Curr Pain Headache Rep (2014) 18:427 DOI 10.1007/s11916-014-0427-2
NEUROMODULATION (M GOFELD, SECTION EDITOR)
Deep Brain and Motor Cortex Stimulation Vishad V. Sukul & Konstantin V. Slavin
Published online: 10 May 2014 # Springer Science+Business Media New York 2014
Abstract Deep brain stimulation (DBS) and motor cortex stimulation (MCS) are established surgical modalities that have been successfully used over the last several decades for treatment of numerous chronic pain disorders. Most often, these approaches are reserved for severe, disabling, and medically refractory syndromes after less invasive approaches have been tried and have failed. Although the exact mechanism of action for DBS and MCS remains unknown, it appears that these central neuromodulation processes have multifactorial effects on central pain processing and descending pain inhibition. Clinical studies and laboratory reports have shed some light on stimulation details and optimal parameters, as well as the choice of stimulation targets, best surgical indications, and expected long-term outcomes. Based on the worldwide published experience, it appears that additional data is needed to obtain regulatory approval for both MCS and DBS for the treatment of pain. Following approval, further clinical research will shape the ability to initiate, implement, and update comprehensive patient and procedure selection paradigms.
Keywords Neuropathic pain . Nociceptive pain . Post-stroke pain . Spinal cord injury . Brachial plexus avulsion . Deafferentation . Post-amputation pain . Electrical neurostimulation This article is part of the Topical Collection on Neuromodulation V. V. Sukul Department of Neurosurgery, Temple University, Philadelphia, PA 19140, USA e-mail: [email protected] K. V. Slavin (*) Department of Neurosurgery, University of Illinois at Chicago, 912 South Wood Street (MC 799), Chicago, IL 60612, USA e-mail: [email protected]
Introduction Over the past several decades, electrical neuromodulation has been proven clinically effective in the treatment of various socalled functional neurological disorders (i.e., movement disorders and epilepsy). Neuromodulation techniques have been introduced within functional neurological surgery in multiple complex conditions such as psychiatric disorders and chronic pain. Deep brain stimulation (DBS) and motor cortex stimulation (MCS) have shown particular promise in the treatment of various chronic pain syndromes, including neuropathic p a i n , e ff e c t i v e l y c o m p l e t i n g t h e c o n t i n u u m o f neurostimulation that starts at the periphery (as in peripheral nerve field stimulation and peripheral nerve stimulation) and ends in cerebral centers that participate in pain processing. With the wide spectra of other neuromodulation techniques for pain, such as spinal cord stimulation, the goal of understanding cerebral pain pathways and how they are affected by neuromodulation becomes increasingly important. This article reviews the current targets and therapeutic options for chronic pain with regard to both DBS and MCS.
Deep Brain Stimulation DBS modulation of pain utilizes a surgical approach that is similar, if not identical, to that of DBS for movement disorders. The surgery is performed in two parts. Initially, a stereotactic frame is applied under local anesthesia, and highresolution imaging (MRI, CT, or both) is performed to allow for the calculation of target coordinates based on imaging findings, known landmarks, and stereotactic atlas coordinates. Some centers have adopted frameless stereotaxis for these procedures, but most facilities continue to use frame-based methods.
427, Page 2 of 5
Following calculation of the coordinates, the surgical procedure commences with attachment of the surgical instruments (stereotactic arc, microdrive, and other accessories) to the head frame. Initial targeting includes selection of an entry point into the brain. An appropriate skin incision is made to create a burr hole in standard pre-coronal location. The trajectory between the entry point and the target is chosen to avoid both blood vessels and the ventricles. Some surgeons employ microelectrode recording to verify the nature of deep cerebral structures, but the mandatory part of surgery – and the main reason this stage of surgery is done with the patient awake – is the physiologic confirmation of the target via macrostimulation. The main goal of this stage of surgery is to evaluate thresholds and side effects of stimulation. Upon completion of the testing, the DBS electrode is inserted into the desired target and appropriately secured in place. An implantable pulse generator may be placed in the same sitting or at a later date during second stage of DBS surgery. In case of staging the implant, some centers prefer dong a short stimulation trial (1-2 weeks) with an externalized extension cable to determine DBS efficacy [1•, 2]. Targets for Pain The efficacy of DBS for any indication, whether chronic pain or movement disorders, greatly depends upon the choice of stimulation target. Historically, both lesioning and stimulation of the thalamic, hypothalamic, and brainstem structures were considered and attempted for alleviation of various chronic pain syndromes [3]. Over the years, surgeons who have performed DBS for pain have found the greatest efficacy in very specific etiologies, such as central post-stroke pain (CPSP), atypical facial pain, anesthesia dolorosa, spinal pain, brachial plexus injury, and some cases of phantom limb pain [1•, 2, 4]. As always, thorough diagnostic workup and failure of medical treatment by a pain management team are necessary before considering DBS. Over the past three decades, common targets have included the periaqueductal gray area (PAG)/periventricular gray area (PVG) and the sensory (ventro-caudate) thalamus (VC) [5, 6]. A 1995 meta-analysis of studies on DBS for chronic pain showed impressive early success with PAG/PVG stimulation for nociceptive pain syndromes (67 % long-term success), and thalamic stimulation in the VC has shown considerable promise in patients with neuropathic pain syndromes [1•]. In the past, it was theorized that the mechanism of PAG/PVG DBSinduced analgesia was related to the release of endogenous opioids, a theory that was somewhat supported by reversal of PAG DBS analgesia with naloxone [7]. Because the analgesic effect and underlying mechanisms are likely multifactorial, ascending pathways within the PVG may be involved as well. The mechanism of VC stimulation is also not fully understood, although it is likely related to activation of inhibitory
