Phantom limb after stroke: An underreported phenomenon

The presence of a phantom limb (PL) resulting from a cerebral lesion has been reported to be a rare event. No prior study, however, has systematically investigated the prevalence of this syndrome in a group of post-stroke individuals. Fifty post-stroke individuals were examined with structured interview/questionnaire to establish the presence and perceptual characteristics of PLs. We document the presence of phantom experiences in over half of these individuals (n = 27). We provide details of these phantom experiences and further characterize these symptoms in terms of temporal qualities, posture, kinesthesia, and associated features. Twenty-two participants reported postural phantoms, which were perceived as illusions of limb position that commonly manifested while lying in bed at night - a time when visual input is removed from multi-sensory integration. Fourteen participants reported kinesthetic phantoms, with illusory movements ranging from simple single joint sensations to complex goal-directed phantom movements. A striking syndrome of near total volitional control of phantom movements was reported in four participants who had immobile plegic hands. Reduplicative phantom percepts were reported by only one participant. Similarly, phantom pain was present in only one individual - the sole participant with a pre-stroke limb amputation. The results suggest that stroke results in phantom experiences more commonly than previously described in the literature. We speculate that subtotal deafferance or defective motor efference after stroke may manifest intermittently as a PL.     

Incorporation of another person's limb into body image relieves phantom limb pain: A case study

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.     

Central mechanisms in phantom limb perception: the past, present and future

Phantom limbs provide valuable insight into the mechanisms underlying bodily awareness and ownership. This paper reviews the complexity of phantom limb phenomena (proprioception, form, position, posture and telescoping), and the various contributions of internal constructs of the body, or body schema, and neuromatrix theory in explaining these phenomena. Specific systems and processes that have received little attention in phantom limb research are also reviewed and highlighted as important future directions, These include prosthesis embodiment and extended physiological proprioception (i.e., the extension of the body's "area of influence" that thereby extends one's innate sense of proprioception, mirror neurons and cross-referencing of the phantom limb with the intact limb (and the related phenomena of perceiving referred sensations and mirrored movements in the phantom form the intact limb). The likely involvements of the body schema and the body-self neuromatrix, mirror neurons, and cross-callosal and ipsilateral mechanisms in phantom limb phenomena all suggest that the perception of a "normal" phantom limb (that is, a non-painful phantom that has the sensory qualities of an intact limb) is more than likely an epiphenomenon of normal functioning, action understanding and empathy, and potentially may even be evolutionarily adaptive and perhaps necessary. Phantom pain, however, may be a maladaptive failure of the neuromatrix to maintain global bodily constructs.     

Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain

ObjectiveThe role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity.MethodsCross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging.ResultsWe included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04).ConclusionThere is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity.SignificanceThese findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.     

The various forms of sensorimotor plasticity following limb amputation and their link with rehabilitation strategies

Limb amputation is characterized by complex and intermingled brain reorganization processes combining sensorimotor deprivation induced by the loss of the limb per se, and compensatory behaviors, such as the over-use of the intact or remaining limb. While a large body of evidence documents sensorimotor representation plasticity following arm amputation, less investigations have been performed to fully understand the use-dependent plasticity phenomenon and the role of behavioral compensation in brain reorganization. In this article, I will review the findings on sensorimotor plasticity after limb amputation, focusing on these two aspects: sensorimotor deprivation and adaptive patterns of limb usage, and describe the models that attempt to link these reorganizational processes with phantom limb pain. Two main models have been proposed: the maladaptive plasticity model which states that the reorganization of the adjacent cortical territories into the representation of the missing limb is proportional to phantom pain intensity, and the persistent representation model, which rather suggests that the intensity of residual brain activity associated with phantom hand movements scales with phantom limb pain intensity. I will finally illustrate how this fundamental research helps designing new therapeutic strategies for phantom plain relief.     

Chronic pain and distorted body image: Implications for multisensory feedback interventions

Individuals with chronic pain often show a distorted body image. Various studies demonstrated that improvements in body image go along with symptom improvement in chronic pain. This renders distorted body images a promising target for feedback intervention programs. We propose that interventions that comprise of virtual reality (VR) multisensory feedback training provide a promising new avenue for the treatment of chronic pain. Thus far, VR-based interventions have been primarily applied to distract patients from pain. Recently, first attempts have been made to apply VR-based interventions as active sensory feedback training. VR-based feedback training allows the dynamic modification of virtual limbs that are perceived as one’s own. This offers unique opportunities to target long-term associations between sensory input and pain in patients with chronic pain. We predict that multisensory VR feedback interventions could be effective in reducing fear-avoidance behavior and improving distorted body images. We review current developments and provide an outlook on future directions in the promising field of VR feedback interventions for the multisensory treatment of chronic pain.     

