Psychophysiological stress responses in amputees with and without phantom limb pain

The present experiment tested the hypothesis that phantom limb pain amputees show a different pattern of psychophysiological reactivity to stress compared with painfree amputees. Six phantom limb pain (PLP) and five painfree upper-extremity amputees were administered two groups of tasks: stressful and relaxing. The measured dependent variables were skin temperature recorded at both stump and intact site, heart rate, blood pressure, subjective pain and stress ratings. Phantom limb pain patients were characterized by higher stump temperature compared with phantom limb painfree patients. This effect was observed during the whole recording. Consistently with the between-subjects effect, when PLP patients exhibited higher skin temperature (during relaxation, compared with during stressful tasks), they perceived more pain. The experiment showed higher cardiovascular reactivity in PLP patients, specifically to the stressful free-speech task, which focused on recollection of the amputation event. As compared with the painfree patients, during the personal stressor, PLP patients' heart rate and systolic blood pressure increased, indicating a greater sympathetic response. Results indicate that peripheral factors, such as stump temperature reliably differentiate PLP from painfree patients. Moreover, the clear cardiovascular hyperreactivity observed in PLP patients during their report of amputation suggests that PLP is associated with a long-term emotional memory for the painful experience of that event. These results are consistent with most reports in the literature relating phantom pain development to the experience of preamputation pain.     

Discrimination of phantom hand sensations elicited by afferent electrical nerve stimulation in below-elbow amputees.

The necessity for a sensory feedback system that would enhance patient acceptability of motorized hand prostheses is now generally acknowledged. Afferent electrical stimulation of the nerves in the amputation stump can convey sensory feedback from prostheses with the advantage of eliciting sensations in the phantom image of the lost hand. Experiments with percutaneous nerve stimulation of the amputation stump in below-elbow amputees showed that with stable electrode conditions, amplitude modulated stimulation was better than frequency modulated stimulation in terms of accuracy, delay, and transinformation both with intermittent and uninterrupted stimulation. With unstable electrode conditions, different results were noticed, since amplitude modulated stimulation is very sensitive even to minor changes in electrode position. It is concluded that afferent electrical nerve stimulation with adequate training and stable electrodes had characteristics of accuracy, transinformation and delay which are good enough to make it a suitable method of conveying information in a prosthesis feedback system.     

Stability of phantom limb phenomena after upper limb amputation: a longitudinal study

Amputees may experience stump pain (SP), phantom limb (PL) sensations, pain, and/or a general awareness of the missing limb. The mechanisms underlying these perceptions could involve nervous system neuroplasticity and be reflected in altered sensory function of the residual limb. Since little is known about the progression of post-amputation sensory phenomena over time, we longitudinally evaluated the stability of, and relationships among: 1) subjective reports of PL sensations, pain, awareness, and SP, 2) stump tactile and tactile spatial acuity thresholds, and 3) use of a functional vs. a cosmetic prosthesis in 11 otherwise healthy individuals with recent unilateral, traumatic upper-extremity amputation. Subjects were evaluated within 6 months and at 1-3 years after amputation. Processing of tactile sensory information from the stump remained stable over the study time period. PL awareness was frequent, stable over time, intense, and occurred with or without PL sensations. Functional prosthetic use correlated with stable vividness of PL awareness whereas subjects who used a cosmetic prosthesis had less vivid PL awareness at follow-up. Initial SP correlated with follow-up SP, the initial PL pain correlated with follow-up PL pain but neither initial nor follow-up SP appear to be related to follow-up PL pain after accounting for initial PL pain intensity. Neither limb temperature nor prosthesis-use correlated with the initial vs. follow-up change in PL pain intensity. These data provide evidence that PL pain described 1-3 years after an amputation is not related in any simple way to peripheral sensory function, SP, or limb temperature; and PL awareness but not PL pain may be influenced by the frequent use of a functional prosthesis.     

Preflight development of bilateral wing coordination in the chick (Gallus domesticus): Effects of induced bilateral wing asymmetry

