Advertisement

Some Recent Trends and Further Promising Directions in Functional Neurosurgery

  • Travis S. Tierney
  • Tejas Sankar
  • Andres M. LozanoEmail author
Conference paper
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 117)

Abstract

The field of functional neurosurgery has developed a number of recent innovative neuromodulatory approaches to treat disease that remains resistant to the best medical therapy. These include novel surgical techniques to intervene in motor and cognitive sequelae of refractory epilepsy, neurodegenerative disease, and certain psychiatric conditions. To a large extent, much of the innovation in our field continues to be driven by a systems-level understanding of the impact of disease on the brain. For example, several groups have exploited findings from neuroimaging work to identify a number of new potential neuromodulatory targets for the treatment of refractory depression. Ongoing discoveries at the cellular and molecular level promise targeted gene or drug delivery aimed at curing disease. Neurosurgeons will certainly remain at the forefront of translating these strategies into practical clinical applications. Several randomized trials are now underway to assess the safety and efficacy of a number of new approaches, and we will continue to acquire better knowledge of optimal patient selection, identification of the most effective neuromodulatory targets, and recognition of adverse effects as these studies progress.

Keywords

Alzheimer’s disease Epilepsy Deep brain stimulation Huntington’s disease Depression Gene therapy Parkinson’s disease Pedunculopontine nucleus 

Notes

Conflict of Interest

TST and TS declare that they have no conflict of interest. AML holds intellectual property rights in the field of deep brain stimulation, and has served as a consultant for Medtronic and St. Jude corporations.

