. Mirror Therapy for Phantom Limb Pain. Korean J Pain. 2012; 25(4):272–274. [PubMed: 23091690] 5. Schmalzl L, Ragno C, Ehrsson HH. An alternative to traditional mirror therapy: illusory touch can reduce phantom pain when illusory movement does not. Clin J Pain. 2013; 29(10):e10–e18. [PubMed: 23446074] 6. Subedi B, Grossberg G. Phantom Limb Pain: Mechanisms and Treatment Approaches. Pain Res Treat. 2011; 2011:1–8. 7. Burgoyne LL, Billups CA, Jiron JL Jr, et al. Phantom limb pain in young cancer-related amputees: recent experience at St Jude children's research hospital. Clin J Pain. 2012; 28(3):222–225. [PubMed: 21785344] 8. Krane EJ, Heller LB. The prevalence of phantom sensation and pain in pediatric amputees. J Pain Symptom Manage. 1995; 10(1):21–29. [PubMed: 7714344] 9. Mercier C, Sirigu A. Training with virtual visual feedback to alleviate phantom limb pain. Neurorehabil Neural Repair. 2009; 23(6):587–594. [PubMed: 19171946] 10. Casale R, Damiani C, Rosati V. Mirror Therapy in the Rehabilitation of Lower-Limb Amputation Are There Any Contraindications? American Journal of Physical Medicine & Rehabilitation. 2009; 88(10):837–842. [PubMed: 21119317] 11. Ramachandran VS, Rogers-Ramachandran D, Cobb S. Touching the phantom limb. Nature. 1995; 377(6549):489–490. [PubMed: 7566144] 12. Thieme H, Morkisch N, Rietz C, Dohle C, Borgetto B. The Efficacy of Movement Representation Techniques for Treatment of Limb Pain-A Systematic Review and Meta-Analysis. J Pain. 2016; 17(2):167–180. [PubMed: 26552501] 13. Ezendam D, Bongers RM, Jannink MJ. Systematic review of the effectiveness of mirror therapy in upper extremity function. Disabil Rehabil. 2009; 31(26):2135–2149. [PubMed: 19903124] 14. Rothgangel AS, Braun SM, Beurskens AJ, Seitz RJ, Wade DT. The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature. Int J Rehabil Res. 2011; 34(1):1–13. [PubMed: 21326041] 15. Sumitani M, Miyauchi S, McCabe CS, et al. Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report. Rheumatology (Oxford). 2008; 47(7):1038–1043. [PubMed: 18463143] 16. Eastern Metropolitan Region Palliative Care Consortium. 2013 17. Schechter, N., Berde, C., Yaster, M. Pain in infants, children, and adolescents. Baltimore, Maryland: 1993. 18. Gregory, G. Pediatric Anesthesia. 3. New York: Churchill Livingstone; 1994. 19. Benzon, H., Raja, S., Liu, S., Fishman, S., Cohn, S. Essentials of pain medicine. 3. Philadelphia, PA: Elsevier Saunders; 2011.
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Mirror Therapy Study Flowchart (n=21) Footnotes and Abbreviations PLP, phantom limb pain MT, mirror therapy * One patient’s data did not contribute to the duration of PLP and duration of follow up because of still receiving treatment for PLP, including MT, at the closing date for data collection for the study. ** One patient’s data did not contribute to any pain outcomes (i.e., pain scores, pain medications, duration of PLP or duration of follow up) because the clinical scenario was that of an amputation 2 weeks after a limb-sparing operation, followed by another surgical
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procedure during the course of the study, which confounded the post-amputation painoutcome measures. *** One patient’s data did not contribute to the duration of PLP and duration of follow up due to being lost to follow-up at 4 weeks due to transfer to another institution.
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Figure 2.
