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Neuropathic pain is a chronic condition lacking effective management and responding poorly to standard treatment protocols. Motor cortex stimulation has emerged as a new and promising therapeutic tool with outcomes potentially affected by the specific causes and location. In this study we report a series of eight cases in the neurosurgery practice of one of the authors (R.J.B.), including neuropathic pain syndromes of trigeminal or thalamic origin with or without anesthesia dolorosa. Pain relief was evaluated on the basis of comparison of Visual Analog scores at baseline and at 3 months after surgery. In addition, we assessed differences in pain relief outcomes between cases with trigeminal neuralgia and thalamic stroke, as well as cases with or without anesthesia dolorosa (i.e. pain with numbness of the affected area). Visual Analog Scale scores showed a statistically significant decrease of 4.19 (P=0.002) at 3 months follow-up compared with baseline. Pain relief levels in four of five patients in the subgroup with facial pain were higher than 50%, and none of the patients in the subgroup with thalamic and phantom limb pain showed such a good outcome. Furthermore, we found larger pain relief levels in facial pain conditions with versus without anesthesia dolorosa. These results point to utility of motor cortex stimulation in relieving neuropathic pain, as well as better outcomes for patients with facial pain and anesthesia dolorosa. Future studies should incorporate methods to noninvasively trial those patients who may benefit from surgical implantation to predict the outcomes and maximize their negative predictive value.
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PMID:Motor cortex stimulation for neuropathic pain syndromes: a case series experience. 2478 Aug 96

Refractory pain syndromes often have far reaching effects and are quite a challenge for primary care providers and specialists alike to treat. With the help of site-specific neuromodulation and appropriate patient selection these difficult to treat pain syndromes may be managed. In this article, we focus on supraspinal stimulation (SSS) for treatment of intractable pain and discuss off-label uses of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in context to emerging indications in neuromodulation. Consideration for neuromodulatory treatment begins with rigorous patient selection based on exhaustive conservative management, elimination of secondary gains, and a proper psychology evaluation. Trial stimulation prior to DBS is nearly always performed while trial stimulation prior to MCS surgery is symptom dependent. Overall, a review of the literature demonstrates that DBS should be considered for refractory conditions including nociceptive/neuropathic pain, phantom limb pain, and chronic cluster headache (CCH). MCS should be considered primarily for trigeminal neuropathic pain (TNP) and central pain. DBS outcome studies for post-stroke pain as well as MCS studies for complex regional pain syndrome (CRPS) show more modest results and are also discussed in detail.
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PMID:Supraspinal stimulation for treatment of refractory pain. 2495 45

Extended viewing of movements of one's intact limb in a mirror as well as motor imagery have been shown to decrease pain in persons with phantom limb pain or complex regional pain syndrome and to increase the movement ability in hemiparesis following stroke. In addition, mirrored movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. However, using a so-called mirror box has technical limitations, some of which can be overcome by virtual reality applications. We developed a virtual reality mirror box application and evaluated its comparability to a classical mirror box setup. We applied both paradigms to 20 healthy controls and analyzed vividness and authenticity of the illusion as well as brain activation patterns. In both conditions, subjects reported similar intensities for the sensation that movements of the virtual left hand felt as if they were executed by their own left hand. We found activation in the primary sensorimotor cortex contralateral to the actual movement, with stronger activation for the virtual reality 'mirror box' compared to the classical mirror box condition, as well as activation in the primary sensorimotor cortex contralateral to the mirrored/virtual movement. We conclude that a virtual reality application of the mirror box is viable and that it might be useful for future research.
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PMID:Illusion-related brain activations: a new virtual reality mirror box system for use during functional magnetic resonance imaging. 2544 53

Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.
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PMID:Deep brain stimulation for chronic pain. 2612 83

