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.

Effects of Combined and Alone Transcranial Motor Cortex Stimulation and Mirror Therapy in Phantom Limb Pain: A Randomized Factorial Trial.

Phantom limb pain (PLP) is a frequent complication in amputees, which is often refractory to treatments. We aim to assess in a factorial trial the effects of transcranial direct current stimulation (tDCS) and mirror therapy (MT) in patients with traumatic lower limb amputation; and whether the motor cortex plasticity changes drive these results. In this large randomized, blinded, 2-site, sham-controlled, 2 × 2 factorial trial, 112 participants with traumatic lower limb amputation were randomized into treatment groups. The interventions were active or covered MT for 4 weeks (20 sessions, 15 minutes each) combined with 2 weeks of either active or sham tDCS (10 sessions, 20 minutes each) applied to the contralateral primary motor cortex. The primary outcome was PLP changes on the visual analogue scale at the end of interventions (4 weeks). Motor cortex excitability and cortical mapping were assessed by transcranial magnetic stimulation (TMS). We found no interaction between tDCS and MT groups (F = 1.90, P = .13). In the adjusted models, there was a main effect of active tDCS compared to sham tDCS (beta coefficient = -0.99, P = .04) on phantom pain. The overall effect size was 1.19 (95% confidence interval: 0.90, 1.47). No changes in depression and anxiety were found. TDCS intervention was associated with increased intracortical inhibition (coefficient = 0.96, P = .02) and facilitation (coefficient = 2.03, P = .03) as well as a posterolateral shift of the center of gravity in the affected hemisphere. MT induced no motor cortex plasticity changes assessed by TMS. These findings indicate that transcranial motor cortex stimulation might be an affordable and beneficial PLP treatment modality.

Interdisciplinary Care for Amputees Network: A Novel Approach to the Management of Amputee Patient Populations.

Extremity amputation remains a common intervention for limb-threatening conditions. With advancement in surgical technique to address deleterious postoperative sequelae of limb removal, there is a salient need to develop and operationalize interdisciplinary care frameworks to provide more comprehensive care to an otherwise challenging patient population. Herein, we describe our interdisciplinary approach to the management of amputee patient populations at our institution, referred to as the Interdisciplinary Care for Amputees Network (ICAN). This novel framework focuses on 3 fundamental areas: combined preoperative patient evaluation, orthoplastic surgical intervention, and multi-specialty postoperative functional and psychosocial rehabilitation. Importantly, the successful implementation of a combined orthoplastic clinic requires establishing a working relationship among providers to leverage increased provider familiarity. This, coupled with sufficient clinic space, dedicated operating room time, and standardized patient workflow, serves to improve care and meet patient goals of pain minimization, return to desired functional status, and improvement in quality of life.

Symptom Clusters and Functional Impairment in Individuals Treated for Lyme Borreliosis.

Context: Persistent fatigue, pain, and neurocognitive impairment are common in individuals following treatment for Lyme borreliosis (LB). Poor sleep, depression, visual disturbance, and sensory neuropathies have also been reported. The cause of these symptoms is unclear, and widely accepted effective treatment strategies are lacking. Objectives: To identify symptom clusters in people with persistent symptoms previously treated for LB and to examine the relationship between symptom severity and perceived disability. Methods: This was a retrospective chart review of individuals with a history of treatment of LB referred to The Dean Center for Tick-Borne Illness at Spaulding Rehabilitation Hospital between 2015 and 2018 (n = 270) because of persistent symptoms. Symptoms and functional impairment were collected using the General Symptom Questionnaire-30 (GSQ-30), and the Sheehan Disability Scale. Clinical tests were conducted to evaluate for tick-borne co-infections and to rule out medical disorders that could mimic LB symptomatology. Exploratory factor analysis was performed to identify symptom clusters. Results: Five symptom clusters were identified. Each cluster was assigned a name to reflect the possible underlying etiology and was based on the majority of the symptoms in the cluster: the neuropathy symptom cluster, sleep-fatigue symptom cluster, migraine symptom cluster, cognitive symptom cluster, and mood symptom cluster. Symptom severity for each symptom cluster was positively associated with global functional impairment (p < 0.001). Conclusion: Identifying the interrelationship between symptoms in post-treatment LB in a cluster can aid in the identification of the etiological basis of these symptoms and could lead to more effective symptom management strategies. Key Message: This article describes symptom clusters in individuals with a history of Lyme borreliosis. Five clusters were identified: sleep-fatigue, neuropathy, migraine-like, cognition, and mood clusters. Identifying the interrelationship between symptoms in each of the identified clusters could aid in more effective symptom management through identifying triggering symptoms or an underlying etiology.

Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control.

Opioid consumption for those in comprehensive inpatient rehabilitation units is high because of the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes because of maladaptive behaviors and poor engagement during therapies. It is critical to developing evidence-based pharmacobehavioral interventions. Based on principles of classical conditioning, conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation, and this technique takes advantage of the possibility of association learning and opioid pharmacology to promote evoked placebo-driven analgesia. OBJECTIVES: In this brief report, we evaluate the feasibility of COLP as a pharmacobehavioral intervention to decrease total opioid consumption in patients with pain hospitalized at Spaulding Rehabilitation Hospital. METHODS: Inpatients with spinal cord injury and polytrauma (n = 20) with moderate to severe pain were randomized to receive COLP (n = 10) or treatment-as-usual for 6 consecutive days. Opioid utilization was measured by morphine equivalents using the morphine equivalent dose conversion; pain severity was assessed using the numerical visual analog scale. RESULTS: Conditioning open-label placebo significantly reduced total opioid consumption by the end of the intervention period (P ≤ 0.001). Pain reduction was also significant for the COLP group (P = 0.005), whereas the treatment-as-usual group demonstrated a trend towards pain reduction (P = 0.05). CONCLUSIONS: This study presents the first data in the use of a pharmacobehavioral intervention that capitalize on the benefits of open-label placebo and classical drug conditioning for opioid dose reduction in a population with moderate to severe pain exposed to intensive inpatient rehabilitation.

Real-time Video Projection in an MRI for Characterization of Neural Correlates Associated with Mirror Therapy for Phantom Limb Pain.

Mirror therapy (MT) has been proposed as an effective rehabilitative strategy to alleviate pain symptoms in amputees with phantom limb pain (PLP). However, establishing the neural correlates associated with MT therapy have been challenging given that it is difficult to administer the therapy effectively within a magnetic resonance imaging (MRI) scanner environment. To characterize the functional organization of cortical regions associated with this rehabilitative strategy, we have developed a combined behavioral and functional neuroimaging protocol that can be applied in participants with a leg amputation. This novel approach allows participants to undergo MT within the MRI scanner environment by viewing real-time video images captured by a camera. The images are viewed by the participant through a system of mirrors and a monitor that the participant views while lying on the scanner bed. In this manner, functional changes in cortical areas of interest (e.g., sensorimotor cortex) can be characterized in response to the direct application of MT.

STRATEGIES TO ENHANCE RECRUITMENT METHODS IN PHANTOM LIMB PAIN CLINICAL TRIALS.

Phantom Limp Pain (PLP) was first described in 1551. To date, its mechanisms and novel interventions remain mostly untested. Only limited conclusions can be drawn from few and small randomized clinical trials (RCTs) on PLP. In this scenario, recruitment strategies are crucial in order to overcome inherent challenges to recruit PLP subjects for clinical trials. Although there are many methods to enhance recruitment and also retention, in this article we discuss these methods based on a common topic: dissemination. We summarize and discuss 10 strategies of recruitment related to the dissemination of information based on the notion that an increase in trial awareness may lead to both increased recruitment and also increased external generalizability. In addition, in our discussion we included insights based on our experience recruiting PLP patients for our large NIH-sponsored clinical trial. Although specific regulatory considerations need to be considered when choosing the methods of recruitment, which may vary across different countries and Institutional Review Boards (IRBs), these strategies may be applicable to most of research settings.

Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol.

BACKGROUND: Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP. OBJECTIVE: The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees. METHODS: A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention. RESULTS: This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years. CONCLUSIONS: This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf).

The effect of social integration on outcomes after major lower extremity amputation.

