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Mechanismen der tiefen Hirnstimulation

  • J. Volkmann
  • A. Kupsch

Zusammenfassung

Die tiefe Hirnstimulation ist eine empirisch basierte Therapie, die auf die Erfahrungen der intraoperativen Teststimulation bei stereotaktischen Hirnoperationen in den 50er und 60er Jahren des letzten Jahrhunderts zurückgeht. Aufgrund der klinischen Effekte unterschied man damals eine niederfrequente „aktivierende“ Stimulation (1-5 Hz), die etwa bei thalamischen Eingriffen den Tremor antrieb, von einer hochfrequenten „blockierenden“ Stimulation (50-200 Hz), die den Effekt einer nachfolgenden Läsion imitierte. Wir wissen heute, dass die tiefe Hirnstimulation in den derzeit verwendeten Zielgebieten Nucleus ventrointermedius thalami (VIM), Globus pallidus internus (GPi) und Nucleus subthalamicus (STN) einen reversiblen „läsionsähnlichen“ Effekt hat. Diese funktioneile Inhibition der entsprechenden Kerngebiete ist frequenzabhängig. Für die Thalamusstimulation konnten Benabid und Kollegen [4] zeigen, dass die zur effektiven Unterdrückung des Tremors erforderliche Stromstärke steil bis zu einer Frequenz von etwa 100 Hz abfällt und dann ein Plateau erreicht, in dem die Schwelle für die Tremorsuppression bis über 1000 Hz weitgehend konstant bleibt. Die meist verwendete Frequenz von 130 Hz entstand aus dem praktischen Bedürfnis, einen mit hoher Sicherheit wirksamen Parameter für die Testung der übrigen Stimulationseinstellungen konstant zu halten und gleichzeitig den Energieverbrauch der Stimulation zu minimieren. Auch für die STN-Stimulation [44] und die Pallidumstimulation [16, 68] wurde belegt, dass erst Frequenzen über 100 Hz wirksam sind. Insgesamt wurden die heutigen Standardparameter der tiefen Hirnstimulation (monopolar kathodisch, Frequenz: 130 Hz, Impulsbreite: 60-90, selten bis 210 μs, Amplitude: 1-3,5 V) mehr oder minder durch „Versuch und Irrtum“ etabliert [67]. Diese Vorgehensweise war klinisch möglich, weil bei den ersten Anwendungen des Verfahrens im Bereich der Bewegungsstörungen die Symptome (Tremor, Rigor oder Bradykinese) mit nur kurzer Verzögerung ansprachen und daher eine schnelle Rückmeldung über den Therapieeffekt lieferten. Bei neuen Indikationen wie der Dystonie, aber auch psychiatrischen Erkrankungen oder der Epilepsie, treten die Effekte jedoch teilweise so verzögert ein, dass es schwierig oder unmöglich ist, die Stimulationsparameter anhand klinischer Kriterien zu optimieren. Zukünftige Entwicklungen in der tiefen Hirnstimulation werden daher in zunehmendem Maße davon abhängen, die physiologischen Wirkmechanismen der Hochfrequenzstimulation (HFS) besser zu verstehen.

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Literatur

  1. 1.
    Abosch A, Kapur S, Lang AE et al. (2003) Stimulation of the subthalamic nucleus in Parkinson’s disease does not produce striatal dopamine release. Neurosurgery 53:1095–1105PubMedCrossRefGoogle Scholar
  2. 2.
    Anderson ME, Postupna N, Ruffo M (2003) Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J Neurophysiol 89:1150–1160PubMedCrossRefGoogle Scholar
  3. 3.
    Batir C, Krack P, Fraix V et al. (2002) Five year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. Mov Dis 17(Suppl 5):625Google Scholar
  4. 4.
    Benabid AL, Pollak P, Gao D et al. (1996) Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg 84:203–214PubMedCrossRefGoogle Scholar
  5. 5.
    Benazzouz A, Piallat B, Pollak P et al. (1995) Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimu-lation of the subthalamic nucleus in rats: electrophysiological data. Neurosci Lett 189:77–80PubMedCrossRefGoogle Scholar
  6. 6.
    Benazzouz A, Gao DM, Ni ZG et al. (2000) Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat. Neuroscience 99:289–295PubMedCrossRefGoogle Scholar
  7. 7.
    Bergman H, Deuschl G (2002) Pathophysiology of Parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov Disord 17(Suppl 3):S28–40PubMedCrossRefGoogle Scholar
  8. 8.
    Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436–1438PubMedCrossRefGoogle Scholar
  9. 9.
    Beurrier C, Bioulac B, Audin J et al. (2001) Highfrequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85:1351–1356PubMedGoogle Scholar
  10. 10.
    Boraud T, Bezard E, Bioulac B et al. (1996) High frequency stimulation of the internal globus pallidus (GPi) simultaneously improves parkinsonian symptoms and reduces firing frequency of GPi neurons in the MPTP-treated monkey. Neurosci Lett 215:17–20PubMedCrossRefGoogle Scholar
  11. 11.
    Brock LG, Coombs JS, Eccles JC (1952) The recording of potenzials from motoneurons with intracellular electrode. J Physiol 117:431–460PubMedGoogle Scholar
  12. 12.
    Bruet N, Windeis F, Bertrand A et al. (2001) High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats. J Neuropathol Exp Neurol 60:15–24PubMedGoogle Scholar
  13. 13.
    Carvalho GA, Nikkhah G (2001) Subthalamic nucleus lesions are neuroprotective against terminal 6-OHDA-induced striatal lesions and restore postural balancing reactions. Exp Neurol 171:405–417PubMedCrossRefGoogle Scholar
  14. 14.
    Ceballos-Baumann AO, Boecker H, Bartenstein P et al. (1999) A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity. Arch Neurol 56:997–1003PubMedCrossRefGoogle Scholar
  15. 15.
    Ceballos-Baumann AO, Boecker H, Fogel W et al. (2001) Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex. Neurology 56:1347–1354PubMedCrossRefGoogle Scholar
  16. 16.
    Coubes P, Roubertie A, Vayssiere N et al. (2000) Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus [letter]. Lancet 355:2220–2221PubMedCrossRefGoogle Scholar
  17. 17.
    Davis KD, Taub E, Houle S et al. (1997) Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nature Medicine 3:671–674PubMedCrossRefGoogle Scholar
  18. 18.
    DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285PubMedCrossRefGoogle Scholar
  19. 19.
    Do MT, Bean BP (2003) Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron 39:109–120PubMedCrossRefGoogle Scholar
  20. 20.
    Dostrovsky JO, Levy R, Wu JP et al. (2000) Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 84:570–574PubMedGoogle Scholar
  21. 21.
    Fukuda M, Mentis MJ, Ma Y et al. (2001) Networks mediating the clinical effects of pallidal brain stimulation for Parkinson’s disease: a PET study of resting-state glucose metabolism. Brain 124:1601–1609PubMedCrossRefGoogle Scholar
  22. 22.
    Fukuda M, Mentis M, Ghilardi MF et al. (2001) Functional correlates of pallidal stimulation for Parkinson’s disease. Ann Neurol 49:155–164PubMedCrossRefGoogle Scholar
  23. 23.
    Garcia L, Audin J, D’Alessandro G et al. (2003) Dual effect of high-frequency stimulation on subthalamic neuron activity. J Neurosci 23:8743–8751PubMedGoogle Scholar
  24. 24.
    Grafton ST, Waters C, Sutton J et al. (1995) Pallidotomy increases activity of motor association cortex in Parkinson’s disease: a positron emission tomographic study. Ann Neurol 37:776–783PubMedCrossRefGoogle Scholar
  25. 25.
    Hashimoto T, Elder CM, Okun MS et al. (2003) Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 23:1916–1923PubMedGoogle Scholar
  26. 26.
    Haslinger B, Boecker H, Buchel C et al. (2003) Differential modulation of subcortical target and cortex during deep brain stimulation. Neuroimage 18:517–524PubMedCrossRefGoogle Scholar
  27. 27.
    Hilker R, Voges J, Ghaemi M et al. (2003) Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans. Mov Disord 18:41–48PubMedCrossRefGoogle Scholar
  28. 28.
    Holsheimer J, Dijkstra EA, Demeulemeester H et al. (2000) Chronaxie calculated from current-duration and voltage-duration data. J Neurosci Methods 97:45–50PubMedCrossRefGoogle Scholar
  29. 29.
    Holsheimer J, Demeulemeester H, Nuttin B et al. (2000) Identification of the target neuronal elements in electrical deep brain stimulation. Eur J Neurosci 12:4573–4577PubMedGoogle Scholar
  30. 30.
    Joel D, Weiner I (1997) The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry. Brain Res Brain Res Rev 23:62–78PubMedCrossRefGoogle Scholar
  31. 31.
