Faculty Bibliography

The Revolutionizing Prosthetics 2009 program conducted by the Defense Advanced Research Projects Agency (DARPA) has resulted in a Virtual Integration Environment (VIE) that provides a common development platform for researchers and clinicians that design, model and build prosthetic limbs and then integrate and test them with patients. One clinical need that arose during the VIE development was a feature to easily create and model animations that represent patient activities of daily living (ADLs) and simultaneously capture real-time surface EMG activity from the residual limb corresponding to the ADLs. An application of this feature is being made by the Walter Reed Military Amputee Research Program (MARP) where they are utilizing the VIE to investigate methods of reducing upper extremity amputee phantom limb pain (PLP).

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Phantom limb phenomena are well characterized, but the underlying mechanisms remain unclear. Here we report a patient who relieves his phantom sensations and pain, experienced as itching and cramping, through scratching or massaging his prosthesis or the leg of another person. This pain relief occurs only when phantom limb sensations are present. We hypothesize that symptom relief results from incorporation of the foreign limb into the patient's body image, mediated by the sensory mirror neuron system, relieving pain by restoring concordance between sensory systems.

Traumatic brain injury (TBI) is a prevalent condition throughout the civilian and military populations. Although TBI can be classified as mild, moderate, or severe, most TBIs are considered mild. Understanding the pathophysiologic mechanism(s) of mild TBI through basic science and clinical cohort studies is an area of active research. While it is well understood that most people recover from a mild TBI with minimal treatment, some patients experience long-term consequences that require rehabilitation and specialized care. Common characteristics of brain injury include loss of consciousness (LOC), posttraumatic amnesia (PTA), and postconcussion syndrome (PCS). The development of LOC, PTA, and PCS greatly depends on the nature of the injury, and the degrees to which they develop are not necessarily consistent with symptom presentation. In recent years, sports concussions have become an area of increased research and public interest in the civilian population; similarly, blast TBI has gained attention in the military. Depending on the nature of the injury, different outcomes may result in the two populations. Consequently, treatments for mild TBI are rather diverse, and early intervention is the key to maximizing outcomes following a TBI. These topics and more will be discussed throughout this article.

Synaesthesia for pain is a phenomenon where a person experiences pain when observing or imagining another in pain. Anecdotal reports of this type of experience have most commonly occurred in individuals who have lost a limb. Distinct from phantom pain, synaesthesia for pain is triggered specifically in response to pain in another. Here, we provide the first preliminary investigation into synaesthesia for pain in amputees to determine the incidence and characteristics of this intriguing phenomenon. Self-referring amputees (n=74) answered questions on synaesthesia for pain within a broader survey of phantom pain. Of the participants, 16.2% reported that observing or imagining pain in another person triggers their phantom pain. Further understanding of synaesthesia for pain may provide a greater insight to abnormal empathic function in clinical populations as well as therapeutic intervention for at risk groups.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Since the beginning of the conflicts in Iraq and Afghanistan, there has been a dramatic increase in the number of military service members with single and multiple-limb amputations. Phantom limb pain (PLP) frequently develops in these individuals. As a result, identifying the best methods to treat PLP is critical. The review highlights areas of inquiry related to phantom pain, with a focus on PLP. REVIEW SUMMARY/RESULTS:This review discusses phantom sensations and phantom pain that arise after amputation of a body part, and summarizes the differences between the 2 conditions. Characteristics of PLP are also discussed, including the onset, duration, and location of PLP. Theories explaining the etiology and presence of PLP are reviewed, along with the numerous treatment options reported in the published data for such pain, including the use of mirrors for treating pain. We conclude with a description of one military hospital's experiences with PLP. CONCLUSIONS:Although more research has been done in previous years, this review identifies the need for continuing investigations. The etiology of PLP needs to be determined through more vigorous investigation, and a focus must be placed on defining treatment options in addition to mirror therapy that will improve the quality of life of those who suffer from this condition.

