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.     

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.     

Chronic motor cortex stimulation for phantom limb pain: a functional magnetic resonance imaging study: technical case report

OBJECTIVE AND IMPORTANCE: Chronic motor cortex stimulation has provided satisfactory control of pain in patients with central or neuropathic trigeminal pain. We used this technique in a patient who experienced phantom limb pain. Functional magnetic resonance imaging (fMRI) was used to guide electrode placement and to assist in understanding the control mechanisms involved in phantom limb pain. CLINICAL PRESENTATION: A 45-year-old man whose right arm had been amputated 2 years previously experienced phantom limb pain and phantom limb phenomena, described as the apparent possibility of moving the amputated hand voluntarily. He was treated with chronic motor cortex stimulation. INTERVENTION: Data from fMRI were used pre- and postoperatively to detect shoulder and stump cortical activated areas and the "virtual" amputated hand cortical area. These sites of preoperative fMRI activation were integrated in an infrared-based frameless stereotactic device for surgical planning. Phantom limb virtual finger movement caused contralateral primary motor cortex activation. Satisfactory pain control was obtained; a 70% reduction in the phantom limb pain was achieved on a visual analog scale. Postoperatively and under chronic stimulation, inhibiting effects on the primary sensorimotor cortex as well as on the contralateral primary motor and sensitive cortices were detected by fMRI studies. CONCLUSION: Chronic motor cortex stimulation can be used to relieve phantom limb pain and phantom limb phenomena. Integrated by an infrared-based frameless stereotactic device, fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication. Pain control mechanisms and cortical reorganization phenomena can be studied by the use of fMRI.     

Efficacy of motor cortex stimulation for intractable central neuropathic pain: comparison of stimulation parameters between post-stroke pain and other central pain

Motor cortex stimulation (MCS) has now become the preferred option for neurosurgical management of intractable central neuropathic pain such as post-stroke pain and trigeminal neuropathic pain. However, the efficacy of MCS for other central neuropathic pain such as pain resulting from spinal cord or brainstem lesions is unclear. We retrospectively reviewed 11 consecutive patients with intractable central neuropathic pain who underwent MCS in our institution. Eight patients had poststroke pain caused by thalamic hemorrhage (n = 5) or infarction (n = 3) (thalamic group). Two patients had postoperative neuropathic pain caused by spinal cord lesions, and one patient had facial pain caused by a brainstem lesion associated with multiple sclerosis (brainstem-spinal group). Visual analog scale and stimulation parameters were evaluated at 1 and 6 months postoperatively. MCS was effective for six of eight patients in the thalamic group, and all three patients in the brainstem-spinal group. These efficacies continued for 6 months after surgery without significant change in the stimulation parameters compared with the parameters at 1 month in both groups. The mean amplitude at 1 month and frequency at 6 months after surgery were significantly higher in the brainstem-spinal group than the thalamic group, although the patient number was small. MCS is effective for other central neuropathic pain, but higher intensity stimulation parameters may be necessary to gain adequate pain reduction.     

Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomized double-blind trial

OBJECT: In this study the authors used a double-blind protocol to assess the efficacy of motor cortex stimulation (MCS) for treating neuropathic pain. METHODS: Eleven patients with unilateral neuropathic pain (visual analog scale [VAS] score 8-10) of different origins and topography were selected for MCS. A 20-contact grid was implanted through a craniotomy centered over the motor cortex contralateral to the painful area. The motor cortex strip was identified using neuroimages, somatosensory evoked potentials, acute electrical stimulation, and corticocortical evoked potentials. Subacute therapeutic stimulation trials allowed the authors to determine the most efficient pair of contacts to use for long-term MCS. The grid was replaced with a 4-contact electrode connected to an internalized stimulator. Bipolar stimulation at a 40-Hz frequency, 90-micro sec pulse width, amplitude 2-7 V, and 1 hour in "ON" and 4 hours in "OFF" mode was used. Pain was evaluated using the VAS, Bourhis, and McGill pain scales applied each month for 1 year. At Day 60 or 90, the stimulators were turned to OFF mode for 30 days in a randomized, double-blind fashion. The statistical tool used was the Wilcoxon test. RESULTS: Three patients did not report improvement in the subacute trial and were excluded from long-term MCS; the remaining patients underwent long-term stimulation. Significant improvement of pain was induced by MCS (p < 0.01); this persisted during the follow-up period. Turning stimulation to OFF mode increased pain significantly (p < 0.05). Improvement at 1 year was >or= 40% (40-86%) in all cases. CONCLUSIONS: Motor cortex stimulation is an efficient treatment for neuropathic pain, according to an evaluation facilitated by a double-blind maneuver. Subacute stimulation trials are recommended to determine the optimum motor cortex area to be stimulated and to identify nonresponders.     