Curr Pain Headache Rep (2014) 18:427
corticofugal fibers. VC is implicated in pain localization, and there is some evidence that bursting and lateral spread to other nuclei can result in conscious perception related to aberrant pain signals. Indeed, an improved understanding of pain pathways and the shifting opinion toward neuromatrix versus gatecontrol theory of pain are allowing for innovative testing of deep subcortical targets [6, 7]. There has been a flurry of scientific research within the past several years that has taken a closer look at these well-known targets and has shed some light on possible new targets for various indications. A 2012 prospective cohort study reviewed approximately 200 patients referred for DBS trial (85 received DBS, 59 with full implantation) for a variety of neuropathic pain etiologies, including spinal pathology, poststroke pain, facial pain, and brachial plexus injury [8••]. Primary targets were the contralateral PVG, parts of VC (ventral posterolateral and ventral posteromedial [VPL and VP]) nuclei), and, in over 40 % of patients, both targets. The study found that success rate varied by pain etiology, from 50 % in brachial plexus injuries to almost 90 % in postamputation pain syndromes. Sixty-six percent of all patients had a global improvement in EQ-5D health state, and within this cohort there was a 50 % improvement in VAS over the one-year post-implantation period. Based upon their experience, the authors suggested stimulation of the PVG first, and if that fails, falling back on VPL/VPM stimulation. Unfortunately, they noted a continued problem with DBS for pain: approximately one-fourth of patients with a successful trial did not experience long-term relief after full implantation. This may have been for a variety of reasons, including development of stimulation tolerance and patient dropout [8••]. The same group from the UK reported on a two-year follow-up of VPL DBS for amputation- or brachial plexus avulsion (BPA)-induced neuropathic pain. Eleven patients treated with DBS over 29 months demonstrated statistically significant (p
NEUROMODULATION (M GOFELD, SECTION EDITOR)
Deep Brain and Motor Cortex Stimulation Vishad V. Sukul & Konstantin V. Slavin
Published online: 10 May 2014 # Springer Science+Business Media New York 2014
Abstract Deep brain stimulation (DBS) and motor cortex stimulation (MCS) are established surgical modalities that have been successfully used over the last several decades for treatment of numerous chronic pain disorders. Most often, these approaches are reserved for severe, disabling, and medically refractory syndromes after less invasive approaches have been tried and have failed. Although the exact mechanism of action for DBS and MCS remains unknown, it appears that these central neuromodulation processes have multifactorial effects on central pain processing and descending pain inhibition. Clinical studies and laboratory reports have shed some light on stimulation details and optimal parameters, as well as the choice of stimulation targets, best surgical indications, and expected long-term outcomes. Based on the worldwide published experience, it appears that additional data is needed to obtain regulatory approval for both MCS and DBS for the treatment of pain. Following approval, further clinical research will shape the ability to initiate, implement, and update comprehensive patient and procedure selection paradigms.
Keywords Neuropathic pain . Nociceptive pain . Post-stroke pain . Spinal cord injury . Brachial plexus avulsion . Deafferentation . Post-amputation pain . Electrical neurostimulation This article is part of the Topical Collection on Neuromodulation V. V. Sukul Department of Neurosurgery, Temple University, Philadelphia, PA 19140, USA e-mail: [email protected] K. V. Slavin (*) Department of Neurosurgery, University of Illinois at Chicago, 912 South Wood Street (MC 799), Chicago, IL 60612, USA e-mail: [email protected]
Introduction Over the past several decades, electrical neuromodulation has been proven clinically effective in the treatment of various socalled functional neurological disorders (i.e., movement disorders and epilepsy). Neuromodulation techniques have been introduced within functional neurological surgery in multiple complex conditions such as psychiatric disorders and chronic pain. Deep brain stimulation (DBS) and motor cortex stimulation (MCS) have shown particular promise in the treatment of various chronic pain syndromes, including neuropathic p a i n , e ff e c t i v e l y c o m p l e t i n g t h e c o n t i n u u m o f neurostimulation that starts at the periphery (as in peripheral nerve field stimulation and peripheral nerve stimulation) and ends in cerebral centers that participate in pain processing. With the wide spectra of other neuromodulation techniques for pain, such as spinal cord stimulation, the goal of understanding cerebral pain pathways and how they are affected by neuromodulation becomes increasingly important. This article reviews the current targets and therapeutic options for chronic pain with regard to both DBS and MCS.