Background and purpose This case of a 42 year old woman with lower extremity Complex Regional Pain Syndrome (CRPS) after a twisting injury of the ankle, effectively treated with the addition of mirror therapy to a rehabilitation programme, prompted a literature review of both CRPS and mirror therapy. Mirror therapy is a newer adjunct to other forms of pain control and functional restoration for treatment of CRPS as well as other difficult clinical problems. This was a required group project as part of a university based course in chronic pain for healthcare workers. Materials and methods The PubMed database up to September 26,2012 was reviewed using four search word groups: "CRPS mirror therapy", "mirror CRPS", "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror" and "reflex sympathetic dystrophy OR Complex Regional Pain Syndrome AND mirror + RCT". Nine studies from PubMed met the criteria that this working group had chosen for inclusion in the analysis of mirror therapy as treatment. These references were supplemented by others on CRPS in order to generate an adequate review of both the syndrome CRPS and mirror therapy itself. Some references were specific for mirror therapy in the treatment of CRPS but others described mirror therapy for the treatment of phantom limb pain, brachial plexus avulsion pain, for physical rehabilitation of stroke related paresis and for rehabilitation after hand surgery. Results Criteria for the diagnosis of CRPS including the International Association for the Study of Pain criteria and the Budapest criteria are reviewed with an emphasis on the specificity and sensitivity of the various criteria for clinical and research purposes. The signs and symptoms of CRPS are a part of the criteria review. The main treatment strategy for CRPS is physical rehabilitation for return of function and mirror therapy is one of many possible strategies to aid in this goal. The patient in this case report had failed many of the adjunctive therapies and rehabilitation had been unsuccessful until the addition of mirror therapy. She then could progress with physical rehabilitation and return to a more normal life. Mirror therapy techniques are briefly described as part of a discussion of its success with relationship to signs and symptoms as well as to the duration of CRPS (and other syndromes). Some discussion of the theories of the central effects of both CRPS and phantom limb pain and how these are affected by mirror therapy is included. An analysis of the 9 most relevant articles plus a critique of each is present in table form for review. Conclusions There appears to be a clear indication for the use of mirror therapy to be included in the multidisciplinary treatment of CRPS types 1 and 2 with a positive effect on both pain and motor function. There is also evidence that mirror therapy can be helpful in other painful conditions such as post stroke pain and phantom limb pain. Implications CRPS is often overlooked as an explanation for obscure pain problems. Prompt diagnosis is essential for effective treatment. Mirror therapy is a newer technique, easy to perform and can be a useful adjunct to aid physical rehabilitation and decrease pain in this population. Much further prospective research on mirror therapy in CRPS is ongoing and is needed to systematize the technique, to clarify the effects and to define the place of this therapy in the multidisciplinary management of CRPS.
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PMID:Mirror therapy for Complex Regional Pain Syndrome (CRPS)-A literature review and an illustrative case report. 2991 36

Background: Motor cortex stimulation (MCS) is an intracranial, invasive method for treatment of chronic pain. Main indications for MCS are central post stroke pain, neuropathic facial pain, phantom limb pain and brachial plexus or spinal cord injury pain. Spinal cord stimulation (SCS) with burst waveform has been proved to be more effective than tonic mode in chronic pain. Necessity to replace depleted batteries of motor cortex tonic stimulators gave us an opportunity of applying burst stimulation. The objective of the pilot study was to evaluate the effects of burst stimulation applied on motor cortex in patients with chronic pain syndromes as well as comparison to tonic mode. Materials and methods: We have evaluated 6 patients (females N=3, males N=3) belonging to the group of 14 cases (females N=5, males N=9) who had undergone surgical procedure of MCS in years 2005-2017. Selected for the study were 6 patients with thalamic pain N=3, with facial pain N=3 (anaesthesia dolorosa and neuropathic trigeminal neuralgia). The patients were subjected to both modes of stimulation then they chose which one was better in relieving pain: tonic or burst. Pain intensity was assessed with the visual analogue scale (VAS) before the replacement of implanted pulse generator (IPG) and after the stimulation with tonic and burst modes. Results: In the study, 5 out of 6 patients with MCS found burst mode more effective than tonic mode. Baseline VAS score in patients that had at least 3 months depleted battery of tonic IPG was 95 mm. After implantation of a new IPG mean VAS score on tonic stimulation was 72 mm, on burst 53 mm. Conclusions: The most preferred option of MCS in selected group of patients was burst stimulation. This study has shown, that the burst stimulation of cerebral cortex is a promising modality when tonic stimulation is not sufficient in refractory, neuropathic pain.
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PMID:Effectiveness of tonic and burst motor cortex stimulation in chronic neuropathic pain. 3202 8