The performance of bilaterally synchronous wing-flapping by chick hatchlings suggests but does not prove the existence of a bilateral coordinating mechanism. The present research tests for bilateral coordination by using the technique of induced asymmetry. The onset of bilateral wing coordination was defined as the age when induced bilateral asymmetry produced by right wing amputation, immobilization, or weighting influenced the drop-evoked flapping rate of the left wing. Unilateral right wing immobilization or weighting immediately before testing reduced the flapping rate of the contralateral left wing of 3–5-day chicks, the youngest examined. Weighted and unweighted wings flapped synchronously. Therefore, a mechanism which acts across the body midline to synchronize wing-flapping by slowing the rate of the more rapidly flapping wing to match that of its slower contralateral partner was present by 3–5 days. This is several days before the onset of flight. The flapping rate of the left wing of chicks that had their right wing amputated on Day 1 was similar in rate to that of intact chicks when tested at 7 and 13 days. “Wing-flapping” on the amputated side of some unilateral amputees was made visible by a prosthesis attached to the stump of the amputated wing. Bilaterally coordinated flapping in the unilateral amputees indicated that the sensory and trophic periphery of a given wing and flight-related adaptive significance are not necessary for the postnatal production of bilaterally synchronized wing-flapping. However, the slowed flapping produced by unilateral wing weighting or immobilization indicates that wing-flapping rate is modulated by sensory feedback, even at preflight stages.     

Effects of short-term training on sensory and motor function in severed nerves of long-term human amputees

Much has been studied and written about plastic changes in the CNS of humans triggered by events such as limb amputation. However, little is known about the extent to which the original pathways retain residual function after peripheral amputation. Our earlier, acute study on long-term amputees indicated that central pathways associated with amputated peripheral nerves retain at least some sensory and motor function. The purpose of the present study was to determine if these functional connections would be strengthened or improved with experience and training over several days time. To do this, electrodes were implanted within fascicles of severed nerves of long-term human amputees to evaluate the changes in electrically evoked sensations and volitional motor neuron activity associated with attempted phantom limb movements. Nerve stimulation consistently resulted in discrete, unitary, graded sensations of touch/pressure and joint-position sense. There was no significant change in the values of stimulation parameters required to produce these sensations over time. Similarly, while the amputees were able to improve volitional control of motor neuron activity, the rate and pattern of change was similar to that seen with practice in normal individuals on motor tasks. We conclude that the central plasticity seen after amputation is most likely primarily due to unmasking, rather than replacement, of existing synaptic connections. These results also have implications for neural control of prosthetic limbs.     

Non-invasive brain stimulation reveals reorganized cortical outputs in amputees

EMG responses to non-invasive electromagnetic brain stimulation (EMS) were recorded from arm muscles of congenital amputees. Responses were obtained with lower thresholds on the amputated than on the intact side and were evoked from a larger cortical area. Contracting muscles showed increased responses to EMS; the increase was more pronounced on the amputated side. Similar findings were obtained in one traumatic amputee who suffered an early amputation, but not in another patient with a late amputation. We conclude that in congenital amputees there is substantial reorganisation of the corticospinal system and that this may also occur in early traumatic cases.     

Characterizing reactive hyperemia via tissue reflectance spectroscopy in response to an ischemic load across gender,age, skin pigmentation and diabetes

Purpose: Pressure ulcers represent a major secondary complication for amputees with diabetes and further complications may arise since ulcers are particularly hard to heal in this population. This study characterized the hyperemic response to a localized ischemic load in people with diabetes and amputation and compared it to that of subjects without diabetes or amputation. Subjects: Case-control study matching subjects by gender, age, skin pigmentation, and smoking status. Methods: Applying 150 mmHg to the patellar tendon for 10 minutes induced reactive hyperemia (RH). Tissue reflectance spectroscopy measured hemoglobin (HbO₂) concentration in tissue before, during and after application of pressure. Refill time, Maximum HbO₂, Time@Max HbO₂, RH area and RH half-life characterized the RH response and were analyzed using ANOVA. All values up to a level of p <0.1 are presented. Results: Analysis included responses from 88 subjects. RH magnitude and temporal parameters varied across skin pigmentation; smokers showed a decreased RH magnitude; vasodilator users had greater RH temporal parameters; no evidence of differences were found across disease state or age. Conclusion: Decreased RH response in smokers and subjects with dark skin might indicate a reduced ability to recover from ischemia. The lack of difference in RH response between subjects with and without diabetes was consistent with studies using other disability groups and corroborates the theory that RH is locally mediated.     

Preserved grip selection planning in chronic unilateral upper extremity amputees

Upper limb amputees receive no proprioceptive or visual sensory feedback about their absent hand. In this study, we asked whether chronic amputees nevertheless retain the ability to accurately plan gripping movements. Fourteen patients and matched controls performed two grip selection tasks: overt grip selection (OGS), in which they used their intact hand to grasp an object that appeared in different orientations using the most natural (under- or overhand) precision grip, and prospective grip selection (PGS), in which they selected the most natural grip for either hand without moving. We evaluated planning accuracy by comparing concordance between grip preferences expressed in PGS vs. OGS for the intact hand and PGS vs. the inverse of OGS responses for the affected hand. Overall, amputees showed no deficits in the accuracy of grip selection planning based on either hand and a consistent preference for less awkward hand postures. We found no evidence for a speed-accuracy tradeoff. Furthermore, selection accuracy did not depend on phantom mobility, phantom limb pain, time since amputation, or the residual limb’s shoulder posture. Our findings demonstrate that unilateral upper limb amputees retain the ability to plan movements based on the biomechanics of their affected hand even many years after limb loss. This unimpaired representation may stem from persistent higher-level activity-independent internal representations or may be sustained by sensory feedback from the intact hand.     