OBJECTIVE: Major lower extremity (MLE) amputation is a common procedure that results in a profound change in a patient's life. We sought to determine the association between social support and outcomes after amputation. We hypothesized that patients with greater social support will have better post amputation outcomes. METHODS: From November 2011 to May 2013, we conducted a cross-sectional, observational, multicenter study. Social integration was measured by the social integration subset of the Short Form Craig Handicap Assessment and Reporting Technique. Systemic social support was assessed by comparing a United States and Tanzanian population. Walking function was measured using the 6-minute walk test and quality of life (QoL) was measured using the EuroQol-5D. RESULTS: We recruited 102 MLE amputees. Sixty-three patients were enrolled in the United States with a mean age of 58.0. Forty-two (67%) were male. Patients with low social integration were more likely to be unable to ambulate (no walk 39% vs slow walk 23% vs fast walk 10%; P = .01) and those with high social integration were more likely to be fast walkers (no walk 10% vs slow walk 59% vs fast walk 74%; P = .01). This relationship persisted in a multivariable analysis. Increasing social integration scores were also positively associated with increasing QoL scores in a multivariable analysis (ß, .002; standard error, 0.0008; P = .02). In comparing the United States population with the Tanzanian cohort (39 subjects), there were no differences between functional or QoL outcomes in the systemic social support analysis. CONCLUSIONS: In the United States population, increased social integration is associated with both improved function and QoL outcomes among MLE amputees. Systemic social support, as measured by comparing the United States population with a Tanzanian population, was not associated with improved function or QoL outcomes. In the United States, steps should be taken to identify and aid amputees with poor social integration.

High-resolution dynamic angiography using flat-panel volume CT: feasibility demonstration for neuro and lower limb vascular applications.

OBJECTIVE: This paper evaluates a prototype flat-panel volume CT (fpVCT) for dynamic in vivo imaging in a variety of neurovascular and lower limb applications. METHODS: Dynamic CTA was performed on 12 patients (neuro = 8, lower limb = 4) using an fpVCT with 120 kVp, 50 mA, rotation time varying from 8 to 19 s, and field of view of 25 × 25 × 18 cm(3). Four-dimensional data sets (i.e. 3D images over time) were reconstructed and reviewed. RESULTS: Dynamic CTA demonstrated sufficient spatio-temporal resolution to elucidate first-pass and recirculation dynamics of contrast bolus through neurovasclaur pathologies and phasic blood flow though lower-limb vasculature and grafts. The high spatial resolution of fpVCT resulted in reduced partial volume and metal beam-hardening artefacts. This facilitated assessment of vascular lumen in the presence of calcified plaque and evaluation of fractures, especially in the presence of fixation hardware. Evaluation of arteriovenous malformation using dynamic fpVCT angiography was of limited utility. CONCLUSIONS: Dynamic CTA using fpVCT can visualize time-varying phenomena in neuro and lower limb vascular applications and has suffcient diagnostic imaging quality to evaluate a number of pathologies affecting these regions. KEY POINTS: • CTA using fpVCT has sufficient spatial and temporal resolution to study phasic blood flow. • CTA using fpVCT reveals recurrence of aneurysms even after clipping/coiling. • fpVCT has reduced partial volume and metal beam-hardening artefacts. • fpVCT can show vessel lumen in the presence of calcified plaque. • CTA using fpVCT can demonstrate vascular supply to transplanted grafts.

A systematic review of functional and quality of life assessment after major lower extremity amputation.

BACKGROUND: When judging the success or failure of major lower extremity (MLE) amputation, the assessment of appropriate functional and quality of life (QOL) outcomes is paramount. The heterogeneity of the scales and tests in the current literature is confusing and makes it difficult to compare results. We provide a primer for outcome assessment after amputation and assess the need for the additional development of novel instruments. METHODS: MEDLINE, EMBASE, and Google Scholar were searched for all studies using functional and QOL instruments after MLE amputation. Assessment instruments were divided into functional and QOL categories. Within each category, they were subdivided into global and amputation-specific instruments. An overall assessment of instrument quality was obtained. RESULTS: The initial search revealed 746 potential studies. After a review of abstracts, 102 were selected for full review, and 40 studies were then included in this review. From the studies, 21 different assessment instruments were used 63 times. There were 14 (67%) functional measures and 7 (33%) QOL measures identified. Five (36%) of the functional instruments and 3 (43%) of the QOL measures were specific for MLE amputees. Sixteen instruments were used >1 time, but only 5 instruments were used >3 times. An additional 5 instruments were included that were deemed important by expert opinion. The 26 assessment instruments were rated. Fourteen of the best-rated instruments were then described. CONCLUSIONS: The heterogeneity of instruments used to measure both functional and QOL outcomes make it difficult to compare MLE amputation outcome studies. Future researchers should seek to use high-quality instruments. Clinical and research societies should endorse the best validated instruments for future use in order to strengthen overall research in the field.