Real-time functional magnetic resonance imaging (fMRI) is a promising non-invasive method for brain-computer interfaces (BCIs). BCIs translate brain activity into signals that allow communication with the outside world. Visual and motor imagery are often used as information-encoding strategies, but can be challenging if not grounded in recent experience in these modalities, e.g., in patients with locked-in-syndrome (LIS). In contrast, somatosensory imagery might constitute a more suitable information-encoding strategy as the somatosensory function is often very robust. Somatosensory imagery has been shown to activate the somatotopic cortex, but it has been unclear so far whether it can be reliably detected on a single-trial level and successfully classified according to specific somatosensory imagery content. Using ultra-high field 7-T fMRI, we show reliable and high-accuracy single-trial decoding of left-foot (LF) vs. right-hand (RH) somatosensory imagery. Correspondingly, higher decoding accuracies were associated with greater spatial separation of hand and foot decoding-weight patterns in the primary somatosensory cortex (S1). Exploiting these novel neuroscientific insights, we developed-and provide a proof of concept for-basic BCI communication by showing that binary (yes/no) answers encoded by somatosensory imagery can be decoded with high accuracy in simulated real-time (in 7 subjects) as well as in real-time (1 subject). This study demonstrates that body part-specific somatosensory imagery differentially activates somatosensory cortex in a topographically specific manner; evidence which was surprisingly still lacking in the literature. It also offers proof of concept for a novel somatosensory imagery-based fMRI-BCI control strategy, with particularly high potential for visually and motor-impaired patients. The strategy could also be transferred to lower MRI field strengths and to mobile functional near-infrared spectroscopy. Finally, given that communication BCIs provide the BCI user with a form of feedback based on their brain signals and can thus be considered as a specific form of neurofeedback, and that repeated use of a BCI has been shown to enhance underlying representations, we expect that the current BCI could also offer an interesting new approach for somatosensory rehabilitation training in the context of stroke and phantom limb pain.
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PMID:Topographic Somatosensory Imagery for Real-Time fMRI Brain-Computer Interfacing. 3192 May 88

This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease. We start with the concept that brain function can be understood only by understanding its networks, how and why information flows in the brain. The first manuscript dealt with methods for network analysis, and the current manuscript focuses on the use of these methods to understand a wide variety of neurological and psychiatric disorders. Disorders considered are neurodegenerative disorders, such as Alzheimer disease and amyotrophic lateral sclerosis, stroke, movement disorders, including essential tremor, Parkinson disease, dystonia and apraxia, epilepsy, psychiatric disorders such as schizophrenia, and phantom limb pain. This state-of-the-art review makes clear the value of networks and brain models for understanding symptoms and signs of disease and can serve as a foundation for further work.
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PMID:Human brain connectivity: Clinical applications for clinical neurophysiology. 3241 3

Injury induces synaptic, circuit, and systems reorganization. After unilateral amputation or stroke, this functional loss disrupts the interhemispheric interaction between intact and deprived somatomotor cortices to recruit deprived cortex in response to intact limb stimulation. This recruitment has been implicated in enhanced intact sensory function. In other patients, maladaptive consequences such as phantom limb pain can occur. We used unilateral whisker denervation in male and female mice to detect circuitry alterations underlying interhemispheric cortical reorganization. Enhanced synaptic strength from the intact cortex via the corpus callosum (CC) onto deep neurons in deprived primary somatosensory barrel cortex (S1BC) has previously been detected. It was hypothesized that specificity in this plasticity may depend on to which area these neurons projected. Increased connectivity to somatomotor areas such as contralateral S1BC, primary motor cortex (M1) and secondary somatosensory cortex (S2) may underlie beneficial adaptations, while increased connectivity to pain areas like anterior cingulate cortex (ACC) might underlie maladaptive pain phenotypes. Neurons from the deprived S1BC that project to intact S1BC were hyperexcitable, had stronger responses and reduced inhibitory input to CC stimulation. M1-projecting neurons also showed increases in excitability and CC input strength that was offset with enhanced inhibition. S2 and ACC-projecting neurons showed no changes in excitability or CC input. These results demonstrate that subgroups of output neurons undergo dramatic and specific plasticity after peripheral injury. The changes in S1BC-projecting neurons likely underlie enhanced reciprocal connectivity of S1BC after unilateral deprivation consistent with the model that interhemispheric takeover supports intact whisker processing.SIGNIFICANCE STATEMENT Amputation, peripheral injury, and stroke patients experience widespread alterations in neural activity after sensory loss. A hallmark of this reorganization is the recruitment of deprived cortical space which likely aids processing and thus enhances performance on intact sensory systems. Conversely, this recruitment of deprived cortical space has been hypothesized to underlie phenotypes like phantom limb pain and hinder recovery. A mouse model of unilateral denervation detected remarkable specificity in alterations in the somatomotor circuit. These changes underlie increased reciprocal connectivity between intact and deprived cortical hemispheres. This increased connectivity may help explain the enhanced intact sensory processing detected in humans.
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PMID:Circuit-Specific Plasticity of Callosal Inputs Underlies Cortical Takeover. 3291 9


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