Duration of Phantom Limb Pain (days), in the Mirror Therapy Group and Non-Mirror Therapy Group (p=0.08) Footnotes and Abbreviations MT, mirror therapy group Non-MT, non-mirror therapy group
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Table 1
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Morphine Equivalent Dose (MED) Conversions14–17 Route of Administration
MED (IV)
Hydromorphone (Dilaudid)
IV
×5
Hydromorphone (Dilaudid)
PO
× 0.6
Oxycodone
PO
× 0.5
Methadone
PO
÷2
Methadone
IV
×1
Codeine
PO
÷ 12
Hydrocodone (Lortab)
PO
÷3
Drug (Brand name)
Morphine
PO, SR
÷3
Fentanyl
IV
× 100
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Abbreviations: IV, intravenous; PO, by mouth; SR, slow-release formulation
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Table 2
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Demographic Data, Diagnoses and Types of Surgery for Adolescent and Young Adult Patients with Phantom Limb Pain (n=18) Total Cohort
MT Group
Non-MT Group
n (%)
n (%)
n (%)
18 (100)
9 (50)
9 (50)
13 (8–24)
12 (8–20)
16 (10–24)
Male
15 (83.3)
8 (88.9)
7 (77.8)
Female
3 (16.7)
1 (11.1)
2 (22.2)
White
12 (66.7)
6 (66.7)
6 (66.7)
Black
5 (27.8)
2 (22.2)
3 (33.3)
Other
1 (5.5)
1 (11.1)
0 (0)
Ewing sarcoma
2 (11.1)
1 (11.1)
1 (11.1)
Osteosarcoma
12 (66.7)
7 (77.8)
5 (55.6)
Synovial sarcoma
3 (16.7)
0 (0)
3 (33.3)
1 (5.5)
1 (11.1)
0 (0)
AKA
13 (72.2)
7 (77.8)
6 (66.7)
BKA
2 (11)
0 (0)
2 (22.2)
BEA
1 (5.6)
0 (0)
1 (11.1)
Hemipelvectomy
1(5.6)
1 (11.1)
0 (0)
Forequarter
1(5.6)
1 (11.1)
0 (0)
Characteristic
No. of Patients Age (years)
Median (range) Sex
Race
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Primary Diagnosis
Undifferentiated sarcoma Type of Amputation
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Abbreviations: AKA, above-knee amputation; BEA, below-elbow amputation; BKA, below-knee amputation; MT, mirror therapy
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Table 3
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Incidence and Duration of Phantom Limb Pain and Duration of Follow-up by the Pain Service PLP Incidence and Duration Overall incidence (%)
Incidence at 1 year post-amputation (%)
Duration of PLP1
Duration of follow-up by pain service1
18/21 (85.7)
Group Total
7/18 (38.9)
403 (± 326)
81 (± 42)
MT
1/9 (11.1)
246 (± 200)
84 (± 46)
Non-MT
6/9 (66.7)
541 (± 363)
77 (± 37)
1
Durations are noted as the mean number of days (± SD).
Abbreviations: MT, mirror therapy; PLP, phantom limb pain
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Table 4
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Pain Scores in Adolescent and Young Adult Patients with Phantom Limb Pain
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Time
MT Group n, Median (range)
Non – MT Group n, Median (range)
Week 1
*8, 2.93 (0.45, 4.07)
9, 2.45 (0.86, 5.60)
Week 2
8, 2.92 (0.67, 4.40)
9, 1.75 (0.00, 5.44)
Week 3
7, 3.00 (0.00, 4.00)
8, 2.55 (0.50,5.00)
Week 4
8, 2.38 (0.00, 4.60)
7, 2.00 (0.00,5.50)
Week 8
8, 0.00 (0.00, 4.50)
6, 0.34 (0.00,2.40)
Week 12
7, 0.00 (0.00, 2.33)
5, 0.00 (0.00,3.67)
Week 16
8, 0.00 (0.00, 4.00)
6, 0.00 (0.00,1.00)
Week 20
5, 0.00 (0.00, 3.00)
2, 0.00 (0.00,0.00)
Week 24
4, 0.00 (0.00, 0.00)
2, 0.00 (0.00,0.00)
Abbreviations: MT, mirror therapy
*
One patient in the mirror therapy group – missing data for pain scores
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Rehabil Oncol. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: Rehabil Oncol. 2016 July ; 34(3): 104–110.
Mirror Therapy for Phantom Limb Pain at a Pediatric Oncology Institution Doralina L. Anghelescu, MD [Member], Department of Pediatric Medicine, Division of Anesthesiology, Director, Pain Management Service, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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Cassandra N. Kelly, BS [Pediatric Oncology Education Student], St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Brenda D. Steen, MNS [Clinical Research Associate], Department of Anesthesiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Jianrong Wu, PhD [Associate Member], Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Huiyun Wu, MS [Senior Biostatistician], Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Brian M. DeFeo, DPT, OCS [Physical Therapist], Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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Kristin Scobey, DPT, PCS [Director], and Rehabilitation Services, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA Laura Burgoyne, BM, BS [Senior Staff Specialist] Children’s Anaesthesia, Women’s and Children’s Hospital, North Adelaide SA 5006, Australia
Abstract Background and Purpose/Objective—Mirror therapy has not been reported for phantom limb pain (PLP) in pediatric oncology. Our aims are to describe the incidence and duration of PLP post-amputation, the duration of follow-up, pain scores and pain medications, and the differences between a group that received mirror therapy (MT) in addition to the standard treatment and a group that received only the standard treatment (non-MT).