Understanding intracortical excitability in phantom limb pain: A multivariate analysis from a multicenter randomized clinical trial

ObjectivesTo explore associations of intracortical excitability with clinical characteristics in a large sample of subjects with phantom limb pain (PLP).MethodsAncillary study using baseline and longitudinal data from a large multicenter randomized trial that investigated the effects of non-invasive brain stimulation combined with sensorimotor training on PLP. Multivariate regression modeling analyses were used to investigate the association of intracortical excitability, measured by percentages of intracortical inhibition (ICI) and facilitation (ICF) with clinical variables.ResultsNinety-eight subjects were included. Phantom sensation of itching was positively associated with ICI changes and at baseline in the affected hemisphere (contralateral to PLP). However, in the non-affected hemisphere (ipsilateral to PLP), the phantom sensation of warmth and PLP intensity were negatively associated with ICI (both models). For the ICF, PLP intensity (baseline model only) and age (longitudinal model) were negatively associated, while time since amputation and amputation level (both for longitudinal model only) were positively associated in the affected hemisphere. Additionally, use of antidepressants led to lower ICF in the non-affected hemisphere for the baseline model while higher amputation level also led to less changes in the ICF.ConclusionResults revealed clear associations of clinical variables and cortical excitability in a large chronic pain sample. ICI and ICF changes appear not to be mainly explained by PLP intensity. Instead, other variables associated with duration of neuroplasticity changes (such as age and duration of amputation) and compensatory mechanisms (such as itching and phantom limb sensation) seem to be more important in explaining these variables.     

Metal bar prevents phantom limb motion: Case study of an amputation patient who showed a profound change in the awareness of his phantom limb

This case report describes an amputee (patient A.S., a 60-year-old male forelimb amputee) who had an extraordinary experience with a phantom limb. He complained that he could not move the wrist of his phantom limb because a metal bar was perceived to be grasped by the hand. As a solution for removing the metal bar, we invited the patient to undergo mirror reflection-induced visual feedback therapy. The patient reported that the metal bar previously grasped by his hand was successfully removed from the phantom during the course of therapy. Interestingly, this experience was accompanied by profound changes in the EMG modulation in the residual wrist muscles. In this article, the possible mechanisms underlying this interesting phenomenon will be discussed.     

NMDA-mediated mechanisms in cortical excitability changes after limb amputation

OBJECTIVES: The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain. MATERIALS AND METHODS: Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed. RESULTS: Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain. CONCLUSION: We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.     

Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment

Post-amputation phantom limb pain (PLP) is a widespread phenomenon that can have physical, psychological, and functional impacts on amputees who experience the condition. The varying presentations and mechanisms of PLP make it difficult to effectively provide long-term pain relief. Multiple neuromodulatory approaches to treating PLP have focused on electrical stimulation of the peripheral nervous system, with varying degrees of success. More recently, research has been done to study the effects of neuroprosthetic approaches on PLP. Neuroprosthetics combine the use of a functional prosthetic with stimulation to the peripheral nerves in the residual limb. Although many of the neuroprosthetic studies focus on improving function, several have shown preliminary evidence for the reduction of severity of PLP. In this review we provide an overview of the current understanding of the neurological mechanisms that initiate and sustain PLP, as well as the neuromodulatory and neuroprosthetic approaches under development for treatment of the condition. Muscle Nerve 59 :154–167, 2019     

Non-painful phantom limb phenomena in amputees: incidence, clinical characterstics and temporal course

58 patients undergoing limb amputation mainly because of peripheral vascular disease were interviewed by means of a standard questionnaire and examined 8 days, 6 months and 2 years after limb amputation regarding non-painful phantom limb phenomena. During the follow-up period, 41% of patients died. The incidence of phantom limb 8 days, 6 months and 2 years after limb loss was 84%, 90% and 71%, respectively. Phantom limb phenomena changed within the first half year after amputation from a mainly proximal and distal distribution to a mainly distal localized sensation. While approximately 3/4 of patients with phantom limb had kinaesthetic sensations in the limb (i.e. feeling of length, volume or other spatial sensation) during the first 6 months after amputation, less than 50% of patients had this later in the course; 30% of patients noticed a clear shortening of the phantom limb during the follow-up period. While the incidence of phantom limb did not decrease during the follow-up period, both the duration and frequency of phantom limb phenomena declined significantly. The distribution of non-painful and painful phantom limb did not differ significantly from each other. The present findings suggest that mechanisms both in periphery, spinal cord and brain participate in generating the phantom limb percept.     

Supernumerary phantom limb as a rare symptom of epileptic seizures--case report and literature review

Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70-year-old male patient with new-onset focal seizures with left-sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single-photon emission computed tomography (SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure-onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature.     

