Virtual movements activate primary sensorimotor areas in amputees: report of three cases

OBJECTIVE: In our multidisciplinary pain clinic, three patients with amputated limbs and with surgical indications for chronic motor cortex stimulation for phantom limb pain were selected for their ability to voluntarily move the missing limb. The sensation of being able to move a missing limb at will occurs quite frequently among traumatic amputees, but the ability to control it sufficiently to perform a functional magnetic resonance imaging (fMRI) examination is more rarely encountered. We used motor fMRI to study these virtual movements. METHODS: In two patients with upper-limb amputations, movements of the stump, the normal hand, and the missing arm were studied. In a third patient with both legs amputated, movements of the stumps and of the missing feet were studied. The fMRI data were analyzed with the Statistical Parametric Map 96 software and reformatted for integration into anatomic slices. RESULTS: Virtual movements of the missing limbs produced contralateral primary sensorimotor cortex and central sulcus activations in the patients with upper-limb amputation. Interhemispheric and bilateral activations were found in the patient with both legs amputated. These activation areas were different from the stump activation areas. Additionally, the significance thresholds chosen to generate the activation maps in virtual movements (although individual) were globally the same as those used to detect motor activation in the normal side of the patients. CONCLUSION: Cortical areas devoted to the missing limb seem to persist for several years after amputation. The precentral activations found in our patients are in agreement with the statement that the neural mechanisms involved in the mental representation of an action and in its execution are the same. Data from fMRI can be used to evaluate phantom limb virtual movements and to study cortical reorganization phenomena that can appear with time or as a result of some therapies. In these patients, fMRI data may be useful in assisting the neurosurgeon in the placement of chronic motor cortex electrodes.     

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.     

Methodological and technical issues for integrating functional magnetic resonance imaging data in a neuronavigational system

OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.     

Cortical areas involved in virtual movement of phantom limbs: comparison with normal subjects

OBJECTIVE: To demonstrate that amputees performing "virtual" movements of their amputated limb activate cortical areas previously devoted to their missing limb, we studied amputees with functional magnetic resonance imaging (fMRI) and positron emission tomographic (PET) scans and compared the results with those of normal volunteers performing imaginary movements during fMRI acquisitions. METHODS: Ten amputees (age range, 33-92 yr; average age, 49 yr; six men and four women; eight upper-limb and two lower-limb amputations) able to move their phantom limb at will were studied by fMRI (all patients) and PET scan (seven patients). The time between amputation and fMRI and PET studies ranged from 1 to 27 years (average, 13 yr). Patients were asked to perform virtual movements of the amputated limb and normal movements of the contralateral normal limb according to the functional images acquisition procedure. Movements of the stump were also used to differentiate stump cortical areas from virtual movement-activated areas. Ten right-handed volunteers, age- and sex-matched to the amputees, were also studied by fMRI. All volunteers were asked to perform four tasks during their fMRI study: imaginary movements of their right arm (1 task) and foot (1 task) and real movements of their left arm (1 task) and foot (1 task). RESULTS: In amputees, virtual movements of the missing limbs produced contralateral primary sensorimotor cortex activation on both fMRI and PET scans. These activation areas, different from the stump activation areas, were similar in location to contralateral normal limb-activated areas. Quantitatively, in two amputees who claimed to be able to perform both slow and fast virtual movements, regional cerebral blood flow measured by PET scan in the precentral gyrus increased significantly during fast movements in comparison with slow virtual movements. In normal subjects, significant differences between real versus imaginary fMRI activations were found (for both foot and hand movements); imaginary right hand and foot tasks activated primarily the contralateral supplementary motor areas, with no significant activation detected in the contralateral precentral or postcentral gyri. CONCLUSION: Primary sensorimotor cortical areas can be activated by phantom-limb movements and thus can be considered functional for several years or decades after amputation. In this study, we found that the location of the activation of these areas is comparable to that of activations produced by normal movements in control subjects or in amputees.     

Phantom limb pain originates from dysfunction of the primary motor cortex

Accumulated knowledge indicates that phantom limb pain is a phenomenon of the central nervous system that is related to plastic changes at several levels of the nervous systems. Especially, reports using patients with neuropathic pain clearly indicate the sensorimotor cortex as underlying mechanisms of phantom limb and its pain. Here, we focus the notion that limb amputation or deafferentation results in plasticity of connections between the brain and the body, and that the cortical motor representation of the missing or deafferented limb seemingly disappears. Meanwhile, the sensory representation of the limb does not disappear and thereby patients feel phantom limbs. We propose that dissociation between motor and sensory representations in the primary motor cortex induces pathologic pain and reconcile of sensorimotor integration of the limb would alleviate pain, on the basis of our neurorehabilitation approaches and artificial neuromodulation strategies.     