    Kiss ZH, Anderson T, Hansen T et al. (2003) Neural substrates of microstimulation-evoked tingling: a chronaxie study in human somatosensory thalamus. Eur J Neurosci 18:728–732PubMedCrossRefGoogle Scholar
  32. 32.
    Limousin P, Greene J, Pollak P et al. (1997) Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson’s disease. Ann Neurol 42:283–291PubMedCrossRefGoogle Scholar
  33. 33.
    Magarinos-Ascone C, Pazo JH, Macadar O et al. (2002) High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson’s disease. Neuroscience 115:1109–1117PubMedCrossRefGoogle Scholar
  34. 34.
    Marsden CD, Obeso JA (1994) The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson’s disease. Brain 117:877–897PubMedCrossRefGoogle Scholar
  35. 35.
    Mclntyre CC, Grill WM (1999) Excitation of central nervous system neurons by nonuniform electric fields. Biophys J 76:878–888CrossRefGoogle Scholar
  36. 36.
    Mclntyre CC, Grill WM (2002) Extracellular stimulation of central neurons: influence of stimulus waveform and frequency on neuronal output. J Neurophysiol 88:1592–1604Google Scholar
  37. 37.
    Meissner W, Reum T, Paul G et al. (2001) Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats. Neurosci Lett 303:165–168PubMedCrossRefGoogle Scholar
  38. 38.
    Meissner W, Harnack D, Paul G et al. (2002) Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats. Neurosci Lett 328:105–108PubMedCrossRefGoogle Scholar
  39. 39.
    Meissner W, Harnack D, Hoessle N et al. (2003) High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission. Neurochem Int 44:281–284CrossRefGoogle Scholar
  40. 40.
    Meissner W, Harnack D, Reese R et al. (2003) High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats. J Neurochem 85:601–609PubMedCrossRefGoogle Scholar
  41. 41.
    Middleton FA, Strick PL (2000) Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 31:236–250PubMedCrossRefGoogle Scholar
  42. 42.
    Montgomery EB Jr, Baker KB (2000) Mechanisms of deep brain stimulation and future technical developments. Neurol Res 22:259–266PubMedGoogle Scholar
  43. 43.
    Moro E, Scerrati M, Romito LM et al. (1999) Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease. Neurology 53:85–90PubMedCrossRefGoogle Scholar
  44. 44.
    Moro E, Esselink RJ, Xie J et al. (2002) The impact on Parkinson’s disease of electrical parameter settings in STN stimulation. Neurology 59:706–713PubMedCrossRefGoogle Scholar
  45. 45.
    Nowak LG, Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. I. Evidence from chronaxie measurements. Exp Brain Res 118:477–488PubMedCrossRefGoogle Scholar
  46. 46.
    Nowak LG, Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments. Exp Brain Res 118:489–500PubMedCrossRefGoogle Scholar
  47. 47.
    Paul G, Reum T, Meissner W et al. (2000) High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat. Neuroreport 11:441–444PubMedCrossRefGoogle Scholar
  48. 48.
    Paul G, Meissner W, Rein S et al. (2004) Ablation of the subthalamic nucleus protects dopaminergic phenotype but not cell survival in a rat model of Parkinson’s disease. Exp Neurol 185(2):272–280PubMedCrossRefGoogle Scholar
  49. 49.
    Perlmutter JS, Mink JW, Bastian AJ et al. (2002) Blood flow responses to deep brain stimulation of thalamus. Neurology 58:1388–1394PubMedCrossRefGoogle Scholar
  50. 50.
    Piallat B, Benazzouz A, Benabid AL (1999) Neuroprotective effect of chronic inactivation of the subthalamic nucleus in a rat model of Parkinson’s disease. J Neural Transm (Suppl 55):71–77Google Scholar
  51. 51.
    Ranck JB (1975) Which elements are excited in electrical stimulation of mammalian central nervous system? A review. Brain Research 98:417–440PubMedCrossRefGoogle Scholar
  52. 52.
    Rattay F (1999) The basic mechanism for the electrical stimulation of the nervous system. Neuroscience 89:335–346PubMedCrossRefGoogle Scholar
  53. 53.
    Rezai AR, Lozano AM, Crawley AP et al. (1999) Thalamic stimulation and functional magnetic resonance imaging: localization of cortical and subcortical activation with implanted electrodes. Technical note. J Neurosurg 90:583–590PubMedCrossRefGoogle Scholar
  54. 54.
