NEUROENGINEERING - PART 3 pot

4 -6 Neuroengineering to the patient’s skull. Carbon fiber posts and MRI/CT-compatible pins are used. The MRI scan consists of a contrast-enhanced T1-weighted volume acquisition using axial 1.3-mm slices with zero slice-gap. This is followed by a whole-head CT scan using 3-mm slices with zero slice-gap. The two data sets are imported over the local network to a computer workstation (BrainLab, Heimstetten, Germany). After fusing MR and CT data, both target and trajectory are defined. A probe view algorithm is used to maximize the distance between any surface veins and the depth lead at the cortical entry point. At this point, the patient is appropriately positioned on the operating table by attaching the base- ring to the Mayfield holder. The craniotomy incision is marked with gentian violet, and the surgical area is prepped and draped in a standard sterile fashion. The previously marked incision is now infiltrated with a local anesthetic and a horseshoe-shaped craniotomy flap is turned. The Leksell stereotactic arc system is attached to the base-ring, and a drill guide tube is then advanced through the incision down to the skull and antibiotic irrigation is flushed through the tube. The appropriate burr hole is outlined on the skull and a high-speed, air-driven drill (Midas Rex, Fort Worth, TX) is used. Attention must be given to the diameter of the burr hole to exactly match the diameter of the Navigus (Image-guided Neurologics, Melbourne, FL) securing device, which will be used for securing the implanted depth lead (Figure 4.3). The underlying dura is opened in a linear fashion. At this point, a 2.1 mm inner-diameter guide block is introduced and the dura and pia are cauterized with a mono- polar electrode (AdTech, Racine, WI). Next, a 14-gauge depth electrode cannula (AdTech, Racine, WI) is passed through the same guide block to the target point. Intraoperative fluoroscopy is used to verify proper placement. The cannula and guide tube are then withdrawn. A Navigus cranial base and cap device is then implanted over the burr hole and secured by using the two self-tapping screws provided. Attention must be paid to align the exit groove on the base in the postero-lateral direction, in the same direction that the subcutaneous portion of the lead will later be directed. An insertion tool (AdTech, Racine, WI) is then passed through a large diameter guide block and inserted into the slot and the Navigus device. The insertion tool and guide block are then removed. The depth lead is then carefully inserted to the target point. Fluoroscopy is used again to verify proper position of the FIGURE 4.3 Intraoperative picture demonstrating the implanted Navigus electrode lead securing device (Image-guided Neurologics, Melbourne, FL) in its final position. 8174_C004.fm Page 6 Saturday, November 3, 2007 7:40 AM Responsive Neurostimulation for Epilepsy — Neurosurgical Experience 4 -7 implanted lead. The stylet of the lead is removed and the distal shaft of the implanted lead is secured into the Navigus device. 4.3.2.3 Subdural Lead Placement If a subdural strip lead is to be placed, the dura is opened linearly and the 1 × 4 cortical lead is inserted through the dural opening. Fluoroscopy is used to verify proper placement. The distal shaft of the implanted lead is safely secured to the Navigus device. 