Efficacy and safety of motor cortex stimulation for chronic neuropathic pain: critical review of the literature

OBJECT: The authors systematically reviewed the published literature to evaluate the efficacy of and adverse effects after motor cortex stimulation (MCS) for chronic neuropathic pain. METHODS: A search of the PubMed database (1991-2006) using the key words "motor cortex," "stimulation," and "pain" yielded 244 articles. Only original nonduplicated articles were selected for further analysis; 14 studies were identified for critical review. All were series of cases and none was controlled. The outcomes in 210 patients were assessed and expressed as the percentage of patients that improved with the procedure. Results A good response to MCS (pain relief > or = 40-50%) was observed in approximately 55% of patients who underwent surgery and in 45% of the 152 patients with a postoperative follow-up > or = 1 year. Visual analog scale scores were provided in 76 patients, revealing an average 57% improvement in the 41 responders. A good response was achieved in 54% of the 117 patients with central pain and 68% of the 44 patients with trigeminal neuropathic pain. Adverse effects were reported in 10 studies, including 157 patients. Infections (5.7%) and hardware-related problems (5.1%) were relatively common complications. Seizures occurred in 19 patients (12%) in the early postoperative period, but no chronic epilepsy was reported. Conclusions The results of the authors' review of the literature suggest that MCS is safe and effective in the treatment of chronic neuropathic pain. Results must be considered with caution, however, as none of the trials were blinded or controlled. Studies with a better design are mandatory to confirm the efficacy of MCS for chronic neuropathic pain.     

Validation and the future of stimulation therapy of the primary motor cortex

The use of electrical motor cortex stimulation (EMCS) for post-stroke pain was established in Japan and has spread globally. EMCS has been used for the treatment of neuropathic pain, Parkinson's syndrome, and recovery of motor paresis. Since 2000, repetitive transcranial magnetic stimulation (rTMS) has been developed for the treatment of various neurological disorders. rTMS is a non-invasive method with almost no adverse effects. In the USA, rTMS of the left dorsolateral prefrontal cortex was approved for the treatment of major depression in 2008. rTMS of the primary motor cortex (M1) has been studied worldwide for the treatment of neuropathic pain, Parkinson's disease, motor paresis after stroke, and other neurological problems. New methods and devices for rTMS therapy are under development, and rTMS of the M1 is likely to be established as an effective therapy for some neurological disorders. The present review discusses EMCS and rTMS of the M1 concisely.     

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.     

Recording of corticospinal evoked potential for optimum placement of motor cortex stimulation electrodes in the treatment of post-stroke pain