Phantom limb pain: cortical plasticity and novel therapeutic approaches

Phantom limb pain is still a very frequent consequence of peripheral deafferentation or amputation of a limb. Recent findings from animal and neuroimaging studies suggest that phantom limb pain might be a central phenomenon, related to changes in the cortical, thalamic and spinal representation of the painful limb, and might be a type of somatosensory pain memory. Based on these assumptions, new treatment approaches focus on sensory discrimination training or motor cortex stimulation in an effort to influence cortical reorganization. Prevention of perpetuation of a somatosensory pain memory might also be possible through pharmacological agents such as N-methyl-D-aspartate antagonists and gamma-aminobutyric acid agonists, substances that have been shown to influence and prevent cortical reorganization.     

Image-guided motor cortex stimulation in patients with central pain.

According to recent clinical data, motor cortex stimulation (MCS) is an alternative treatment for central pain syndromes. We present our minimally invasive technique of image guidance for the placement of the motor cortex-stimulating electrode and assess the clinical usefulness of both neuronavigation and vacuum headrest. Five patients suffering from central pain underwent MCS with the guidance of a frameless stereotactic system (BrainLab AG, Munich, Germany). The neuronavigation was used for identification of the precentral gyrus and accurate planning of the single burr hole. The exact location was reconfirmed by an intraoperative stimulation test. Postoperative clinical and neuroradiological evaluations were performed in each patient. The navigation system worked properly in all 5 neurosurgical cases. Determination of the placement of stimulating electrode was possible in every case. All patients obtained postoperative pain relief. No surgical complication occurred, and the postoperative course was uneventful in all patients. This preliminary experience may confirm image guidance as a useful tool for the surgery of MCS. Additionally, minimal and safe exposure can be achieved using a single burr hole and vacuum headrest.     

Deep brain stimulation and frameless stereotactic radiosurgery in the treatment of bilateral parkinsonian tremor: target selection and case report of two patients

Considerable positive experience in functional radiosurgery has been reported since Leksell??s first experience in 1951, but the development of frameless radiosurgery was been limited because of the difficulty of identifying invisible functional targets. In this paper we report on two cases of bilateral parkinsonian tremor successfully treated with DBS on one side and with frameless radiosurgery on the contralateral side. We focus on the methodology developed to define the three-dimensional target coordinates for frameless radiosurgery. Two patients suffering from a disabling upper-limb parkinsonian tremor underwent frameless radiosurgical thalamotomy. To accurately identify the treatment target the CT gantry was treated as a stereotactic frame; a rototranslation between the origin of the screen and the origin of the stereotactic atlas allowed us to obtain atlas-registered 3D coordinates of each point on the CT axial brain slices. Both patients achieved complete bilateral tremor control by unilateral radiosurgery and contralateral DBS. We developed a method for determining the 3D coordinates of a known functional target to treat with frameless radiosurgery. Based on the initial experiences, frameless radiosurgery appears to be an alternative treatment for Parkinsonian upper limb tremor in the presence of increased surgical risks for DBS placement.     

A New Cortical Electrode for Neuronavigation-Guided Intraoperative Neurophysiological Monitoring: Technical Note

Intraoperative neurophysiological mapping and monitoring of eloquent brain areas can be combined with image-guided localisation to enhance the safety and efficacy of surgical procedures in the motor cortex. We designed a new type of cortical electrode which can be repeatedly placed on the cortical surface and allows accurate and reproducible stimulation by means of a navigation pointer. The newly designed device consists of a monopolar electrode contact for direct cortical stimulation, housed in a holder which allows placement, easy removal, and precise repeated placement of a surgical navigation pointer. It can be used for navigation-guided, high-frequency anodal monopolar cortical stimulation (MCS) for the mapping of eloquent cortex, and for monitoring of motor pathways. While the cortex is stimulated, compound muscle action potentials (CMAP) are recorded from muscles of the contralateral extremities and are assessed both qualitatively and quantitatively. When the device is used in combination with intraoperative navigation, the stimulation sites may optionally be registered or displayed on the system monitor. This allows repeated pinpointing and obviates the need for strip or grid electrodes in the operative field; although such electrodes may be useful for continuous monitoring, they often are in the surgeon's way. In addition, the primary and supplementary motor cortex can be mapped by determining the location of the sites of stimulation on surface-projected images of the cerebral cortex.     