    Salin P, Manrique C, Forni C et al. (2002) High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat. J Neurosci 22:5137–5148PubMedGoogle Scholar
  55. 55.
    Samuel M, Ceballos-Baumann AO, Turjanski N et al. (1997) Pallidotomy in Parkinson’s disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study. Brain 120:1301–1313PubMedCrossRefGoogle Scholar
  56. 56.
    Sauer H, Oertel WH (1994) Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 59:401–415PubMedCrossRefGoogle Scholar
  57. 57.
    Schroeder U, Kuehler A, Haslinger B et al. (2002) Subthalamic nucleus stimulation affects striatoanterior cingulate cortex circuit in a response conflict task: a PET study. Brain 125:1995–2004PubMedCrossRefGoogle Scholar
  58. 58.
    Schroeder U, Kuehler A, Lange KW et al. (2003) Subthalamic nucleus stimulation affects a frontotemporal network: A PET study. Ann Neurol 54:445–450PubMedCrossRefGoogle Scholar
  59. 59.
    Sestini S, Scotto di Luzio A, Ammannati F et al. (2002) Changes in regional cerebral blood flow caused by deep-brain stimulation of the subthalamic nucleus in Parkinson’s disease. J Nucl Med 43:725–732PubMedGoogle Scholar
  60. 60.
    Shen KZ, Zhu ZT, Munhall A et al. (2003) Synaptic plasticity in rat subthalamic nucleus induced by high-frequency stimulation. Synapse 50:314–319PubMedCrossRefGoogle Scholar
  61. 61.
    Strafella AP, Sadikot AF, Dagher A (2003) Subthalamic deep brain stimulation does not induce striatal dopamine release in Parkinson’s disease. Neuroreport 14:1287–1289PubMedCrossRefGoogle Scholar
  62. 62.
    Su PC, Ma Y, Fukuda M et al. (2001) Metabolic changes following subthalamotomy for advanced Parkinson’s disease. Ann Neurol 50:514–520PubMedCrossRefGoogle Scholar
  63. 63.
    Surmeier DJ, Bevan MD (2003) “The little engine that could”: voltage-dependent Na(+) channels and the subthalamic nucleus. Neuron 39:5–6PubMedCrossRefGoogle Scholar
  64. 64.
    Tai CH, Boraud T, Bezard E et al. (2003) Electro-physiological and metabolic evidence that highfrequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata. FASEB J 17:1820–1830PubMedCrossRefGoogle Scholar
  65. 65.
    Thobois S, Dominey P, Fraix V et al. (2002) Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson’s disease: a PET study. J Neurol 249:1689–1698PubMedCrossRefGoogle Scholar
  66. 66.
    Thobois S, Fraix V, Savasta M et al. (2003) Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson’s diseaseA [(11)C]-raclopride PET study. J Neurol 250:1219–1223PubMedCrossRefGoogle Scholar
  67. 61.
    Volkmann J, Herzog J, Kopper F et al. (2002) Introduction to the programming of deep brain stimulators. Mov Disord 17(Suppl 3):S181–187PubMedCrossRefGoogle Scholar
  68. 68.
    Volkmann J, Sturm V, Weiss P et al. (1998) Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson’s disease. Ann of Neurol 44:953–961CrossRefGoogle Scholar
  69. 69.
    Wang LY, Kaczmarek LK (1998) High-frequency firing helps replenish the readily releasable pool of synaptic vesicles. Nature 394:384–388PubMedCrossRefGoogle Scholar
  70. 70.
    Windeis F, Bruet N, Poupard A et al. (2000) Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Eur J Neurosci 12:4141–4146CrossRefGoogle Scholar
  71. 71.
    Windeis F, Bruet N, Poupard A et al. (2003) Influence of the frequency parameter on extracellular glutamate and gamma-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in rats. J Neurosci Res 72:259–267CrossRefGoogle Scholar
  72. 72.
    Winter C, Hosmann K, Meissner W et al. (2002) Subthalamic nucleus lesioning inhibits expression and phosphorylation of c-Jun and increases enzymatic activity in nigral neurons in the rat’s 6-OHDA model of Parkinson’s disease. Mov Dis 17(Suppl 5):S78Google Scholar
  73. 73.
    Wu YR, Levy R, Ashby P et al. (2001) Does stimulation of the GPi control dyskinesia by activating inhibitory axons? Mov Disord 16:208–216PubMedCrossRefGoogle Scholar
  74. 74.
    Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • J. Volkmann
  • A. Kupsch

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