Nerve regeneration and reinnervation after limb amputation and replantation: clinical and physiological findings

A 22-year-old male was studied 3 1/2-4 1/2 years after a traumatic section-avulsion amputation of the left upper extremity at the level of the distal humerus. The arm was reattached after a cold ischemia time of 4-5 hours and good vascularization was obtained. The ulnar nerve was repaired early with an end-to-end juncture while the median and radial nerves were repaired after seven months delay using a combination of vascularized radial nerve and nonvascularized sural nerve grafts. Some intrinsic hand muscle function had recovered. Pin-prick and touch sensation was present in all digits, although localization of touch stimulation was poor. Evoked motor responses had recovered by 25-50% of control amplitude in ulnar-innervated and by 10-25% in median-innervated muscles. Amplitudes of sensory responses from digit V had recovered by 25% and from digits I and III by 1-5%. Fast-adapting touch receptors had become reinnervated. There was electrophysiological evidence of aberrant sensory regeneration and of abnormal connections between sensory and motor fibers. Digital blood flow measurements suggested the presence of vascular obstruction in vessels of the replanted upper extremity. However, the digital vasoconstriction during cold exposure indicated regeneration of sympathetic nerve fibers.     

Pediatric limb amputation: Aspects of coping and psychotherapeutic intervention

This paper addresses the assessment of and intervention with pediatric patients undergoing limb amputation. A multicomponent treatment package is advocated including the use of play and cognitive-behavioral strategies to enhance coping and adjustment to the loss of a limb.     

幻肢和余剩幻肢研究的历史性回顾及新病例报告(英文)

大脑通常决定人类对其周围环境的感受。幻肢是接受过截肢手术的人所产生的一种幻觉,他们总感觉失去的肢体仍存在于躯干上。揭开幻肢的成因已成为神经病学领域的一个研究热点。此外,一些病人中风后会感觉到除正常存在的双臂和双腿之外,还存在额外的肢体。这种复杂的、意识和知觉上的偏差称为余剩幻肢。本文主要就幻肢和余剩幻肢的病因及对其认识的历史性发展作一综述,并报告一例余剩幻肢患者 。     

Phantom Limb Pain Relieved with Different Modalities of Central Nervous System Stimulation: A Clinical and Functional Imaging Case Report of Two Patients

Phantom limb pain (PLP) is a type of neuropathic pain syndrome that has evoked much interest in scientific and clinical fields. The condition is often intractable and severely debilitating. Though there are anecdotal reports in the literature of successful management of individual cases with brain and spinal cord stimulation, it has not been possible to develop a system of management that is consistently successful, mainly due to the paucity of basic neurophysiological data about PLP and its pathways in the central nervous system (CNS). Functional imaging offers a way of collecting information about the basic mechanisms and pathways of PLP from patients without the excessive risk of more invasive penetrating electrode studies or the questionable reliability of animal data. There have been very few studies that have looked at the direct effect of CNS stimulation on regional brain activation and correlation with the pain state. We describe two cases of PLP that have been satisfactorily treated with CNS stimulation (motor cortex and then periventricular gray in one and spinal cord in the other) and have been subjected to single photon emission computed tomography (SPECT) studies when in pain and then during stimulation with recorded pain relief. We found that regardless of the site of stimulation in the CNS, pain relief is associated with blood flow changes in similar areas of the brain, mainly the parietal and cingulate cortex and also in the thalamic nuclei and the central gray matter. Further studies of this kind should reveal more about the complex mechanisms of PLP and other forms of neuropathic pain.     

幻肢和余剩幻肢研究的历史性回顾及新病例报告(英文)

大脑通常决定人类对其周围环境的感受。幻肢是接受过截肢手术的人所产生的一种幻觉,他们总感觉失去的肢体仍存在于躯干上。揭开幻肢的成因已成为神经病学领域的一个研究热点。此外,一些病人中风后会感觉到除正常存在的双臂和双腿之外,还存在额外的肢体。这种复杂的、意识和知觉上的偏差称为余剩幻肢。本文主要就幻肢和余剩幻肢的病因及对其认识的历史性发展作一综述,并报告一例余剩幻肢患者 。     

Pain after stroke: A review

Pain after stroke (PAS) is a common clinical problem that is both underdiagnosed and undertreated. Yet, it induces depression and cognitive troubles, and impairs quality of life. To provide tools for practitioners, this report describes the most common PAS syndromes, including central post-stroke pain, spasticity and contractures, shoulder pain and complex regional pain syndromes, as well as headache and chondrocalcinosis, along with their risk factors, their prevention and their specific treatments. In addition, to ensure that the compulsory post-stroke clinical assessment in France is optimal, it is recommended that clinicians be trained in how to diagnose and treat PAS, and even to prevent it by early identification of at-risk patients, with the aim to improve patients’ motor and cognitive functions and quality of life.