4.3.2.4 Pulse Generator Implantation At this point, the provided ferrule is placed on the exposed bone and the desired bony defect is outlined (Figure 4.4). The outlined bone is drilled out by a high-speed, air-driven drill with attention not to traumatize the underlying dura (Figure 4.5). The bony edges are smoothed and meticulous hemostasis is performed if necessary by applying bone wax. Thorough irrigation of the wound is of great importance for removing any residual bone dust. The provided ferrule is then implanted and secured to the adjacent bone at four points with the provided self-tapping mini-screws (Figure 4.2). The pulse generator is connected to the distal end of the already implanted lead or leads, and then is secured in the implanted ferrule (Figure 4.6). At this point, the programmer is used with the sterile covered telemetry wand to interrogate the implanted pulse generator, measure the impedances of all lead contacts, and perform electrocorticography to verify proper function of the implanted RNS ™ neurostimulator system. The surgical wound is thoroughly irrigated with bacitracin solution and then is closed in anatomical layers. The wound is covered with a sterile dressing. The patient is transported to the neurosurgical ward for observation and discharged within two to three days. Before discharge, a postoperative head CT scan and skull plain x-rays (antero-posterior and lateral views) are obtained to provide baseline imaging studies for future reference (Figures 4.7A and 4.7B). The first interrogation and seizure detection programming session is usually performed on the third postoperative day. Further interrogations and programming sessions are usually required for fine adjustment of the implanted RNS ™ neurostimulator detection and stimulation parameters. FIGURE 4.4 Intraoperative picture demonstrating the outlining of the pulse generator on the bone. 8174_C004.fm Page 7 Saturday, November 3, 2007 7:40 AM 4 -8 Neuroengineering FIGURE 4.5 Intraoperative picture demonstrating the bony defect created for implanting the ferrule and the pulse generator. FIGURE 4.6 (See color insert following page 15-4). Intraoperative picture demonstrating the pulse generator connected to an implanted depth lead and secured to the underlying ferrule. 8174_C004.fm Page 8 Saturday, November 3, 2007 7:40 AM Responsive Neurostimulation for Epilepsy — Neurosurgical Experience 4 -9 A B FIGURE 4.7 (A) Postoperative x-rays (lateral view) of one of our patients demonstrating the implanted RNS system with two subdural leads. (B) Postoperative x-rays (lateral view) of one of our patients demonstrating the implanted RNS system with two depth leads. 8174_C004.fm Page 9 Saturday, November 3, 2007 7:40 AM 4 -10 Neuroengineering The operative blood loss is usually minimal (in all of our cases has been maintained at less than 100 cc) while the mean duration of our surgical procedure of implantation is 3.2 hours (range 2 to 4.5 hours). 4.4 Conclusions The implantable, local, closed-loop RNS ™ neurostimulator system is an investigational option in patients with well-localized, focal, medically refractory epilepsy, who are not candidates for surgical resection. A multiinstitutional, prospective, clinical study is underway to evaluate the clinical safety and efficacy of this novel treatment modality. Technical improvement of this system along with accumulation of expe- rience from its clinical use could lead to the development of a system that would accurately detect and efficiently abort any detected epileptiform activity. Acknowledgments The authors wish to thank David Greene from NeuroPace, Inc. (Mountain View, CA) for his valuable assistance. The authors also wish to acknowledge their appreciation and thanks to Aaron Barth and Stacy Perry for assistance in the preparation of this chapter. References 1. Aarabi, A., Wallois, F., and Grebe, R. (2006). Automated neonatal seizure detection: a multistage classification system through feature selection based on relevance and redundancy analysis. Clin. Neurophysiol. , 117(2):328–340. 