Motor control over the phantom limb in above-elbow amputees and its relationship with phantom limb pain

Recent evidence shows that the primary motor cortex continues to send motor commands when amputees execute phantom movements. These commands are retargeted toward the remaining stump muscles as a result of motor system reorganization. As amputation-induced reorganization in the primary motor cortex has been associated with phantom limb pain we hypothesized that the motor control of the phantom limb would differ between amputees with and without phantom limb pain. Eight above-elbow amputees with or without pain were included in the study. They were asked to produce cyclic movements with their phantom limb (hand, wrist, and elbow movements) while simultaneously reproducing the same movement with the intact limb. The time needed to complete a movement cycle and its amplitude were derived from the kinematics of the intact limb. Electromyographic (EMG) activity from different stump muscles and from the homologous muscles on the intact side was recorded. Different EMG patterns were recorded in the stump muscles depending on the movement produced, showing that different phantom movements are associated with distinct motor commands. Phantom limb pain was associated with some aspects of phantom limb motor control. The time needed to complete a full cycle of a phantom movement was systematically shorter in subjects without phantom limb pain. Also, the amount of EMG modulation recorded in a stump muscle during a phantom hand movement was positively correlated with the intensity of phantom limb pain. Since phantom hand movement–related EMG patterns in above-elbow stump muscles can be considered as a marker of motor system reorganization, this result indirectly supports the hypothesis that amputation-induced plasticity is associated with phantom limb pain severity. The discordance between the (amputated) hand motor command and the feedback from above-elbow muscles might partially explain why subjects exhibiting large EMG modulation during phantom hand movement have more phantom limb pain.     

A model for prediction of failure in amputation of the lower limb

A logistic regression analysis of eighteen variables in eighty-three lower limb amputations was performed in order to predict stump failure. Five variables were identified as having a significant effect on the logistic model: Age had an inverse relation to failure rate (p less than 0.005). This effect was mediated through a subgroup of 23 patients who had had a vascular operation (p less than 0.02), as this group had a higher failure rate and were younger than those without previous vascular surgery. Furthermore, the surgical experience (p less than 0.005) was of major importance for stump failure. Experienced surgeons had a failure rate of 2% while less experienced had a rate of 29% (p less than 0.001). In addition, it was confirmed that the higher the skin perfusion pressure (p less than 0.05) and the amputation level, (p less than 0.05) the better the healing. A model including "skin perfusion pressure," "previous vascular surgery," "amputation level" and "surgical experience" had a good predictive capability with a misclassification rate of 0.08-0.11. Therefore it is suggested that a logistic model including these variables could be a helpful tool to predict the risk of stump failure.     

Effect of modafinil on cerebral blood flow of anaesthetised rats

Primary sensory and motor areas of the cerebral cortex contain organised maps of the body. These maps appear to reorganise after damage to the peripheral parts of the sensory or motor systems, so that the cortical representation of undamaged structures expands at the expense of the damaged parts. Several studies in animals have suggested that decreased activity of the inhibitory GABAergic neurones is responsible for driving these changes. However, whether similar mechanisms sustain the effects in the longer term in humans is unknown. The present study addressed this question by examining reorganisation of sensorimotor areas of cortex in six unilateral upper limb amputees several years after the initial injury. We measured two independent indices of GABAergic function. Volumes of distribution of GABA(A) receptors were determined from 11C-flumazenil binding measured with positron emission tomography (PET). The strength of inhibition in the motor cortex was measured with paired-pulse transcranial magnetic stimulation. In the six amputees taken as a whole and compared with 24 normal subjects, there was a highly significant increase in 11C-flumazenil binding in the upper limb region of primary sensorimotor cortex bilaterally and in medial frontal cortex of the hemisphere contralateral to the amputation. Surprisingly, however, there was no change in the time course or strength of intra-cortical inhibition in the motor cortex of the amputees compared with matched control subjects. The increased 11C-flumazenil binding may reflect up-regulation of GABA(A) receptors to compensate for a decrease in the GABA content or activity of inhibitory neurones. Up-regulation of GABA(A) receptors may also indicate that long-term changes require stabilisation of cortical organisation.     