The corticospinal motor evoked potential (MEP) evoked by motor cortex stimulation was investigated as an intraoperative index for the placement of stimulation electrodes in the epidural space over the motor cortex for the treatment of post-stroke pain. A grid of plate electrodes was placed in the epidural space to cover the motor cortex, sensory cortex, and premotor cortex employing a magnetic resonance imaging-guided neuronavigation system in two patients with severe post-stroke pain in the right extremities, a 66-year-old man with dysesthesia manifesting as burning and aching sensation, and a 67-year-old woman with dysesthesia manifesting as pricking sensation. The D-wave of the corticospinal MEP was recorded with a flexible wire electrode placed in the epidural space of the spinal cord during anodal monopolar stimulation of each plate electrode under general anesthesia. The grid electrode was fixed in position with dural sutures and the craniotomy closed. The effect of pain reduction induced by anodal monopolar stimulation of the same plate electrodes was examined using the visual analogue scale (VAS) on a separate day in the awake state without anesthesia. Comparison of the percentage VAS reduction and the recorded amplitude of the D-wave employing the same stimulation electrode revealed significant correlations in Case 1 (r = 0.828, p < 0.01) and Case 2 (r = 0.807, p < 0.01). The grid electrode was then replaced with two RESUME electrodes over the hand and foot areas, and the optimum positions were identified by D-wave recording before electrode fixation. Both patients reported satisfactory pain alleviation with lower stimulation voltages than usually required for patients with similar symptoms. These results indicate the potential of D-wave recording as an intraoperative indicator for the placement of stimulating electrodes over the motor cortex for pain relief.     

Tumour-surgery within the central motor strip: Surgical results with the aid of electrical motor cortex stimulation

Summary Surgery of tumours within or close to the central motor area always carries the risk of a new or increased postoperative motor deficit. One reason may be the difficulty of localizing the sensorimotor region, when it is displaced or distorted by the tumour and the perifocal oedema. Recently anatomical data of the craniocerebral topography of the central sulcus^{6, 9, 15} became available. We safely used under general anaesthesia the intraoperative mapping of the motor cortex by direct cortical electrical stimulation. In 21 patients tumours adjacent to or within the motor area were microsurgically resected. As a result of intraoperative localization the surgical approach had to be modified in contrast to the preoperative localization of the lesion in 5 patients. No new or increased motor deficit occurred and in some cases the preoperative weakness was reduced remarkably.     

A larynx area in the human motor cortex

The map of the human motor cortex has lacked a representation for the intrinsic musculature of the larynx ever since the electrical stimulation studies of Penfield. In addition, there has been no attempt to localize this area using neuroimaging techniques. Because of the central importance of laryngeal function to vocalization, we sought to localize an area controlling the intrinsic muscles of the larynx by using functional magnetic resonance imaging and to place this area in a somatotopic context. We had subjects perform a series of oral tasks designed to isolate elementary components of phonation and articulation, including vocalization of a vowel, lip movement, and tongue movement. In addition, and for the first time in a neuroimaging study, we had subjects perform "glottal stops," in other words forced closure of the glottis in the absence of vocalizing. The results demonstrated a larynx-specific area in the motor cortex that is activated comparably by vocal and nonvocal laryngeal tasks. Converging evidence suggests that this area is the principal vocal center of the human motor cortex. Finally, the location of this larynx area is strikingly different from that reported in the monkey. We discuss the implications of this observation for the evolution of vocal communication in humans.     

Motor cortex stimulation for central and peripheral deafferentation pain. Report of eight cases

The authors tested a modified motor cortex stimulation protocol for treatment of central and peripheral types of deafferentation pain. Four patients with thalamic pain and four with peripheral deafferentation pain were studied. Preoperative pharmacological tests of pain relief were performed using phentolamine, lidocaine, ketamine, thiopental, and placebo. In five patients we placed a 20- or 40-electrode grid in the subdural space to determine the best stimulation point for pain relief for a few weeks before definitive placement of a four-electrode array. In three patients, the four-electrode array was implanted in the interhemispheric fissure as a one-stage procedure to treat lower-extremity pain. In two patients with pain extending from the extremity to the trunk or hip, dual devices were implanted to drive two electrodes. Six of eight patients experienced pain reduction (two each with excellent, good, and fair relief) from motor cortex stimulation. No correlation was apparent between pharmacological test results and the effectiveness of motor cortex stimulation. Patients with peripheral deafferentation pain, including two with phantom-limb pain and two with brachial plexus injury, attained pain relief from motor cortex stimulation, with excellent results in two cases. Testing performed with a subdural multiple-electrode grid was helpful in locating the best stimulation point for pain relief. Motor cortex stimulation may be effective for treating peripheral as well as central deafferentation pain.     