Brain plasticity and hand surgery: an overview

The hand is an extension of the brain, and the hand is projected and represented in large areas of the motor and sensory cortex. The brain is a complicated neural network which continuously remodels itself as a result of changes in sensory input. Such synaptic reorganizational changes may be activity-dependent, based on alterations in hand activity and tactile experience, or a result of deafferentiation such as nerve injury or amputation. Inferior recovery of functional sensibility following nerve repair, as well as phantom experiences in virtual, amputated limbs are phenomena reflecting profound cortical reorganizational changes. Surgical procedures on the hand are always accompanied by synaptic reorganizational changes in the brain cortex, and the outcome from many hand surgical procedures is to a large extent dependent on brain plasticity.     

Sensorimotor cortical activity in patients with complete spinal cord injury: a functional magnetic resonance imaging study

Residual activation of the cortex was investigated in nine patients with complete spinal cord injury between T6 and L1 by functional magnetic resonance imaging (fMRI). Brain activations were recorded under four conditions: (1) a patient attempting to move his toes with flexion-extension, (2) a patient imagining the same movement, (3) passive proprio-somesthesic stimulation of the big toes without visual control, and (4) passive proprio-somesthesic stimulation of the big toes with visual control by the patient. Passive proprio-somesthesic stimulation of the toes generated activation posterior to the central sulcus in the three patients who also showed a somesthesic evoked potential response to somesthesic stimulation. When performed under visual control, activations were observed in two more patients. In all patients, activations were found in the cortical areas involved in motor control (i.e., primary sensorimotor cortex, premotor regions and supplementary motor area [SMA]) during attempts to move or mental imagery of these tasks. It is concluded that even several years after injury with some local cortical reorganization, activation of lower limb cortical networks can be generated either by the attempt to move, the mental evocation of the action, or the visual feedback of a passive proprio-somesthesic stimulation.     

Intraoperative validation of functional magnetic resonance imaging and cortical reorganization patterns in patients with brain tumors involving the primary motor cortex.

OBJECT: The purpose of the present study was to compare the results of functional magnetic resonance (fMR) imaging with those of intraoperative cortical stimulation in patients who harbored tumors close to or involving the primary motor area and to assess the usefulness of fMR imaging in the objective evaluation of motor function as part of the surgical strategy in the treatment of these patients. METHODS: A total of 11 consecutive patients, whose tumors were close to or involving the central region, underwent presurgical blood oxygen level-dependent fMR imaging while performing a motor paradigm that required them to clench and spread their hands contra- and ipsilateral to the tumor. Statistical cross-correlation functional maps covering the primary and secondary motor cortical areas were generated and overlaid onto high-resolution anatomical MR images. Intraoperative electrical cortical stimulation was performed to validate the presurgical fMR imaging findings. In nine (82%) of 11 patients, the anatomical fMR imaging localization of motor areas could be verified by intraoperative electrical cortical stimulation. In seven patients two or more activation sites were demonstrated on fMR imaging, which were considered a consequence of reorganization phenomena of the motor cortex: contralateral primary motor area (nine patients), contralateral premotor area (four patients), ipsilateral primary motor area (two patients), and ipsilateral premotor area (four patients). CONCLUSIONS: Functional MR imaging can be used to perform objective evaluation of motor function and surgical planning in patients who harbor lesions near or involving the primary motor cortex. Correlation between fMR imaging findings and the results of direct electrical brain stimulation is high, although not 100%. Based on their study, the authors believe that cortical reorganization patterns of motor areas might explain the differences in motor function and the diversity of postoperative motor function among patients with central tumors.     

Visualisierung von Phantom- und Rückenschmerzen durch bildgebende Verfahren

If patients with chronic low back pain are stimulated in the painful region, an expanded representation of the back in the primary somatosensory cortex becomes visible that increases with chronicity. This "pain memory" might play an important role in the chronicity process. In patients with phantom limb pain, e.g. subsequent to the amputation of an arm or leg, a shift in the representation of neighboring areas into the deafferented area in primary somatosensory cortex has been observed. This reorganization of functional brain maps is not present in congenital amputees or amputees without phantom limb pain. The magnitude of such pain is positively correlated with this reorganization. We present a model of phantom limb pain that assigns an important role to pre-existing chronic pain. The modulation of plasticity and phantom limb pain by anesthesiological manipulation, the use of NMDA receptor antagonists and opioids is presented. Behaviorally relevant stimulation, e.g. by the use of a myoelectric prosthesis or sensory discrimination training can also influence the cortical somatosensory pain memory. More recent studies focus also on brain areas such as the cingulate gyrus believed to be involved in the affective processing of pain.     