Effect of speed on the energy cost of walking in unilateral traumatic lower limb amputees

In this work, the effect of walking speed on the energy expenditure in traumatic lower-limb amputees was studied. The oxygen consumption was measured in 10 transfemoral amputees, 9 transtibial amputees and 13 control subjects, while they stood and walked at different speeds from 0.3 m s(-1) to near their maximum sustainable speed. Standing energy expenditure rate was the same in lower-limb amputees and in control subjects (approximately 1.85 W kg(-1)). On the contrary, during walking, the net energy expenditure rate was 30-60% greater in transfemoral amputees and 0-15% greater in transtibial amputees than in control subjects. The maximal sustainable speed was about 1.2 m s(-1) in transfemoral amputees and 1.6 m s(-1) in transtibial amputees, whereas it was above 2 m s(-1) in control subjects. Among these three groups, the cost of transport versus speed presented a U-shaped curve; the minimum cost increased with the level of amputation, and the speed at which this minimum occurred decreased.     

Risk of failure during gait for direct skeletal attachment of a femoral prosthesis: A finite element study

Direct skeletal attachments for transfemoral amputees have been the subject of clinical trials since the early nineties. This method of attachment allows the amputee an unrestricted range of motion around the hip joint, better sitting comfort, improved sensory feedback through osseoperception, improved limb control and reduced soft tissue problems. However, the length of the rehabilitation period is perceived as a shortcoming by the amputees and the clinicians. The aim of the present study is to estimate the risk of failure during gait, for a patient with direct skeletal attachment of a femoral prosthesis, using finite element analysis (FEA).Material properties and loads were derived from subject-specific data and implant stability assumed secured by bone ingrowth into a porous implant surface. A simplified FEA was used to optimize the implant geometry with respect to load bearing capacity. The resulting geometry was then implemented in a subject-specific FE study. The results indicate that the risk of failure for the implant system is approximately three times greater than what can be expected for an intact femur.The main conclusion, based on the risk of failure factors calculated, is that it is likely that a porous-coated implant could be beneficial for osseointegrated fixation. It is also suggested that the proposed methodology can be used in future studies exploring the mechanical stability of osseointegrated fixation in the view of improving direct skeletal attachments for lower limb amputees.     

Unexpected reorganization of somatosensory cortex in a raccoon with extensive forelimb loss

Electrophysiological recordings were made from primary somatosensory cortex in a raccoon that had suffered a traumatic amputation of the forearm some time prior to its capture. Neurons in the affected forepaw region of sensory cortex were not silent but responded to cutaneous or neuroma activation of the remaining forearm stump. In addition, cells at many sites were responsive to tactile stimulation of the glabrous skin of the hindpaw ipsilateral to the damage. This indicates that the cortical plasticity following peripheral nerve damage can occur over much larger regions of cortex than was previously thought. An unmasking of silent thalamocortical terminals is not likely to be the mechanism underlying this plasticity in the raccoon.     

Role of development in reorganization of the SI forelimb-stump representation in fetally,neonatally, and adult amputated rats

Rats that sustain forelimb removal on postnatal day (P) 0 exhibit numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to hindlimb stimulation when cortical GABAA+B receptors are blocked. Most of these hindlimb inputs originate in the medial SI hindlimb representation. Although many forelimb-stump sites in these animals respond to hindlimb stimulation, very few respond to stimulation of the face (vibrissae or lower jaw), which is represented in SI just lateral to the forelimb. The lateral to medial development of SI may influence the capacity of hindlimb (but not face) inputs to "invade" the forelimb-stump region in neonatal amputees. The SI forelimb-stump was mapped in adult (>60 days) rats that had sustained amputation on embryonic day (E) 16, on P0, or during adulthood. GABA receptors were blocked and subsequent mapping revealed increases in nonstump inputs in E16 and P0 amputees: fetal amputees exhibited forelimb-stump sites responsive to face (34%), hindlimb (10%), and both (22%); neonatal amputees exhibited 10% face, 39% hindlimb, and 5% both; adult amputees exhibited 10% face, 5% hindlimb, and 0% both, with approximately 80% stump-only sites. These results indicate age-dependent differences in receptive-field reorganization of the forelimb-stump representation, which may reflect the spatiotemporal development of SI. Results from cobalt chloride inactivation of the SI vibrissae region and electrolesioning of the dysgranular cortex suggest that normally suppressed vibrissae inputs to the SI forelimb-stump area originate in the SI vibrissae region and synapse in the dysgranular cortex.     