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Methods—A retrospective review of patients’ medical records from June 2009 to March 2015 was completed. The demographic characteristics, diagnoses and types of surgery were collected. The incidence and duration of PLP, duration of pain service follow-up, pain medications and pain scores were collected and analyzed using the Wilcoxon rank sum test. Results—Of 21 patients who underwent amputations (median age 13 years, range, 8–24 years), most common primary diagnosis osteosarcoma), 18 (85.7%) experienced PLP; 38.9% of them
Corresponding Author: Doralina L. Anghelescu, MD, Division of Anesthesiology, MS 130, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA, Phone: 901-595-4032, FAX: 901-595-4061, [email protected]. Disclosures: The authors have no conflicts of interest to disclose.
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experienced PLP at 1 year post-amputation (11.1% of the MT group and 66.7% of the non-MT group). The MT group and non-MT groups experienced PLP for a mean (± SD) of 246 (± 200) days, and 541 (± 363) days, respectively (p=0.08). The mean (SD) opioid doses (mg/kg/day) in the MT and non-MT groups were 0.81 (± 0.99) and 0.33 (± 0.31), respectively; the mean (SD) gabapentin doses (mg/kg/day) were 40.1 (± 21) for the MT group and 30.5 (± 11.5) for the nonMT group. Conclusion—MT in children with cancer-related amputations is associated with lower incidence of PLP at 1 year and shorter duration of PLP. Keywords mirror therapy; phantom limb pain; pediatric oncology
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BACKGROUND Phantom Limb Pain in the General Population
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Phantom limb pain (PLP), the sensation of pain experienced in a limb that is no longer there, is a very common result of limb amputation.1 According to the literature, 60% to 90% of amputees experience PLP at some point in their lifetime.2 Phantom limb pain can occur whether the amputation is traumatic or surgical, and the incidence is generally higher after a traumatic loss or if there is a pre-existing painful condition, as opposed to a planned surgical amputation of a non-painful limb.3 Most commonly, PLP has an early onset; nevertheless, it can appear months or even years after the amputation. In 50% of patients who experience PLP, the symptoms develop immediately post-amputation, and in about 75%, PLP symptoms develop within 24 hours.4 Although the exact mechanism of PLP is still not fully understood, this phenomenon is widely thought to be related to conflicting input from motor, visual, sensory, and proprioceptive systems.5 It has been shown that there is an increased risk for PLP if the patient is female, has an upper extremity amputation, there is presence of pre-amputation pain, or if there is residual pain in the remaining limb.6 The incidence of PLP is thought to be lower in children than in adults, and PLP has not been reported in children younger than 4 years.1 Phantom Limb Pain in the Pediatric Oncology Population
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In a study of children and young adults (ages 6–27 years, of which 64% were younger than 18 years) with cancer-related surgical amputations, 64% suffered pre-amputation pain; 76% experienced PLP within the first year after amputation; and 10% experienced PLP at 1 year post-amputation.7 The study evaluated factors to predict PLP, and although all patients who experienced PLP 1 year after amputation were older than 18 years, had pre-amputation pain, and had a proximal limb amputation, none of these factors were statically significant, possibly due to the small sample size.7 Patients who undergo pediatric cancer–related amputations have a higher incidence of PLP (90%) than the pediatric amputation population as a whole (83%).8
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Mirror Therapy for Phantom Limb Pain
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A non-pharmacological intervention for PLP is mirror therapy (MT). After an amputation, an extensive reorganization of the sensorimotor cortex takes place, and the extent of cortical reorganization and the intensity of PLP are positively correlated.9 The aim of MT is to reverse the maladaptive reorganization within the sensorimotor cortex, thereby reducing PLP. MT consists of placing a mirror medial to the intact limb and allowing the patient to view a reflection of their anatomical limb in the visual space occupied by the phantom limb.10 Patients can move or touch their anatomical limb while looking into the mirror and visualizing both limbs doing the same action. MT is thought to provide the link between the visual and motor systems that is missing in PLP. MT was developed by Ramachandran and Rogers-Ramachandran in 1996; in their study, all of the subjects who received MT experienced a reduction in PLP.11
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Studies have shown variable success rates of MT for PLP12–14. Better effects were noted when MT was used to treat deep somatic pain, pressure, and proprioception than to treat superficial pain, and temperature sensitivity; this is due to the fact that deep tissues integrate sensorimotor nerves and create movements, while superficial tissues do not.15 MT has been integrated into the treatment of amputees, especially when other treatments such as pain medication, nerve blocks, physical therapy, and local anesthetics have been unsuccessful. Several factors have been evaluated for predictive value of success with MT, including preamputation pain, time between the amputation and beginning of MT, presence of telescoping sensation, distal vs. proximal amputations, and upper-vs. lower-extremity amputations.1,2
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Furthermore, although MT has been used for the past 2 decades in adults, no firm conclusion can be drawn regarding its effects for PLP in adults,12,14 furthermore, its efficacy has yet to be evaluated in children, adolescents, and young adults. The goal of this retrospective study was to describe the differences between pediatric patients who received MT in addition to the standard therapy for PLP (MT group) and those who received only the standard therapy (non-MT group) at our institution. The following outcome measures were assessed: duration of PLP, intensity of PLP, pain medications used and their dose regimens.