References

  1. 1.
    Benabid AL, Chabardes S, Seigneuret E (2005) Deep-brain stimulation in Parkinson’s disease: long-term efficacy and safety – what happened this year? Curr Opin Neurol 18:623–630PubMedCrossRefGoogle Scholar
  2. 2.
    Biolsi B, Cif L, Fertit HE, Robles SG, Coubes P (2008) Long-term follow-up of Huntington disease treated by bilateral deep brain stimulation of the internal globus pallidus. J Neurosurg 109:130–132PubMedCrossRefGoogle Scholar
  3. 3.
    Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268PubMedCrossRefGoogle Scholar
  4. 4.
    Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191PubMedCrossRefGoogle Scholar
  5. 5.
    Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, VanBrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ (2009) Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 73:1662–1669PubMedCrossRefGoogle Scholar
  6. 6.
    Clausen J (2009) Man, machine and in between. Nature 457:1080–1081PubMedCrossRefGoogle Scholar
  7. 7.
    Clausen J (2010) Ethical brain stimulation – neuroethics of deep brain stimulation in research and clinical practice. Eur J Neurosci 32:1152–1162PubMedCrossRefGoogle Scholar
  8. 8.
    Depression Guideline Panel (1993) Depression in primary care, vol 2, Treatment of major depression. US Department of Health and Human Services, Agency for Health Care Policy and Research; AHCPR Publication, RockvilleGoogle Scholar
  9. 9.
    Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896–908PubMedCrossRefGoogle Scholar
  10. 10.
    Dougherty DD, Weiss AP, Cosgrove GR, Alpert NM, Cassem EH, Nierenberg AA, Price BH, Mayberg HS, Fischman AJ, Rauch SL (2003) Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. J Neurosurg 99:1010–1017PubMedCrossRefGoogle Scholar
  11. 11.
    During MJ, Kaplitt MG, Stern MB, Eidelberg D (2001) Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Hum Gene Ther 12:1589–1591PubMedGoogle Scholar
  12. 12.
    Eberling JL, Jagust WJ, Christine CW, Starr P, Larson P, Bankiewicz KS, Aminoff MJ (2008) Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology 70:1980–1983PubMedCrossRefGoogle Scholar
  13. 13.
    Fasano A, Mazzone P, Piano C, Quaranta D, Soleti F, Bentivoglio AR (2008) GPi-DBS in Huntington’s disease: results on motor function and cognition in a 72-year-old case. Mov Disord 23:1289–1292PubMedCrossRefGoogle Scholar
  14. 14.
    Fava M (2003) Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 53:649–659PubMedCrossRefGoogle Scholar
  15. 15.
    Feigin A, Kaplitt MG, Tang C, Lin T, Mattis P, Dhawan V, During MJ, Eidelberg D (2007) Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson’s disease. Proc Natl Acad Sci USA 104:19559–19564PubMedCrossRefGoogle Scholar
  16. 16.
    Ferraye MU, Debu B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E, Piallat B, Krack P, Le Bas JF, Benabid AL, Chabardes S, Pollak P (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214PubMedCrossRefGoogle Scholar
  17. 17.
    Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N (2010) Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 51:899–908PubMedCrossRefGoogle Scholar
  18. 18.
    Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA (2009) Spinal cord stimulation restores locomotion in animal models of Parkinson’s disease. Science 323:1578–1582PubMedCrossRefGoogle Scholar
  19. 19.
    Fujimoto Y, Isozaki E, Yokochi F, Yamakawa K, Takahashi H, Hirai S (1997) A case of chorea-acanthocytosis successfully treated with posteroventral pallidotomy. Rinsho Shinkeigaku 37:891–894PubMedGoogle Scholar
  20. 20.
    Gasmi M, Herzog CD, Brandon EP, Cunningham JJ, Ramirez GA, Ketchum ET, Bartus RT (2007) Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson’s disease. Mol Ther 15:62–68PubMedCrossRefGoogle Scholar
  21. 21.
    Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41PubMedCrossRefGoogle Scholar
  22. 22.
    Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324:354–359PubMedCrossRefGoogle Scholar
  23. 23.
    Hamani C, McAndrews MP, Cohn M, Oh M, Zumsteg D, Shapiro CM, Wennberg RA, Lozano AM (2008) Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann Neurol 63:119–123PubMedCrossRefGoogle Scholar
  24. 24.
    Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2:e299PubMedCrossRefGoogle Scholar
  25. 25.
    Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, Henry TR, Collins SD, Vaughn BV, Gilmartin RC, Labar DR, Morris GL 3rd, Salinsky MC, Osorio I, Ristanovic RK, Labiner DM, Jones JC, Murphy JV, Ney GC, Wheless JW (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55PubMedCrossRefGoogle Scholar
  26. 26.
    Hebb MO, Garcia R, Gaudet P, Mendez IM (2006) Bilateral stimulation of the globus pallidus internus to treat choreathetosis in Huntington’s disease: technical case report. Neurosurgery 58:E383; discussion E383PubMedCrossRefGoogle Scholar
  27. 27.
    Holtzheimer PE, Kelley ME, Gross RE, Filkowski MM, Garlow SJ, Barrocas A, Wint D, Craighead MC, Kozarsky J, Chismar R, Moreines JL, Mewes K, Posse PR, Gutman DA, Mayberg HS (2012) Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry 69:150–158PubMedCrossRefGoogle Scholar
  28. 28.
    Kang GA, Heath S, Rothlind J, Starr PA (2011) Long-term follow-up of pallidal deep brain stimulation in two cases of Huntington’s disease. J Neurol Neurosurg Psychiatry 82:272–277PubMedCrossRefGoogle Scholar
  29. 29.
    Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ (2007) Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 369:2097–2105PubMedCrossRefGoogle Scholar
  30. 30.
    Kennedy SH, Giacobbe P, Rizvi SJ, Placenza FM, Nishikawa Y, Mayberg HS, Lozano AM (2011) Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry 168(5):502–510PubMedCrossRefGoogle Scholar
  31. 31.
    Kerr GK, Worringham CJ, Cole MH, Lacherez PF, Wood JM, Silburn PA (2010) Predictors of future falls in Parkinson disease. Neurology 75:116–124PubMedCrossRefGoogle Scholar
  32. 32.
    Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS, Lozano AM (2010) A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Ann Neurol 68:521–534PubMedCrossRefGoogle Scholar
  33. 33.
    LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 10:309–319PubMedCrossRefGoogle Scholar
  34. 34.