Deep Brain Stimulation DBS modulation of pain utilizes a surgical approach that is similar, if not identical, to that of DBS for movement disorders. The surgery is performed in two parts. Initially, a stereotactic frame is applied under local anesthesia, and highresolution imaging (MRI, CT, or both) is performed to allow for the calculation of target coordinates based on imaging findings, known landmarks, and stereotactic atlas coordinates. Some centers have adopted frameless stereotaxis for these procedures, but most facilities continue to use frame-based methods.
427, Page 2 of 5
Following calculation of the coordinates, the surgical procedure commences with attachment of the surgical instruments (stereotactic arc, microdrive, and other accessories) to the head frame. Initial targeting includes selection of an entry point into the brain. An appropriate skin incision is made to create a burr hole in standard pre-coronal location. The trajectory between the entry point and the target is chosen to avoid both blood vessels and the ventricles. Some surgeons employ microelectrode recording to verify the nature of deep cerebral structures, but the mandatory part of surgery – and the main reason this stage of surgery is done with the patient awake – is the physiologic confirmation of the target via macrostimulation. The main goal of this stage of surgery is to evaluate thresholds and side effects of stimulation. Upon completion of the testing, the DBS electrode is inserted into the desired target and appropriately secured in place. An implantable pulse generator may be placed in the same sitting or at a later date during second stage of DBS surgery. In case of staging the implant, some centers prefer dong a short stimulation trial (1-2 weeks) with an externalized extension cable to determine DBS efficacy [1•, 2]. Targets for Pain The efficacy of DBS for any indication, whether chronic pain or movement disorders, greatly depends upon the choice of stimulation target. Historically, both lesioning and stimulation of the thalamic, hypothalamic, and brainstem structures were considered and attempted for alleviation of various chronic pain syndromes [3]. Over the years, surgeons who have performed DBS for pain have found the greatest efficacy in very specific etiologies, such as central post-stroke pain (CPSP), atypical facial pain, anesthesia dolorosa, spinal pain, brachial plexus injury, and some cases of phantom limb pain [1•, 2, 4]. As always, thorough diagnostic workup and failure of medical treatment by a pain management team are necessary before considering DBS. Over the past three decades, common targets have included the periaqueductal gray area (PAG)/periventricular gray area (PVG) and the sensory (ventro-caudate) thalamus (VC) [5, 6]. A 1995 meta-analysis of studies on DBS for chronic pain showed impressive early success with PAG/PVG stimulation for nociceptive pain syndromes (67 % long-term success), and thalamic stimulation in the VC has shown considerable promise in patients with neuropathic pain syndromes [1•]. In the past, it was theorized that the mechanism of PAG/PVG DBSinduced analgesia was related to the release of endogenous opioids, a theory that was somewhat supported by reversal of PAG DBS analgesia with naloxone [7]. Because the analgesic effect and underlying mechanisms are likely multifactorial, ascending pathways within the PVG may be involved as well. The mechanism of VC stimulation is also not fully understood, although it is likely related to activation of inhibitory
Curr Pain Headache Rep (2014) 18:427
corticofugal fibers. VC is implicated in pain localization, and there is some evidence that bursting and lateral spread to other nuclei can result in conscious perception related to aberrant pain signals. Indeed, an improved understanding of pain pathways and the shifting opinion toward neuromatrix versus gatecontrol theory of pain are allowing for innovative testing of deep subcortical targets [6, 7]. There has been a flurry of scientific research within the past several years that has taken a closer look at these well-known targets and has shed some light on possible new targets for various indications. A 2012 prospective cohort study reviewed approximately 200 patients referred for DBS trial (85 received DBS, 59 with full implantation) for a variety of neuropathic pain etiologies, including spinal pathology, poststroke pain, facial pain, and brachial plexus injury [8••]. Primary targets were the contralateral PVG, parts of VC (ventral posterolateral and ventral posteromedial [VPL and VP]) nuclei), and, in over 40 % of patients, both targets. The study found that success rate varied by pain etiology, from 50 % in brachial plexus injuries to almost 90 % in postamputation pain syndromes. Sixty-six percent of all patients had a global improvement in EQ-5D health state, and within this cohort there was a 50 % improvement in VAS over the one-year post-implantation period. Based upon their experience, the authors suggested stimulation of the PVG first, and if that fails, falling back on VPL/VPM stimulation. Unfortunately, they noted a continued problem with DBS for pain: approximately one-fourth of patients with a successful trial did not experience long-term relief after full implantation. This may have been for a variety of reasons, including development of stimulation tolerance and patient dropout [8••]. The same group from the UK reported on a two-year follow-up of VPL DBS for amputation- or brachial plexus avulsion (BPA)-induced neuropathic pain. Eleven patients treated with DBS over 29 months demonstrated statistically significant (p