METHODS Patients and Medical Records Review
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This retrospective study included all patients who underwent an amputation at a pediatric oncology institution between June 2009 and March 2015, identified from the institution’s surgical database, including ages up to 24 years (children, adolescent and young adult) and all diagnoses. This study was approved by the Institutional Review Board. The information obtained from the medical records included demographic data, pain medication data, and pain score data. The demographic data collected included date of birth, age at the time of amputation, sex, race, and weight. Primary diagnosis, surgical procedure, date of surgical procedure, number of days of follow-up by the pain service, number of days with PLP, and date of MT initiation and/or number of sessions, if applicable, were also collected from the patients’ medical records. Time points for data collection for pain scores and pain medications included: postoperative days (PODs) 1 through 6, weeks 2 to 4, and Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
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months 2 to 6, or until the PLP resolved and/or the patient was discharged from the pain service, whichever occurred last. The daily data for PODs 1 through 6 were analyzed as one data point for Week 1. Medical records were also examined to determine if nonpharmacological interventions for pain were provided by the Psychology Service. Pain Scores Review
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During the chart review process, data collection regarding pain scores pertained to the diagnosis of PLP, while other sources and types of pain (i.e., stump pain, post-operative pain or localized neuroma after amputation) were excluded from the data collection. Specifically, the diagnosis of PLP was present if pain was described in the absent amputated extremity; perception of non-painful sensations in the absent extremity did not constitute PLP. A standard 11 point Numerical Pain Score (0–10) was used to assess pain throughout hospitalization and at outpatient visits. Pain scores were collected from the pain service notes, physical therapy notes, and nursing notes daily during hospitalization and on days of pain clinic visits in the outpatient setting. Mirror Therapy Data Review
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Patients were referred to physical therapy at the discretion of the referring surgeon with the specific indication to evaluate for MT and train in the use of MT as indicated. The time of the first MT session was dependent upon patient’s first reported symptoms of PLP, either at the initial evaluation or at follow up treatment sessions. During the initial physical therapy consult, symptoms were assessed, including PLP. Patients who reported PLP were provided with MT by a licensed physical therapist. The MT session consisted of placing the patient’s residual limb in a mirror box triangle with instructions to perform simple exercises such as ankle pumps, ankle circles, and quadriceps contractions while viewing both the intact extremity and its mirror reflection. The patients were encouraged to perform exercises bilaterally, imagining two intact extremities with visual feedback provided by the mirror box. Upon completion of initial MT session, patients were provided the mirror box and were advised to perform MT as needed as a home exercise program; patients were also scheduled for physical therapy follow up treatment sessions. At each follow up session, the history of PLP, the use of MT per home exercise program, and any changes in PLP following MT were reviewed. Patients were asked to report any PLP during the session, followed by therapistled MT if indicated. Patients that denied any recent symptoms of PLP received no further MT. The duration of MT sessions was individually based; patients were allowed to stop upon relief of pain or upon tiring of activity, usually following some decrease in pain. The frequency of MT sessions was dependent upon the frequency PLP episodes. Patients were advised to perform MT with every occurrence of PLP, up to several times per day, until experiencing no further symptoms. Pain Medication Data Review The pain medication data collected included doses and duration of treatment for opioids (including use of patient-controlled analgesia), gabapentin, amitriptyline, methadone, continuous peripheral nerve blocks, and epidural infusions. The medication administration record was the source for pain medications given while the patient was hospitalized, and the pain service notes provided additional pain medication data during the inpatient course and Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
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follow-up outpatient visits. The amount of “as needed” (PRN) medications used for pain was determined based on the pain diary or pain medication inventory from each pain service outpatient visit. The pain diaries provided direct data regarding the dose regimen and number of doses taken daily for pain. The pain medication inventory provided data on the number of remaining doses available and the number of doses prescribed for each pain medication during pain service outpatient visits. Equianalgesic conversion rates were used to convert opioid medications into intravenous (IV) morphine equivalent doses (MEDs), as milligram per kilogram per day (Table 1). The patient’s weight noted for dose calculations was the first available weight after amputation, and this value was used throughout the duration of the data collection. Statistical Analysis
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Pain scores, pain medication data, duration of NP medication use, duration of NP, and duration of continuous epidural and nerve-block infusions were analyzed and reported as descriptive statistics: mean (± SD) and median (range), in the MT group and non-MT group. The Wilcoxon rank sum test was used to examine the difference in distribution of durations, dose, and pain score between MT group and non-MT group. Multiple comparisons over different time points were adjusted for using the False Discovery Rate (FDR) method. All tests were 2-sided and the significance level was set at 0.05. All the computations were done using SAS software version 9.3 (SAS Institute Inc., Cary, NC, USA).