2. Arai, A. and Lynch, G. (1998). AMPA receptor desensitization modulates synaptic responses induced by repetitive afferent stimulation in hippocampal slices. Brain Res. , 799(2):235–242. 3. Benabid, A L., Koudsie, A., Chabardes, S., et al. (2004). Subthalamic nucleus and substantia nigra pars reticulata stimulation: the Grenoble experience. In Luders, H.O., Ed., Deep Brain Stimulation and Epilepsy . Marting Dunitz, London, p. 335–348. 4. Bikson, M., Lian, J., Hahn, P.J., et al. (2001). Suppression of epileptiform activity by high frequency sinusoidal fields in rat hippocampal slices. J. Physiol. , 531(Pt 1):181–191. 5. Brown-Sequard, C.E. (1856–1857). Researches on epilepsy: its artificial production in animals, and its etiology, nature and treatment in man. Boston Med. Surg. J. : p. 55–57. 6. Chernihovskyi, A., Mormann, F., Muller, M., et al. (2005). EEG analysis with nonlinear excitable media. J. Clin. Neurophysiol. , 22(5):314–329. 7. Chkhenkeli, S.A., Sramka, M., Lortkipandze, G.S., et al. (2004). Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy. Clin. Neurol. Neurosurg. , 106(4):318–329. 8. Contzen, R. and Witte, O.W. (1994). Epileptic activity can induce both long-lasting potentiation and long-lasting depression. Brain Res. , 653(1–2):340–344. 9. Cooper, I.S., Amin, I., Riklan, M., et al. (1976). Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies. Arch. Neurol., 33(8):559–570. 10. Cooper, I.S. and Upton, A.R. (1978). Effects of cerebellar stimulation on epilepsy, the EEG and cerebral palsy in man. Electroencephalogr. Clin. Neurophysiol. Suppl., 34:349–354. 11. Cooper, I.S., Upton, A.R., and Amin, I. (1980). Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man. Appl. Neurophysiol. , 43(3–5):244–258. 12. Dudek, S.M. and Bear, M.F. (1993). Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus. J. Neurosci., 13(7):2910–2918. 13. Dudek, F.E., Yasumura, T., and Rash, J.E. (1998). “Non-synaptic” mechanisms in seizure and epileptogenesis. Cell. Biol. Int. 22:793–805. 14. Durand, D.M. and Warman, E.N. (1994). Desynchronization of epileptiform activity by extracel- lular current pulses in rat hippocampal slices. J. Physiol. , 480(Pt. 3):527–537. 8174_C004.fm Page 10 Saturday, November 3, 2007 7:40 AM Responsive Neurostimulation for Epilepsy — Neurosurgical Experience 4 -11 15. Estellar, R., Echauz, J., Tcheng, T., et al. (2001). Line length: an efficient feature of seizure onset detection. Proc. 23rd Annu. Conf. IEEE Eng. Med. Bio. Soc., pp. 1707–1709. 16. Fisher, R.S., Uematsu, S., Krauss, G.L., et al. (1992). Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. Epilepsia, 33(5):841–851. 17. Fountas, K.N., Smith, J.R., Murro, A.M., et al. (2005). Implantation of a closed-loop stimulation in the management of medically refractory focal epilepsy. A Technical Note. Stereotact. Funct. Neurosurg. , 83:153–158. 18. Fountas, K.N., Smith, J.R., Murro, A.M., et al. (2005). Closed-loop stimulation implantable system for the management of focal, medically refractory epilepsy: implantation technique and prelimi- nary results. Epilepsia , 46(S8):240–241. 19. Franaszczuk, P.J., Kudela, P., and Bergey, G.K. (2003). External excitatory stimuli can terminate bursting in neural network models. Epilepsy Res. , 53(1–2):65–80. 20. Siegel, R.E. (1976). Galen on the affected parts (de locis affectis). Book III. S. Karger, Basel, Switzerland, pp. 15–90. 21. Gowers, W.R. (1885). Epilepsy and Other Chronic Convulsive Diseases: Their Causes, Symptoms and Treatment. William Wood, New York, p. 235–236. 