Consensus statements regarding the multidisciplinary care of limb amputation patients in disasters or humanitarian emergencies: report of the 2011 Humanitarian Action Summit Surgical Working Group on amputations following disasters or conflict.

Limb amputations are frequently performed as a result of trauma inflicted during conflict or disasters. As demonstrated during the 2010 earthquake in Haiti, coordinating care of these patients in austere settings is complex. During the 2011 Humanitarian Action Summit, consensus statements were developed for international organizations providing care to limb amputation patients during disasters or humanitarian emergencies. Expanded planning is needed for a multidisciplinary surgical care team, inclusive of surgeons, anesthesiologists, rehabilitation specialists and mental health professionals. Surgical providers should approach amputation using an operative technique that optimizes limb length and prosthetic fitting. Appropriate anesthesia care involves both peri-operative and long-term pain control. Rehabilitation specialists must be involved early in treatment, ideally before amputation, and should educate the surgical team in prosthetic considerations. Mental health specialists must be included to help the patient with community reintegration. A key step in developing local health systems the establishment of surgical outcomes monitoring. Such monitoring can optimizepatient follow-up and foster professional accountability for the treatment of amputation patients in disaster settings and humanitarian emergencies.

Best practice guidelines on surgical response in disasters and humanitarian emergencies: report of the 2011 Humanitarian Action Summit Working Group on Surgical Issues within the Humanitarian Space.

The provision of surgery within humanitarian crises is complex, requiring coordination and cooperation among all stakeholders. During the 2011 Humanitarian Action Summit best practice guidelines were proposed to provide greater accountability and standardization in surgical humanitarian relief efforts. Surgical humanitarian relief planning should occur early and include team selection and preparation, appropriate disaster-specific anticipatory planning, needs assessment, and an awareness of local resources and limitations of cross-cultural project management. Accurate medical record keeping and timely follow-up is important for a transient surgical population. Integration with local health systems is essential and will help facilitate longer term surgical health system strengthening.

Pharmacokinetics of extended-release dipyridamole following administration through a gastrostomy tube: an open-label, case-control, two-centre study.

BACKGROUND: Many stroke survivors have severe dysphagia and are unable to take antithrombotic medications orally. OBJECTIVE: To evaluate whether dipyridamole concentrations achieved in the plasma of patients taking an extended-release formulation of the medication through a gastrostomy tube (G-tube) are therapeutic and similar to those achieved in the plasma of patients who receive the drug orally. METHODS: This was an open-label, case-control, two-centre study conducted in two academic centres in a metropolitan area. Patients included were those admitted following an acute cerebral infarction, with an indication for antiplatelet therapy for secondary prevention. Twelve patients with severe dysphagia requiring G-tube placement were cases, and 12 patients who were able to swallow safely served as controls. The components of Aggrenox (extended-release dipyridamole/aspirin [acetylsalicylic acid]), suspended in water, were administered twice daily for 5 days through the G-tube. The 12 control patients without dysphagia took the medication orally. Dipyridamole plasma concentrations were compared between the groups at three different timepoints on the fifth day: 2, 6 and 12 hours after administration. The main outcome measure was dipyridamole plasma concentrations on day 5 at all three timepoints. RESULTS: No significant difference in dipyridamole plasma concentrations between the groups was found at 2 hours (p = 0.18), 6 hours (p = 0.92) or 12 hours (p = 0.69). CONCLUSION: Dipyridamole plasma concentrations obtained following administration of extended-release dipyridamole through a G-tube in dysphagic patients achieved similar therapeutic levels to those obtained in patients taking the medication orally.