Motor cortex stimulation for post-stroke pain using neuronavigation and evoked potentials: report of 3 cases

Although motor cortex stimulation (MCS) has been accepted as an effective therapeutic option for central pain, the efficacy of MCS widely varies among previous reports. In this report, we describe our recent trial for successful MCS in 3 patients with central pain due to cerebral stroke. Medical treatments were transiently effective, but gradually became ineffective in all of the cases. During surgery, the appropriate cortical target was determined by using neuronavigation, somatosensory evoked potential (SEP), and motor evoked potential (MEP). A flat, four-plate electrode was positioned on the dura mater parallel to the motor cortex. After surgery, pain almost resolved in 2 of 3 patients and markedly improved in another. The pain relief depended on their motor function. These findings strongly suggest that both patient selection and intraoperative monitoring for targeting the motor cortex are quite important for successful MCS, although further studies were essential.     

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.     

Predicting the location of mouth motor cortex in patients with brain tumors by using somatosensory evoked field measurements

OBJECT: Before resective brain surgery, localization of the functional regions is necessary to minimize postoperative deficits. The face area has been relatively difficult to map noninvasively by using functional imaging techniques. Preoperative localization of face somatosensory cortex with magnetoencephalography (MEG) may allow the surgeon to predict the location of mouth motor areas. METHODS: The authors compared the location of face somatosensory cortex obtained with somatosensory evoked fields during preoperative MEG with the mouth motor areas identified during intraoperative electrocortical stimulation (ECS) mapping in 13 patients undergoing resection of brain tumor. RESULTS: In this group of patients, ECS mouth motor sites were usually anterior and lateral to MEG localizations of lip somatosensory cortex. The consistent quantitative relationship between results of these two mapping procedures allows the practitioner to predict the location of mouth motor cortex based on noninvasive preoperative MEG measurements. CONCLUSIONS: Based on this result, the authors suggest that somatosensory mapping using MEG can be used to guide intraoperative mapping and neurosurgical planning.     

Recovery of pain control by intensive reprogramming after loss of benefit from motor cortex stimulation for neuropathic pain

INTRODUCTION: Motor cortex stimulation (MCS) may serve as an adjunct in managing neuropathic pain after other conservative and interventional methods have failed. However, the magnitude and duration of the benefit are highly variable, with a significant percentage of patients losing pain relief over time. We investigated whether intensive reprogramming could recapture the beneficial effects of MCS. METHODS: Six patients who had previously undergone MCS implantation for neuropathic pain but had lost benefit were brought back for 1-5 days of intensive reprogramming. Four patients were evaluated as inpatients while the others were seen as outpatients during multiple visits over several days. Several hours a day were spent with each patient. Patients completed visual analog scale (VAS) ratings at intervals throughout the reprogramming period to judge effectiveness of stimulation. Pre- and postadjustment VAS were compared using a paired t test. RESULTS: The patients' average age was 50 years (range 26-71). The diagnoses were trigeminal neuropathic pain (2 patients), complex regional pain syndrome I (2), phantom limb pain (1) and poststroke pain (1). The mean duration of pain was 6 years. The MCS benefit had initially lasted for a mean of 7.16 months (range 2-18 months). After reprogramming, 5 of 6 patients experienced improvement in pain. Average VAS scores decreased from 7.44 to 2.28 (p < 0.001) in those patients who responded to reprogramming. The average stimulation parameters in these patients were 5 V amplitude (range 1.7-10), 313 micros pulse width (range 240-390) and frequency of 84 Hz (range 55-130). Three patients experienced seizures during reprogramming. The mean seizure threshold was 8.9 V. No patient experienced seizures at their therapeutic settings. Pain control has been maintained after discharge. CONCLUSION: Intensive reprogramming can recapture the benefit of MCS in patients who have lost pain control. The use of broad dipoles using two contacts rather than one contact of the 1 x 4 electrode array improved the ability to recapture beneficial stimulation. There is a significant risk of seizures during aggressive reprogramming.     