22. Hauser, W.A. (1995). Epidemiology of Epilepsy in Children. In Adelson, P.D. and Black, P.M., Eds., Neurosurgery Clinics of North America . W.B. Saunders Co., Philadelphia, 6(3):419–429. 23. Hauser, W.A. and Hesdorffer, D.C. (2001). Epidemiology of intractable epilepsy. In Luders, H.O. and Comair, Y.G., Eds., Epilepsy Surgery, 2nd edition . Lippincott Williams & Wilkins, Philadelphia, p. 55–61. 24. Hodaie, M., Wennberg, R.A., Dostrovsky, J.O., and Lozano, A.M. (2002). Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia , 43(6):603–608. 25. Jackson, J.H. (1868). Case of convulsive attacks arrested by stopping the aura. Lancet , 1:618–619. 26. Kang-Park, M.H., Sarda, M.A., Jones, K.H., et al. (2001). Protein phosphatases mediate depoten- tiation induced by high-intensity theraburst stimulation. J. Neurophysiol. , 89:684–690. 27. Kerrigan, J.F., Litt, B., Fisher, R.S., Craunston, S., et al. (2004). Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. Epilepsia , 45(4):346–354. 28. Kinoshita, M., Ikeda, A., Matsumoto, R., et al. (2004). Electrical stimulation on human cortex suppresses fast cortical activity and epileptic spikes. Epilepsia , 45(7):787–791. 29. Kiymik, M.K., Subasi, A., and Ozcalik, H.R. (2004). Neural networks with periodogram and autoregressive spectral analysis methods in detection of epileptic seizure. J. Med. Syst. , 28(6):511–522. 30. Labar, D. (2004). Vagal nerve stimulation: effects on seizures. In Luders, H.O., Ed., Deep Brain Stimulation and Epilepsy . Martin Dunitz, London. 31. Lesser, R.P., Kim, S.H., Beyderman, L., et al. (1999). Brief bursts of pulse stimulation terminate after-discharges caused by cortical stimulation. Neurology , 53(9):2073–2081. 32. Liang, F., Isackson, P.J., and Jones, E.G. (1996). Stimulus-dependent, reciprocal up- and down- regulation of glutamic acid decarboxylase and Ca 2+ /calmodulin-dependent protein kinase II gene expression in rat cerebral cortex. Exp. Brain Res. , 110(2):163–174. 33. Meng, L., Frei, M.G., Osorio, I., Strang, G., and Nguyen, T.Q. (2004). Gaussian mixture models of ECoG signal features for improved detection of epileptic seizures. Med. Eng. Phys. , 26(5):379–393. 34. Morrell, M. (2006). Brain stimulation for epilepsy: can scheduled or responsive neurostimulation stop seizures? Curr. Opin. Neurol. , 19(2):164–168. 35. Motamedi, G.K., Lesser, R.P., Miglioretti, D.L., et al. (2002). Optimizing parameters for terminating cortical after-discharges with pulse stimulation. Epilepsia , 43(8):836–846. 36. Munz, M., Sweasey, R., Barrett, C., et al. (2003). Preclinical testing of an implantable responsive neurostimulator system in a sheep model. In Society for Neuroscience . New Orleans, 2003. 37. Munz, M., Sweasey, R., Barret, C., et al. (2003). Implantation and testing of responsive neuro- stimulator (RNS) system for epilepsy. In American Society for Stereotactic and Functional Neuro- surgery , New York. 8174_C004.fm Page 11 Saturday, November 3, 2007 7:40 AM 4 -12 Neuroengineering 38. Murro, A.M., Park, Y.D., Bergey, G.K., et al. (2003). Multicenter study of acute responsive stimu- lation in patients with intractable epilepsy. Epilepsia, 44(Suppl. 9):326. 39. Murro, A., Park, Y., Greene, D., et al. (2002). Closed-loop neuro-stimulation in patient with intractable epilepsy. In American Clinical Neurophysiology Society, New Orleans, LA. 40. Nair, D.R., Matsumoto, R., Luders, H.O., et al. (2004). Direct cortical electrical stimulation in the treatment of epilepsy. In Luders, H.O., Ed., Deep Brain Stimulation and Epilepsy . Martin Dunitz, London. 