RESULTS Patient Characteristics
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Between June 2009 and March 2015, 21 patients under age 24 years underwent 21 amputations at our institution; 18 of them (85.7%) experienced PLP. The study outcomes presented here pertain to the 18 patients who developed PLP. Of the 18 patients with PLP, 9 received MT and 9 did not. The following number of patients contributed to each pain outcome analyzed, as described in the flow diagram (Figure 1): 1) incidence of PLP (n=18), 2) pain scores for PLP and pain medications (n=17), 3) duration of PLP and duration of follow up (n=15). As noted in the flow diagram (Figure 1), 1 patient was lost for follow up due to transfer to another institution at 4 weeks postoperatively; therefore, his data did not contribute to the duration of PLP or duration of follow-up by the pain service. This patient had not received MT interventions for PLP by the time of transfer. One patient in the MT group was still receiving treatment for PLP at the closing date for data collection for the study; therefore, his data did not contribute to the duration of PLP or duration of follow-up by the pain service. One patient in the MT group was excluded from analysis for all pain outcomes (i.e, pain medications, pain scores, duration of PLP and duration of follow up) because the clinical scenario was that of an amputation 2 weeks after a limb-sparing operation, followed by another surgical procedure during the course of the study, which confounded the post-amputation pain-outcome measures; his data contributed to the incidence and the demographic analysis. The median age of the patients was 13 years (range, 8–24 years), and the most common primary diagnosis was osteosarcoma. The demographic data and patient characteristics,
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including diagnoses and types of surgical amputations, for the entire cohort and the MT and non-MT groups are presented in Table 2. In this cohort, 18 (85.7%) experienced PLP; overall, 7 of 18 patients (38.9%) still had unresolved PLP at 1 year post-amputation, with a higher incidence of PLP in the non-MT group: 6 of 9 patients in the non-MT group (66.7%) vs. 1 of 9 patients in the MT group (11.1%). Mirror Therapy In 9 patients who received MT, the timing of therapy initiation varied; according to the physical therapists’ notes, MT was initiated when PLP started and was prescribed “as needed” for PLP. Proper techniques were taught at the beginning of physical therapy, and patients were instructed to continue the MT at home, whenever the PLP was bothersome. Seven patients with complete MT data received an average of 4 MT sessions with the physical therapists and an unknown number of sessions at home.
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Duration of Phantom Limb Pain and Follow-up by the Pain Service Patients in the non-MT group experienced a longer duration of PLP than the patients in the MT group. The mean duration of PLP was 246 days (± 200 days) for the MT group and 541 days (± 363 days) for the non-MT group (p=0.08), respectively (Figure 2 and Table 3). The MT and non-MT groups had a mean duration of follow up by the pain service of 84 days (± 46 days) and 77 days (± 37 days), respectively (p=0.77) (Table 3). The PLP eventually resolved in all study subjects. Pain Medications
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The mean opioid doses expressed as MED in the MT and non-MT groups for the overall duration of treatment were 0.81 mg/kg per day (± 0.99 mg/kg per day) and 0.33 mg/kg per day (± 0.31 mg/kg per day), respectively. Although the MT group received higher doses at all data points in time, none of the differences reached statistical significance. The mean gabapentin doses for the overall duration of treatment were 40.1 mg/kg per day (± 21 mg/kg per day) for the MT group and 30.5 mg/kg per day (± 11.5 mg/kg per day) for the non-MT group. We found no significant differences in gabapentin doses at any data points. Amitriptyline and methadone doses were not statistically analyzed because of the insufficient amount of data. Nine of the 17 patients with PLP were treated with amitriptyline (6 in the MT group and 3 in the non-MT group), and 5 received methadone treatment (4 in the MT group and 1 in the non-MT group).
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Continuous nerve blocks or epidural infusions were administered for a mean of 5.1 days (± 4.7 days) for the entire cohort, 5.1 days (± 2.9 days) for the non-MT group, and 5 days (± 6 days) for the MT group. All patients, except one in the MT group, received nonpharmacologic interventions for pain from a clinical psychologist. For most patients, the psychology consultation was provided before the amputation and continued post-amputation for several sessions.
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Pain Scores
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The differences between the pain scores in the MT group and non-MT group were not significant at any data point (adjusted p-value = 1.0) (Table 4).