Finite Element Analysis of Donning Procedure of a Prosthetic Transfemoral Socket

Lower limb amputation is a severe psychological and physical event in a patient. A prosthetic solution can be provided but should respond to a patient-specific need to accommodate for the geometrical and biomechanical specificities. A new approach to calculate the stress–strain state at the interaction between the socket and the stump of five transfemoral amputees is presented. In this study the socket donning procedure is modeled using an explicit finite element method based on the patient-specific geometry obtained from CT and laser scan data. Over stumps the mean maximum pressure is 4 kPa (SD 1.7) and the mean maximum shear stresses are 1.4 kPa (SD 0.6) and 0.6 kPa (SD 0.3) in longitudinal and circumferential directions, respectively. Locations of the maximum values are according to pressure zones at the sockets. The stress–strain states obtained in this study can be considered more reliable than others, since there are normal and tangential stresses associated to the socket donning procedure.     

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Tenascin localization in skin wounds of the adult newt Notophthalmus viridescens.

Earlier studies have shown that the extracellular matrix (ECM) protein tenascin (TN) is present between uninjured epidermal cells of urodele appendages, but is absent from most of the mesenchymally derived ECM. Following appendage amputation, this distribution is reversed. TN is lost from the epidermis and appears in the ECM of the stump and the regeneration blastema. In the present study, monoclonal and polyclonal antibodies to TN were used to localize this protein immunohistochemically in limbs of the adult urodele Notophthalmus viridescens at various stages following skin removal with or without damage to underlying muscle to determine 1) if the loss of TN by the epidermis and its gain by mesenchymal tissues occurs in wounds that do not require regulation by epigenetic mechanisms, and 2) if TN is present in the provisional wound matrix beneath migrating epidermal cells. In addition, skin explants were cultured on TN-coated dishes to learn if TN possesses active sites that can support epidermal cell migration. The results indicate that simple wounding leads to the same TN patterns as occurs following limb amputation. Tenascin loss from the epidermis could be seen as early as 6 hr after wounding, a time during which migrating epidermal cells are moving over the wound bed. During this period, there was no evidence of TN in the provisional wound matrix. In contrast to collagen, which supports considerable epidermal cell migration from skin explants, TN allowed no more migration than did the inactive protein, myoglobin.     

Tenascin localization in skin wounds of the adult newt Notophthalmus viridescens

Earlier studies have shown that the extracellular matrix (ECM) protein tenascin (TN) is present between uninjured epidermal cells of urodele appendages, but is absent from most of the mesenchymally derived ECM. Following appendage amputation, this distribution is reversed. TN is lost from the epidermis and appears in the ECM of the stump and the regeneration blastema. In the present study, monoclonal and polyclonal antibodies to TN were used to localize this protein immunohistochemically in limbs of the adult urodele Notophthalmus viridescens at various stages following skin removal with or without damage to underlying muscle to determine (1) if the loss of TN by the epidermis and its gain by mesenchymal tissues occurs in wounds that do not require regulation by epigenetic mechanisms, and (2) if TN is present in the provisional wound matrix beneath migrating epidermal cells. In addition, skin explants were cultured on TN-coated dishes to learn if TN possesses active sites that can support epidermal cell migration. The results indicate that simple wounding leads to the same TN patterns as occurs following limb amputation. Tenascin loss from the epidermis could be seen as early as 6 hr after wounding, a time during which migrating epidermal cells are moving over the wound bed. During this period, there was no evidence of TN in the provisional wound matrix. In contrast to collagen, which supports considerable epidermal cell migration from skin explants, TN allowed no more migration than did the inactive protein, myoglobin.     

Rehabilitation of the elderly amputee.

A rehabilitation service based in a department of geriatric medicine and dealing exclusively with amputees aged 65 years or over, is described. Provision of prostheses has been expedited, and the multi-disciplinary approach of the department has been beneficial in rehabilitation especially of the amputee with multiple pathology. The experience of the first 146 patients with an average age of 74.1 years is reviewed. Discharge home was achieved in 77.6% of the patients provided with a prosthesis and in a small multi-centre study of the post discharge status of 20 elderly amputees it was found that over 90% used their prosthesis regularly and the great majority were independent in the activities of daily living. Although BKA (Below knee amputation) is preferable to AKA (Above knee amputation), the functional benefit in this age group is not always as significant as traditional attitudes would suggest whereas a failed BKA has serious consequences in terms of psychological impact, morbidity and length of hospital stay. In order to minimise the number of BKA's requiring revision or re-amputation every effort should be made to ensure that the initial procedure is carried out by a surgeon with experience of amputation in this age group. Limb provision is cost effective and the frequent difficulty with regard to the financing of prostheses for elderly amputees is counter-productive.