41. Neme, S., Montgomery, E.B., Rezai, A., et al. (2004). Subthalamic nucleus stimulation in patients with intractable epilepsy: the Cleveland experience. In Luders, H.O., Ed., Deep Brain Stimulation and Epilepsy . Martin Dunitz, London, p. 349–358. 42. Netoff, T.I. and Schiff, S.J. (2002). Decreased neuronal synchronization during experimental seizures. J. Neurosci. , 22(16):7297–7307. 43. Niederhauser, J.J., Esteller, R., Echauz, J., et al. (2003). Detection of seizure precursors from depth-EEG using a sign periodogram transform. IEEE Trans. Biomed. Eng. , 50(4):449–458. 44. Oommen, J., Morrell, M., and Fisher, R.S. (2005). Experimental electrical stimulation therapy for epilepsy. Curr. Opin. Neurol. , 7(4):261–271. 45. Osorio, I., Frei, M.G., Manly, B.F., et al. (2001). An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short term clinical trials, and to multidimen- sional statistical analysis of therapeutic efficacy. J. Clin. Neurophysiol. , 18(6):533–544. 46. Osorio, I., Frei, M.G., Sunderam, S., et al. (2005). Automated seizure abatement in humans using electrical stimulation. Ann. Neurol. , 57(2):258–268. 47. Peters, T.E., Bhavaraju, N.C., Frei, M.G., and Osorio, I. (2001). Network system for automated seizure detection and contingent delivery of therapy. J. Clin. Neurophysiol. , 18(6):545–549. 48. Poliakov, A.V., Powers, R.K., Sawczuk, A., and Binder, M.D. (1996). Effects of background noise on the response of rat and cat motoneurones to excitatory current transients. J. Physiol. , 495(Pt.1):147–157. 49. Saab, M.E. and Gotman, J. (2005). A system to detect the onset of epileptic seizures in scalp EEG. Clin. Neurophysiol., 116(2):427–442. 50. Sheng, M. and Kim, M.J. (2002). Postsynaptic signaling and plasticity mechanisms. Science, 298(5594):776–780. 51. Slutzky, M.W., Cvitanovic, P., and Mogul, D.J. (2003). Manipulating epileptiform bursting in the rat hippocampus using chaos control and adaptive techniques. IEEE Trans. Biomed. Eng. , 50(5):559–570. 52. Sramka, M., Fritz, G., Gajadosova, D., and Nadvornik, P. (1980). Central stimulation treatment of epilepsy. Acta Neurochir. Suppl. (Wien.), 30:183–187. 53. Sramka, M., Fritz, G., Galanda, M., and Nadvornik, P. (1976). Some observations in treatment stimulation of epilepsy. Acta Neurochir. (Wien.), (23 Suppl.):257–262. 54. Stacey, W. and Durand, D.M. (2001). Synaptic noise improves detection of subthreshold signals in hippocampal CA1 neurons. J. Neurophysiol., 86(3):1104–1112. 55. Stevens, C.F. and Tsujimoto, T. (1995). Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool. Proc. Natl. Acad. Sci., U.S.A., 92(3):846–849. 56. Subasi, A. (2006). Application of adaptive neuro-fuzzy inference system for epileptic seizure detection using wavelet feature extraction. Comput. Biol. Med., February 8; [Epub ahead of print]. 57. Subasi, A. and Ercelebi, E. (2005). Classification of EEG signals using neural network and logistic regression. Comput. Meth. Prog. Biomed., 78(2):87–99. 58. Velasco, F., Carrillo-Ruiz, J.D., Brito, F., et al. (2005). Double-blind, randomized controlled pilot study of bi-lateral cerebellar stimulation for treatment of intractable motor seizures. Epilepsia, 46:1071–1081. 59. Velasco, F., Velasco, M., Jimenez, F., et al.(2001). Stimulation of the central median thalamic nucleus for epilepsy. Stereotact. Funct. Neurosurg., 77(1–4):228–232. 8174_C004.fm Page 12 Saturday, November 3, 2007 7:40 AM Responsive Neurostimulation for Epilepsy — Neurosurgical Experience 4-13 60. Velasco, F., Velasco, M., Ogarrio, C., and Fanghanel, G. (1987). Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia, 28(4):421–430. 61. Velasco, M., Velasco, F., and Velasco, A.L. (2001). Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures. J. Clin. Neurophysiol., 18(6):495–513. 62. Velasco, F., Velasco, M., Velasco, A.L., et al. (2001). Electrical stimulation for epilepsy: stimulation of hippocampal foci. Stereotact. Funct. Neurosurg., 77(1–4):223–227. 63. Wagenaar, D.A., Madhavan, R., Pine, J., and Potter, S.M. (2005). Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation. J. Neurosci., 25(3):680–688. 64. Zucker, R.S. and Regehr, W.G. (2002). Short-term synaptic plasticity. Annu. Rev. Physiol., 64:355–405. 8174_C004.fm Page 13 Saturday, November 3, 2007 7:40 AM 8174_C004.fm Page 14 Saturday, November 3, 2007 7:40 AM 5 -1 5 Responsive Neurostimulation for Epilepsy: RNS ™ Technology and Clinical Studies 5.1 Introduction and Background 5 -1 Clinical Market and Relevance of the Therapy · Review of Other Technologies 5.2 Fundamental Neuroscience: Mechanism of Action 5 -2 Mechanisms and Physiology of Epilepsy 5.3 Technological Innovation 5 -3 Origin of Responsive Neurostimulation Technology · Description and Implementation of Technology 5.4 Clinical Studies 5 -8 eRNS Study · Implantable RNS™ System Feasibility Study · Implantable RNS™ System Pivotal Study 5.5 Conclusions, Discussion, and Future Directions 5 -9 References 5 -10 5.1 Introduction and Background 5.1.1 Clinical Market and Relevance of the Therapy Epilepsy is a neurological disorder that affects 2.3 million people in the United States and as many as fifty million people worldwide [Begley et al., 2000]. Perhaps half have intractable epilepsy; that is, seizures cannot be controlled by antiepileptic drug (AED) therapy, and/or there are side effects from AEDs that adversely impact quality of life. The ketogenic diet, the vagus nerve stimulator, and epilepsy surgery are other treatment options. However, many persons with epilepsy are left without treatment that is effica- cious, tolerable, and acceptable. Device-based therapies may provide additional therapeutic options. One approach to treating medically intractable localization-related epilepsy with partial onset seizures is to provide focal stimulation in response to electrographic epileptiform activity. The NeuroPace ® RNS ™ system includes a cranially implanted responsive neurostimulator that continuously monitors electro- corticographic (ECoG) activity from intracranial electrodes, detects electrographic events of significance according to programmable detection algorithms, and provides responsive stimulation. The intent is to modify abnormal electrographic activity in an effort to prevent or terminate clinically evident seizures. Thomas K. Tcheng and Martha Morrell 8174_C005.fm Page 1 Monday, October 29, 2007 2:27 PM [...]... and Patient Selection Technique 6-1 6 -3 6-4 6-6 6-7 6-9 Pariventricular Gray Electrode Placement · Thalamic and Internal Capsule Placement · Chronic Stimulation Donald E Richardson 6.7 Troubleshooting 6.8 Complications and Side Effects 6.9 Results 6.10 Discussion References 6-1 3 6-1 4 6-1 4 6-1 5 6-1 6 6.1 Introduction Electrical stimulation of the... Lead 1, electrode 2 Lead 1, electrode 3 Lead 1, electrode 4 Lead 2, electrode 1 Lead 2, electrode 2 Lead 2, electrode 3 Lead 2, electrode 4 Hz Electrode Amp 2 Amp 3 Amp 4 + + + + - 100 75 50 25 Percent 5-7 50 0 –50 B 0 10 20 30 40 50 60 70 80 90 FIGURE 5 .3 (See color insert following page 1 5-4 ) Example of one channel from a stored ECoG, along with its spectrogram The x-axis is in seconds The upper panel... 