DISCUSSION This is the first report on the use of MT for PLP in children, adolescents, and young adults post-amputation and specifically to investigate the differences in incidence and duration of PLP, duration of follow-up by the pain service, pain medication doses and pain scores.
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The main differences between the MT and non-MT groups were a longer duration of PLP and a higher incidence of PLP in the non-MT group at 1 year post-amputation. The non-MT group had PLP for more than twice as long as the MT group, and the incidence of PLP in the non-MT group at 1 year was 66.7%% vs. 11.1% in MT group. MT did not appear to be associated with a reduction in the use of medications, either opioid or neuropathic pain– specific medications (gabapentin, amitriptyline, and methadone) or lower pain score. A possible explanation for these findings is selection bias, as patients who experienced more severe PLP may have been more likely to be directed to have physical therapy evaluation and treatment with MT. The patients with more severe pain may have “self-selected” to receive MT in addition to the standard pharmacologic and non-pharmacologic therapies; these patients also received higher doses of opioid and gabapentin, which is suggestive of clinical scenarios of more difficult to control pain. Additionally, the MT group included 2 cases of proximal amputations (a forequarter amputation and an external hemipelvectomy), which are more likely to be associated with increased severity and duration of PLP.
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The overall incidence of PLP we report here is within the range of PLP incidence reported by other pediatric studies. Eighteen of 21 (85.7%) patients experienced PLP within the first year following their amputations, and 38.9% of those patients had persistent PLP at 1 year post-amputation. Our findings are consistent with those of the study by Krane et al. which found that over a 10-year period, 90% of pediatric cancer–related amputations resulted in PLP8, and they are slightly higher than the findings of the study by Burgoyne et al., which reported that 76% of patients had PLP, and only 10% experienced PLP that persisted at 1 year post-amputation.7
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Due to the retrospective design of this study and the fact that each patient had many concurrent interventions for pain, our findings do not conclusively indicate that MT contributed to the difference in incidence of PLP at 1 year or duration of PLP. Furthermore, the use of higher doses of opioids and gabapentin in the MT group is suggestive of more severe pain in this group. A limitation of our study is the specific modality of delivering MT. The literature reporting MT outcomes describes the use of prescribed MT on a scheduled basis, such as sessions of 30 min/day, 5 days/week, for 3 weeks.10 This is seemingly most effective for reversing the maladaptive cortical reorganization that occurs after an amputation. The use of MT “as needed,” rather than on a scheduled basis, may have been less effective in reducing the duration and intensity of the PLP. It is reasonable to hypothesize that in order to be effective,
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MT should be done consistently. Another limitation of our MT data is the lack of documentation on the frequency and duration of MT regimens continued at home. The actual use of MT at home is not known and may have been inconsistent, as there was no assurance of compliance. Currently, the literature is conflicting as to whether the timing of MT initiation is a crucial factor in its success. The fact that MT initiation dates were variable in our study group affects the strength of the outcome data.
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One must also be cognizant of the dissimilarity between the clinical characteristics of the 2 groups: the MT group included 7 above-knee amputation (AKA) cases, 1 hemipelvectomy, and 1 forequarter amputation, and the non-MT group included 6 AKA cases, 2 below-knee amputations (BKA), and 1 below-elbow amputation (BEA). Proximal amputations are associated more frequently with PLP than are distal amputations.1 By their nature, the hemipelvectomy and the forequarter amputation are much more painful procedures with more difficult recovery periods. Patients who undergo those surgeries are expected to require higher consumption of pain medications than are those who undergo more distal amputations. This dissimilarity may have contributed to the higher pain medication consumption in the MT group. Another difference was that the median age of the MT group (12 years) was younger than that of non-MT group (16 years), which also could have influenced the results.
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Patients in the MT group received higher doses of opioids and gabapentin than did those in the non-MT group, from the beginning of the study period, even before MT interventions were initiated. The dose regimens of those medications may be associated with the severity of both nociceptive postoperative pain and PLP. These findings suggest that the patients in the MT group experienced more severe nociceptive postoperative pain and PLP than did the patients in the non-MT group, despite the lack of disparity in pain scores. Of note, the use amitriptyline, and methadone post-amputation, in addition to opioids and gabapentin, usually reflects a need to address the symptoms of PLP by adding second (tricyclic antidepressant) and third line (methadone) therapies for PLP; while the consumption of opioids cannot be attributed with certainty to the need to treat PLP (neuropathic pain) vs. nociceptive postoperative pain, during the immediate-postoperative period. In conclusion, the MT group did experience a shorter duration of PLP and lower incidence of PLP at 1 year, when compared to the non-MT group. The findings of this study highlight the need for prospective, randomized studies of MT vs. non-MT groups of pediatric, adolescent and young adult patients with PLP.