    Lipsman N, Bernstein M, Lozano AM (2010) Criteria for the ethical conduct of psychiatric neurosurgery clinical trials. Neurosurg Focus 29:E9PubMedCrossRefGoogle Scholar
  35. 35.
    Lipsman N, Giacobbe P, Bernstein M, Lozano AM (2012) Informed consent for clinical trials of deep brain stimulation in psychiatric disease: challenges and implications for trial design. J Med Ethics 38:107–111PubMedCrossRefGoogle Scholar
  36. 36.
    Lozano AM, Giacobbe P, Hamani C, Rizvi SJ, Kennedy SH, Kolivakis TT, Debonnel G, Sadikot AF, Lam RW, Howard AK, Ilcewicz-Klimek M, Honey CR, Mayberg HS (2012) A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg 116:315–322PubMedCrossRefGoogle Scholar
  37. 37.
    Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH (2008) Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461–467PubMedCrossRefGoogle Scholar
  38. 38.
    Marks WJ Jr, Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA, Taylor R, Cahn-Weiner DA, Stoessl AJ, Olanow CW, Bartus RT (2008) Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol 7:400–408PubMedCrossRefGoogle Scholar
  39. 39.
    Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA (2000) Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48:830–843PubMedCrossRefGoogle Scholar
  40. 40.
    Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT (1999) Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 156:675–682PubMedGoogle Scholar
  41. 41.
    Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660PubMedCrossRefGoogle Scholar
  42. 42.
    Mazzone P, Sposato S, Insola A, Dilazzaro V, Scarnati E (2008) Stereotactic surgery of nucleus tegmenti pedunculopontine [corrected]. Br J Neurosurg 22(Suppl 1):S33–S40PubMedCrossRefGoogle Scholar
  43. 43.
    Moro E, Hamani C, Poon YY, Al-Khairallah T, Dostrovsky JO, Hutchison WD, Lozano AM (2010) Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain 133:215–224PubMedCrossRefGoogle Scholar
  44. 44.
    Moro E, Lang AE, Strafella AP, Poon YY, Arango PM, Dagher A, Hutchison WD, Lozano AM (2004) Bilateral globus pallidus stimulation for Huntington’s disease. Ann Neurol 56:290–294PubMedCrossRefGoogle Scholar
  45. 45.
    Morrell MJ (2011) Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77:1295–1304PubMedCrossRefGoogle Scholar
  46. 46.
    Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM, Bamberg E, Hegemann P (2002) Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–2398PubMedCrossRefGoogle Scholar
  47. 47.
    Nobler MS, Oquendo MA, Kegeles LS, Malone KM, Campbell CC, Sackeim HA, Mann JJ (2001) Decreased regional brain metabolism after ect. Am J Psychiatry 158:305–308PubMedCrossRefGoogle Scholar
  48. 48.
    Pahapill PA, Lozano AM (2000) The pedunculopontine nucleus and Parkinson’s disease. Brain 123(Pt 9):1767–1783PubMedCrossRefGoogle Scholar
  49. 49.
    Pereira EA, Muthusamy KA, De Pennington N, Joint CA, Aziz TZ (2008) Deep brain stimulation of the pedunculopontine nucleus in Parkinson’s disease. Preliminary experience at Oxford. Br J Neurosurg 22(Suppl 1):S41–S44PubMedCrossRefGoogle Scholar
  50. 50.
    Rabins P, Appleby BS, Brandt J, DeLong MR, Dunn LB, Gabriels L, Greenberg BD, Haber SN, Holtzheimer PE 3rd, Mari Z, Mayberg HS, McCann E, Mink SP, Rasmussen S, Schlaepfer TE, Vawter DE, Vitek JL, Walkup J, Mathews DJ (2009) Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought. Arch Gen Psychiatry 66:931–937PubMedCrossRefGoogle Scholar
  51. 51.
    Sankar T, Tierney TS, Hamani C (2012) Noval applications of deep brain stimulation. Surg Neurol Int 3:S26–S33PubMedCrossRefGoogle Scholar
  52. 52.
    Seminowicz DA, Mayberg HS, McIntosh AR, Goldapple K, Kennedy S, Segal Z, Rafi-Tari S (2004) Limbic-frontal circuitry in major depression: a path modeling metanalysis. Neuroimage 22:409–418PubMedCrossRefGoogle Scholar
  53. 53.
    Smith JR, Fountas KN, Murro AM, Park YD, Jenkins PD, Morrell M, Esteller R, Greene D (2010) Closed-loop stimulation in the control of focal epilepsy of insular origin. Stereotact Funct Neurosurg 88:281–287PubMedCrossRefGoogle Scholar
  54. 54.
    Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L, Scarnati E, Mazzone P (2007) Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 130:1596–1607PubMedCrossRefGoogle Scholar
  55. 55.
    Sun FT, Morrell MJ, Wharen RE Jr (2008) Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics 5:68–74PubMedCrossRefGoogle Scholar
  56. 56.
    Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, Brown P (2010) Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology 74:1325–1327PubMedCrossRefGoogle Scholar
  57. 57.
    Tierney TS, Lozano AM (2013) Intervention options: functional neurosurgery. In: Morris ME, Iansek R (eds) Rehabilitation in movement disorders. Cambridge University Press, CambridgeGoogle Scholar
  58. 58.
    Tierney TS, Sankar T, Lozano AM (2011) Deep brain stimulation emerging indications. Prog Brain Res 194:83–95PubMedCrossRefGoogle Scholar
  59. 59.
    Vitek JL, Jones R, Bakay R, Hersch S (2000) Pallidotomy for Huntington’s disease. Ann Neurol 48:429Google Scholar
  60. 60.
    VNS Study Group (1995) A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. The Vagus Nerve Stimulation Study Group. Neurology 45:224–230CrossRefGoogle Scholar
  61. 61.
    Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301:63–73PubMedCrossRefGoogle Scholar
  62. 62.
    Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, Scott R, Ives N, Rick C, Daniels J, Patel S, Wheatley K (2010) Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol 9:581–591PubMedCrossRefGoogle Scholar
  63. 63.
    World Health Organization (2001) Chapter 2: Burden of mental and behavioral disorders. In: The WHO report 2001: mental health, new understanding. New Hope. http://www.who.int/whr/2001/chapter2/en/Index3.html. Last Accessed on 28 Feb 2011
  64. 64.
    Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K (2010) Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc 5:439–456PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Travis S. Tierney
    • 1
  • Tejas Sankar
    • 2
  • Andres M. Lozano
    • 2
    • 3
    Email author
  1. 1.Department of NeurosurgeryBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Division of NeurosurgeryToronto Western HospitalTorontoCanada
  3. 3.Department of NeurosurgeryUniversity of Toronto, Toronto Western HospitalTorontoCanada

Personalised recommendations