174: 135 1– 135 4 1971 28 Mazars, G., Roge, R., and Mazars, Y Stimulation of the spinothalamic fasciculus and their bearing on the physiology of pain Rev Neurology: 136 – 138 , 1960 29 Melzack, R and Wall, P.D Pain mechanisms: a new theory Science 150(699):971–979, 1965 30 Meyerson, B.A Biochemistry of pain relief with intracerebral stimulation Few facts and many hypotheses Acta Neurochir 30 (suppl):229– 237 ,... for pain relief Plotkin (35 ) in South Africa obtained 60 to 65% long-term good results in 60 patients with a variety of chronic pain syndromes Ray and Burton (37 ) reported 76% good results in 28 patients and suggest intraoperative testing is a good predictor of the long-term results, which has been our observation as well Mundinger and Salomao (31 ) report 53% good results in 32 cases, with a variety... and Liebeskind, J.C Monoaminergic mechanisms of stimulation-produced analgesia Brain Res 94:279–296, 1975 3 Akil, H and Richardson, D.E Contrast medium causes the apparent increase in beta-endorphin levels in human CSF following brain stimulation [letter] Pain 23: 301 30 4, 1985 4 Akil, H., Mayer, O.J., and Liebeskind, J.C Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist Science... that activation of this system releases endogenous 8174_C006.fm Page 4 Tuesday, November 6, 2007 8:51 AM 6-4 Neuroengineering Stimulation Sites Raphe Nuclei β-Endorphine Tract β-Endorphine Cell Group Descending Serotonin Pathway FIGURE 6.2 Stimulation sites tested in the human melano-opio-cortin (beta-endorphin) pathway (Appl Neurophysiol 45:116–122, 1982.) opiates into the ventricular fluid and analgesia... Neurochir 30 (suppl):229– 237 , 1980 31 Mundinger, F and Salomao, J.F Deep brain stimulation in mesencephalic lemniscus medialis for chronic pain Acta Neurochir 30 (suppl):245–258, 1980 32 Nandi, D., Aziz, T., Carter, H., and Stein, J Thalamic field potentials in chronic central pain treated by periventricular gray stimulation — a series of eight cases Pain 101:97–107, 20 03 33 Oliveras, J.L., Hosobuchi, Y.,... Norepinephrine (NE) Parabrachial Nucleus Norepinephrine (NE) Raphe Magnus Nucleus Serotonin (5-HT) Descending Inhibitory Tract Serotonin (5-HT) and Norepinephrine (NE) FIGURE 6 .3 (See color insert following page 1 5-4 ) The beta-endorphin serotonin norepinephrin pain modulation system (Neurosurg Clin N Am 6(1): 135 –144, 1995.) inhibition by dorsal column stimulation can only be obtained by sectioning the... 8:51 AM Deep Brain Stimulation for Pain Management 6-1 7 22 Kumar, K., Wyant, G.M., and Nath, R Deep brain stimulation for control of intractable pain in humans, present and future: A ten-year follow-up Neurosurgery 26:774–781, 1990 23 Kumar, K., Toth, C., and Nath, R.K Deep brain stimulation for intractable pain: a 15-year experience Neurosurgery 40: 736 –747, 1997 24 Landau, B and Levy, R v1: Neuromodulation... medically refractory chronic pain Ann Rev Med 44:279–287, 19 93 25 Levy, R.M., Lamb, R.N., and Adams, J.E Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature Neurosurgery 21:885–8 93, 1987 26 Levy, R.M Deep brain stimulation for treatment of intractable pain Neurosurg Clin N Am 14 :38 9 39 9, 20 03 27 Mayer, O.J., Wotfle, T.L., Akil, H., Carter, B., and Liebeskind, . Neurosurg. , 106(4) :31 8 32 9. 8. Contzen, R. and Witte, O.W. (1994). Epileptic activity can induce both long-lasting potentiation and long-lasting depression. Brain Res. , 6 53( 1–2) :34 0 34 4. 9. Cooper,. T1-weighted volume acquisition using axial 1 . 3- mm slices with zero slice-gap. This is followed by a whole-head CT scan using 3- mm slices with zero slice-gap. The two data sets are imported over. terminate after-discharges caused by cortical stimulation. Neurology , 53( 9):20 73 2081. 32 . Liang, F., Isackson, P.J., and Jones, E.G. (1996). Stimulus-dependent, reciprocal up- and down- regulation