Acknowledgments Author Manuscript
Funding: This study was supported in part by the National Cancer Institute Cancer Center Support Core Grant 5P30CA-21765-32, National Cancer Institute Grant 5R25CA23944, and ALSAC, neither of which had a role in its planning, conduct, analysis, or reporting.
REFERENCES 1. Pirowska A, Wloch T, Nowobilski R, Plaszewski M, Hocini A, Menager D. Phantom phenomena and body scheme after limb amputation: A literature review. Neurol Neurochir Pol. 2014; 48(1):52– 59. [PubMed: 24636771]
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2. Foell J, Bekrater-Bodmann R, Diers M, Flor H. Mirror therapy for phantom limb pain: brain changes and the role of body representation. Eur J Pain. 2014; 18(5):729–739. [PubMed: 24327313] 3. Hanling SR, Wallace SC, Hollenbeck KJ, Belnap BD, Tulis MR. Preamputation Mirror Therapy May Prevent Development of Phantom Limb Pain: A Case Series. Anesth Analg. 2010; 110(2):611– 614. [PubMed: 19917622] 4. Kim SY, Kim YY. Mirror Therapy for Phantom Limb Pain. Korean J Pain. 2012; 25(4):272–274. [PubMed: 23091690] 5. Schmalzl L, Ragno C, Ehrsson HH. An alternative to traditional mirror therapy: illusory touch can reduce phantom pain when illusory movement does not. Clin J Pain. 2013; 29(10):e10–e18. [PubMed: 23446074] 6. Subedi B, Grossberg G. Phantom Limb Pain: Mechanisms and Treatment Approaches. Pain Res Treat. 2011; 2011:1–8. 7. Burgoyne LL, Billups CA, Jiron JL Jr, et al. Phantom limb pain in young cancer-related amputees: recent experience at St Jude children's research hospital. Clin J Pain. 2012; 28(3):222–225. [PubMed: 21785344] 8. Krane EJ, Heller LB. The prevalence of phantom sensation and pain in pediatric amputees. J Pain Symptom Manage. 1995; 10(1):21–29. [PubMed: 7714344] 9. Mercier C, Sirigu A. Training with virtual visual feedback to alleviate phantom limb pain. Neurorehabil Neural Repair. 2009; 23(6):587–594. [PubMed: 19171946] 10. Casale R, Damiani C, Rosati V. Mirror Therapy in the Rehabilitation of Lower-Limb Amputation Are There Any Contraindications? American Journal of Physical Medicine & Rehabilitation. 2009; 88(10):837–842. [PubMed: 21119317] 11. Ramachandran VS, Rogers-Ramachandran D, Cobb S. Touching the phantom limb. Nature. 1995; 377(6549):489–490. [PubMed: 7566144] 12. Thieme H, Morkisch N, Rietz C, Dohle C, Borgetto B. The Efficacy of Movement Representation Techniques for Treatment of Limb Pain-A Systematic Review and Meta-Analysis. J Pain. 2016; 17(2):167–180. [PubMed: 26552501] 13. Ezendam D, Bongers RM, Jannink MJ. Systematic review of the effectiveness of mirror therapy in upper extremity function. Disabil Rehabil. 2009; 31(26):2135–2149. [PubMed: 19903124] 14. Rothgangel AS, Braun SM, Beurskens AJ, Seitz RJ, Wade DT. The clinical aspects of mirror therapy in rehabilitation: a systematic review of the literature. Int J Rehabil Res. 2011; 34(1):1–13. [PubMed: 21326041] 15. Sumitani M, Miyauchi S, McCabe CS, et al. Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report. Rheumatology (Oxford). 2008; 47(7):1038–1043. [PubMed: 18463143] 16. Eastern Metropolitan Region Palliative Care Consortium. 2013 17. Schechter, N., Berde, C., Yaster, M. Pain in infants, children, and adolescents. Baltimore, Maryland: 1993. 18. Gregory, G. Pediatric Anesthesia. 3. New York: Churchill Livingstone; 1994. 19. Benzon, H., Raja, S., Liu, S., Fishman, S., Cohn, S. Essentials of pain medicine. 3. Philadelphia, PA: Elsevier Saunders; 2011.
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Mirror Therapy Study Flowchart (n=21) Footnotes and Abbreviations PLP, phantom limb pain MT, mirror therapy * One patient’s data did not contribute to the duration of PLP and duration of follow up because of still receiving treatment for PLP, including MT, at the closing date for data collection for the study. ** One patient’s data did not contribute to any pain outcomes (i.e., pain scores, pain medications, duration of PLP or duration of follow up) because the clinical scenario was that of an amputation 2 weeks after a limb-sparing operation, followed by another surgical
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procedure during the course of the study, which confounded the post-amputation painoutcome measures. *** One patient’s data did not contribute to the duration of PLP and duration of follow up due to being lost to follow-up at 4 weeks due to transfer to another institution.