BACKGROUND:The slow Wallerian Degeneration (Wld(S)) gene specifically protects axonal and synaptic compartments of neurons from a wide variety of degeneration-inducing stimuli, including; traumatic injury, Parkinson's disease, demyelinating neuropathies, some forms of motor neuron disease and global cerebral ischemia. The Wld(S) gene encodes a novel Ube4b-Nmnat1 chimeric protein (Wld(S) protein) that is responsible for conferring the neuroprotective phenotype. How the chimeric Wld(S) protein confers neuroprotection remains controversial, but several studies have shown that expression in neurons in vivo and in vitro modifies key cellular pathways, including; NAD biosynthesis, ubiquitination, the mitochondrial proteome, cell cycle status and cell stress. Whether similar changes are induced in non-neuronal tissue and organs at a basal level in vivo remains to be determined. This may be of particular importance for the development and application of neuroprotective therapeutic strategies based around Wld(S)-mediated pathways designed for use in human patients. RESULTS:We have undertaken a detailed analysis of non-neuronal Wld(S) expression in Wld(S) mice, alongside gravimetric and histological analyses, to examine the influence of Wld(S) expression in non-neuronal tissues. We show that expression of Wld(S) RNA and protein are not restricted to neuronal tissue, but that the relative RNA and protein expression levels rarely correlate in these non-neuronal tissues. We show that Wld(S) mice have normal body weight and growth characteristics as well as gravimetrically and histologically normal organs, regardless of Wld(S) protein levels. Finally, we demonstrate that previously reported Wld(S)-induced changes in cell cycle and cell stress status are neuronal-specific, not recapitulated in non-neuronal tissues at a basal level. CONCLUSIONS:We conclude that expression of Wld(S) protein has no adverse effects on non-neuronal tissue at a basal level in vivo, supporting the possibility of its safe use in future therapeutic strategies targeting axonal and/or synaptic compartments in patients with neurodegenerative disease. Future experiments determining whether Wld(S) protein can modify responses to injury in non-neuronal tissue are now required.

Despite the amount of research that has been conducted on phantom limb pain (PLP), the etiology of the condition remains unknown, and treatment options are limited. After an individual loses a limb, the brain continues to detect the presence of the missing limb even though it is no longer attached to the body, likely through proprioceptive signals. The majority of patients with amputations either report the feeling of volitional control over their phantom or a phantom limb that is frozen in a specific position. Many patients also experience PLP. Here we propose a new theory, termed "proprioceptive memory," which may explain some of the unique experiences amputees encounter. We also suggest that memories of the limb's position prior to amputation remain embedded within an individual's subconscious, and pain memories that may be associated with each limb position contribute not only to PLP, but to the experience of a fixed or frozen limb. We suspect that there are memory networks for pain--and other sensations, either positive or negative--that are associated with each limb position, and propose that these memories evolved to protect our bodies from repeated injury. A discussion of mirror therapy as a treatment option for PLP is also provided, as well as an explanation for the efficacy of mirror therapy. The paper offers a unique insight into how and why amputees experience these unusual phenomena.

OBJECTIVES/OBJECTIVE:Subjects who have suffered limb amputations are known to have physiological alterations of their body's representation, or schema. Such changes of brain function might alter the right-left spatial allocation of attention. The goal of this study was to learn if, compared to normal subjects, limb amputees had alterations of right-left spatial attention. METHODS:The subjects were veterans with amputation of one upper or lower limb. All subjects performed horizontal line bisections in their left, middle and right body-centered space. RESULTS:Following right upper limb amputation, there appears to be a reduction of the normal left-sided bias (pseudoneglect) primarily for lines presented in the right body hemispace. CONCLUSIONS:This amputation-induced alteration of attentional bias might be related to changes in the body schema, a compensatory strategy, or alterations of scanning patterns. Further studies are needed to reproduce these results and to learn the underlying brain mechanism.

OBJECTIVE:To study the effectiveness of botulinum toxin type A (BTX-A) therapy for residual limb hyperhidrosis, prosthesis fit and function, and residual and phantom limb pain in patients with limb amputation. DESIGN/METHODS:Consecutive case series. SETTING/METHODS:Outpatient physical medicine and rehabilitation clinic. PARTICIPANTS/METHODS:Walter Reed Army Medical Center patients (N=8) with unilateral traumatic upper- or lower-limb amputation. INTERVENTION/METHODS:BTX-A was injected transdermally in a circumferential pattern around the residual limb by using a 1-cm matrix grid. MAIN OUTCOME MEASURE/METHODS:A 10-cm continuous Likert visual analog scale was used to assess residual limb sweating and pain and prosthesis fit and function before and 3 weeks after BTX-A injections. RESULTS:Patients reported a significant reduction in sweating and improvement in prosthesis fit and function after treatment. However, residual limb and phantom pain were unaffected by treatment. CONCLUSIONS:BTX-A may be an effective treatment for residual limb hyperhidrosis, resulting in subjective improvement in prosthesis fit and functioning. BTX-A should be considered as a method to manage excessive sweating in the residual limb of traumatic amputees.