Functional magnetic resonance imaging is more reliable than somatosensory evoked potential or mapping for the detection of the primary motor cortex in proximity to a tumor

The accurate localization of the primary motor cortex (M1) is critical for the preservation of motor function during resection of brain tumors in and around the M1. The goal of the present study was to determine which technique provided the most accurate localization of M1. The accuracy of preoperative functional magnetic resonance imaging (fMRI), intraoperative somatosensory evoked potential (SEP) and cortical mapping for the localization of M1 was determined in 17 patients with brain tumors in and around the M1. Because localization of the M1 is typically symmetrical in the cerebral hemispheres, the M1 on the affected side was localized by determination of the M1 location on the unaffected side using fMRI with patient hand clenching. The location of M1 was successfully determined by SEP in 5 of 11 cases. In the remainder of cases, the sulcus at which phase reversal occurred during SEP was shifted 1 or 2 gyri rostral to the central sulcus. The location of M1 was successfully determined by brain mapping in 9 of 15 cases. In the remainder of cases, stimulation failed to elicit a motor response. Finally, the location of M1 was successfully determined by fMRI in 16 of 17 cases. These data indicate that fMRI was more reliable than SEP or brain mapping for the detection of M1 in proximity to a tumor.     

Precentral cortex stimulation for the treatment of central neuropathic pain: results of a prospective study in a 20-patient series

The authors report a series of 23 patients with central neuropathic pain who were treated with the recently developed technique of precentral cortex stimulation (PCS). Of the 20 patients with a follow-up of more than 1 year (mean of 23 months) 25% had an excellent, 35% a good and 15% a fair relief of pain. In 25% the method failed. On the basis of these findings and the literature data (127 reported cases), the authors advocate PCS in patients with severe and medically refractory poststroke pain.     

Reversal of thalamic hand syndrome by long-term motor cortex stimulation

The authors describe a case of complete recovery from the so-called "thalamic hand" syndrome following chronic motor cortex stimulation in a 64-year-old man suffering from poststroke thalamic central pain. As of the 2-year follow-up examination, the patient's dystonia and pain are still controlled by electrical stimulation. It is speculated that a common mechanism in which the thalamocortical circuit loops are rendered out of balance may sustain hand dystonia and central pain in this case of thalamic syndrome. To the authors' knowledge this is the first reported case of its kind.     

Localization of human sensorimotor cortex during surgery by cortical surface recording of somatosensory evoked potentials

The traditional means of localizing sensorimotor cortex during surgery is Penfield's procedure of mapping sensory and motor responses elicited by electrical stimulation of the cortical surface. This procedure can accurately localize sensorimotor cortex but is time-consuming and best carried out in awake, cooperative patients. An alternative localization procedure is presented that involves cortical surface recordings of somatosensory evoked potentials (SEP's), providing accurate and rapid localization in patients under either local or general anesthesia. The morphology and amplitude of median nerve SEP's recorded from the cortical surface varied systematically as a function of spatial location relative to the sensorimotor hand representation area. These results were validated in 18 patients operated on under local anesthesia in whom the sensorimotor cortex was independently localized by electrical stimulation mapping; the two procedures were in agreement in all cases. Similar SEP results were demonstrated in an additional 27 patients operated on under general anesthesia without electrical stimulation mapping. The following three spatial relationships between SEP's and the anatomy of the sensorimotor cortex permit rapid and accurate localization of the sensorimotor hand area: 1) SEP's with approximately mirror-image waveforms are recorded at electrode sites in the hand area on opposite sides of the central sulcus (P20-N30 precentrally and N20-P30 postcentrally); 2) the P25-N35 is recorded from the postcentral gyrus as well as a small region of the precentral gyrus in the immediate vicinity of the central sulcus: this waveform is largest on the postcentral gyrus about 1 cm medial to the focus of the 20- and 30-msec potentials; and 3) regardless of component identification, maximum SEP amplitudes are recorded from the hand representation area on the precentral and postcentral gyri.