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Figure 2.
Duration of Phantom Limb Pain (days), in the Mirror Therapy Group and Non-Mirror Therapy Group (p=0.08) Footnotes and Abbreviations MT, mirror therapy group Non-MT, non-mirror therapy group
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Table 1
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Morphine Equivalent Dose (MED) Conversions14–17 Route of Administration
MED (IV)
Hydromorphone (Dilaudid)
IV
×5
Hydromorphone (Dilaudid)
PO
× 0.6
Oxycodone
PO
× 0.5
Methadone
PO
÷2
Methadone
IV
×1
Codeine
PO
÷ 12
Hydrocodone (Lortab)
PO
÷3
Drug (Brand name)
Morphine
PO, SR
÷3
Fentanyl
IV
× 100
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Abbreviations: IV, intravenous; PO, by mouth; SR, slow-release formulation
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Table 2
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Demographic Data, Diagnoses and Types of Surgery for Adolescent and Young Adult Patients with Phantom Limb Pain (n=18) Total Cohort
MT Group
Non-MT Group
n (%)
n (%)
n (%)
18 (100)
9 (50)
9 (50)
13 (8–24)
12 (8–20)
16 (10–24)
Male
15 (83.3)
8 (88.9)
7 (77.8)
Female
3 (16.7)
1 (11.1)
2 (22.2)
White
12 (66.7)
6 (66.7)
6 (66.7)
Black
5 (27.8)
2 (22.2)
3 (33.3)
Other
1 (5.5)
1 (11.1)
0 (0)
Ewing sarcoma
2 (11.1)
1 (11.1)
1 (11.1)
Osteosarcoma
12 (66.7)
7 (77.8)
5 (55.6)
Synovial sarcoma
3 (16.7)
0 (0)
3 (33.3)
1 (5.5)
1 (11.1)
0 (0)
AKA
13 (72.2)
7 (77.8)
6 (66.7)
BKA
2 (11)
0 (0)
2 (22.2)
BEA
1 (5.6)
0 (0)
1 (11.1)
Hemipelvectomy
1(5.6)
1 (11.1)
0 (0)
Forequarter
1(5.6)
1 (11.1)
0 (0)
Characteristic
No. of Patients Age (years)
Median (range) Sex
Race
Author Manuscript
Primary Diagnosis
Undifferentiated sarcoma Type of Amputation
Author Manuscript
Abbreviations: AKA, above-knee amputation; BEA, below-elbow amputation; BKA, below-knee amputation; MT, mirror therapy
Author Manuscript Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
Anghelescu et al.
Page 15
Table 3
Author Manuscript
Incidence and Duration of Phantom Limb Pain and Duration of Follow-up by the Pain Service PLP Incidence and Duration Overall incidence (%)
Incidence at 1 year post-amputation (%)
Duration of PLP1
Duration of follow-up by pain service1
18/21 (85.7)
Group Total
7/18 (38.9)
403 (± 326)
81 (± 42)
MT
1/9 (11.1)
246 (± 200)
84 (± 46)
Non-MT
6/9 (66.7)
541 (± 363)
77 (± 37)
1
Durations are noted as the mean number of days (± SD).
Abbreviations: MT, mirror therapy; PLP, phantom limb pain
Author Manuscript Author Manuscript Author Manuscript Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
Anghelescu et al.
Page 16
Table 4
Author Manuscript
Pain Scores in Adolescent and Young Adult Patients with Phantom Limb Pain
Author Manuscript
Time
MT Group n, Median (range)
Non – MT Group n, Median (range)
Week 1
*8, 2.93 (0.45, 4.07)
9, 2.45 (0.86, 5.60)
Week 2
8, 2.92 (0.67, 4.40)
9, 1.75 (0.00, 5.44)
Week 3
7, 3.00 (0.00, 4.00)
8, 2.55 (0.50,5.00)
Week 4
8, 2.38 (0.00, 4.60)
7, 2.00 (0.00,5.50)
Week 8
8, 0.00 (0.00, 4.50)
6, 0.34 (0.00,2.40)
Week 12
7, 0.00 (0.00, 2.33)
5, 0.00 (0.00,3.67)
Week 16
8, 0.00 (0.00, 4.00)
6, 0.00 (0.00,1.00)
Week 20
5, 0.00 (0.00, 3.00)
2, 0.00 (0.00,0.00)
Week 24
4, 0.00 (0.00, 0.00)
2, 0.00 (0.00,0.00)
Abbreviations: MT, mirror therapy
*
One patient in the mirror therapy group – missing data for pain scores
Author Manuscript Author Manuscript Rehabil Oncol. Author manuscript; available in PMC 2017 July 01.