Phantom limb pain: aspects of neuroplasticity and intervention

Phantom-limb pain is a common sequel of amputation, occurring in up to 80 % of the amputee population. It must be differentiated from non-painful phantom phenomena, residual-limb pain, and non-painful residual-limb phenomena. A comprehensive model of phantom-limb pain is presented that assigns a major role to pain occurring before the amputation and to central as well as peripheral changes related to it. Special emphasis is put on the role of cortical reorganization in the development of phantom limb pain. Finally, new approaches to the prevention and treatment of phantom limb pain are presented that have a positive influence on phantom limb pain by preventing or reversing cortical reorganization.     

Phantom limb pain during labour

We report the occurrence of severe phantom limb pain during labour. The patient, a 27-year-old, had had an above knee amputation performed 6 years earlier following a road traffic accident but had no previous history of phantom limb phenomena. However, during early labour, she complained of a severe phantom limb pain in her amputated leg; a continuous epidural block relieved her of the sensation and pain. The sensation did not return following delivery.     

Phantom limb pain

Almost everyone who has amputated a limb will experience a phantom limb. They have the vivid impression, that the limb is still present. 60 to 70% of these amputees will suffer from phantom limb pain. The present paper gives an overview of the incidence and the characteristics of the so called "post amputation syndrome". Possible mechanism of this phenomena are presented, including peripheral, spinal, and central theories. Treatment of phantom limb pain is sometimes very difficult. It includes drug therapy, psychological therapy, physiotherapy as well as the prevention of phantom limb pain with regional analgesia techniques.     

Motor cortex stimulation for phantom limb pain: comprehensive therapy with spinal cord and thalamic stimulation

The effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) were analyzed in 19 patients with phantom limb pain. All of the patients underwent SCS and, if the SCS failed to reduce the pain, the patients were considered for DBS and/or MCS. Satisfactory pain control for the long-term was achieved in 6 of 19 (32%) by SCS, 6 of 10 (60%) by DBS and 1 (20%) of 5 by MCS. SCS and DBS of the VC sometimes produced a dramatic effect on the pain, leading to a long pain-free interval and infrequent use of stimulation. The effects of both DBS of the VC and MCS were tested in four. One patient of them reported better pain control by MCS than by DBS, whereas two reported the opposite results. There is no evidence at present for an advantage of MCS over SCS and DBS of the VC in controlling phantom limb pain.     

Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments

OBJECTIVE: To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. METHODS: We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P < 0.001) or t test (P < 0.001) analysis. RESULTS: In 50 patients, a total of 85 functional areas were within 5 mm of the edge of a potentially resectable lesion. In 23 of these areas (27%), reduced fMRI signal in perilesional eloquent cortex in conjunction with preserved or increased signal in homologous contralateral brain areas revealed functional dominance opposite the side of the lesion. This suggested possible lesion-induced transhemispheric cortical reorganization to homologous brain regions (homotopic reorganization). In seven patients, however, the fMRI data were inconsistent with other methods of functional localization. In two patients with left inferior frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. CONCLUSION: Lesion-induced neurovascular uncoupling causing reduced fMRI signal in perilesional eloquent cortex, in conjunction with normal or increased activity in homologous brain regions, may simulate hemispheric dominance and lesion-induced homotopic cortical reorganization.     

Painful supernumerary phantom arm following motor cortex stimulation for central poststroke pain. Case report.

In this report, the authors describe a case in which the patient began to experience a supernumerary phantom arm after she received motor cortex stimulation for central pain. The patient had a history of right thalamocapsular stroke. It is speculated that the motor cortex activation triggered a response in the patient's parietal lobe, precipitating perception of the phantom limb. To the authors' knowledge this is the first reported case of its kind.     

Cortical sensory and motor response in a patient whose hand has been replanted: one-year follow up with functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to study how a replanted hand regained its cortical territory parallel to recovery. The cortical response to sensory stimulation shifts from an ipsilateral to a bilateral pattern, and then to a predominantly contralateral activation. The cortical response to motor stimulation was normal from the first investigation.