Vol 58, No 3 (2024)
Review Article
Published online: 2024-06-12

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Deep brain stimulation of anterior nucleus and centromedian nucleus of thalamus in treatment for drug-resistant epilepsy

Michał Sobstyl1, Magdalena Konopko2, Aleksandra Wierzbicka3, Marek Prokopienko1, Tadeusz Pietras4, Kasper Sipowicz5
Pubmed: 38864766
Neurol Neurochir Pol 2024;58(3):256-273.


Introduction. Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for resective surgery. For these patients, deep brain stimulation (DBS) may constitute the last resort in the treatment of DRE.

State of the art. We undertook a systematic review of the current literature on DBS efficacy and the safety of two thalamic nuclei–anterior nucleus of the thalamus (ANT) and the centromedian nucleus of the thalamus in the management of patients with DRE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL) was conducted.

Clinical implications. We found 30 articles related to ANT DBS and 13 articles related to CMN DBS which were further analysed. Based on the clinical research articles, we found a mean seizure frequency reduction for both thalamic nuclei. For ANT DBS, the mean seizure frequency reduction ranged from 48% to 75%, and for CMN DBS from 46.7% to 91%. The responder rate (defined as at least 50% reduction in seizure frequency) was reported to be 53.2-75% for patients after ANT DBS and 50-90% for patients after CMN DBS.

Future directions. ANT and CMN DBS appear to be safe and efficacious treatments, particularly in patients with refractory partial seizures and primary generalised seizures. ANT DBS reduces most effectively seizures originating in the temporal and frontal lobes. CMN DBS reduces mostly primary generalised tonic-clonic and atypical absences and atonic seizures. Seizures related to Lennox-Gastaut syndrome respond very favourably to CMN DBS.

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  1. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000; 342(5): 314–319.
  2. Brodie MJ, Dichter MA, Brodie MJ. Established antiepileptic drugs. Seizure. 1997; 6(3): 159–174.
  3. Téllez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain. 2005; 128(Pt 5): 1188–1198.
  4. Cramer SW, McGovern RA, Wang SG, et al. Resective epilepsy surgery: assessment of randomized controlled trials. Neurosurg Rev. 2021; 44(4): 2059–2067.
  5. Ma BB, Rao VR. Responsive neurostimulation: Candidates and considerations. Epilepsy Behav. 2018; 88: 388–395.
  6. Geller EB, Skarpaas TL, Gross RE, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy. Epilepsia. 2017; 58(6): 994–1004.
  7. Fisher R, Salanova V, Witt T, et al. SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010; 51(5): 899–908.
  8. Fisher RS. Deep brain stimulation of thalamus for epilepsy. Neurobiol Dis. 2023; 179: 106045.
  9. McInnes MDF, Moher D, Thombs BD, et al. Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement. JAMA. 2018; 319(4): 388–396.
  10. Upton AR, Cooper IS, Springman M, et al. Suppression of seizures and psychosis of limbic system origin by chronic stimulation of anterior nucleus of the thalamus. Int J Neurol. 1985; 19-20: 223–230.
  11. Kerrigan JF, Litt B, Fisher RS, et al. Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. Epilepsia. 2004; 45(4): 346–354.
  12. Child ND, Benarroch EE, et al. Anterior nucleus of the thalamus: functional organization and clinical implications. Neurology. 2013; 81(21): 1869–1876.
  13. Hodaie M, Wennberg RA, Dostrovsky JO, et al. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia. 2002; 43(6): 603–608.
  14. Klinger NV, Mittal S, et al. Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy. Clin Neurol Neurosurg. 2016; 140: 11–25.
  15. Lim SN, Lee ST, Tsai YT, et al. Electrical stimulation of the anterior nucleus of the thalamus for intractable epilepsy: a long-term follow-up study. Epilepsia. 2007; 48(2): 342–347.
  16. Osorio I, Overman J, Giftakis J, et al. High frequency thalamic stimulation for inoperable mesial temporal epilepsy. Epilepsia. 2007; 48(8): 1561–1571.
  17. Andrade DM, Zumsteg D, Hamani C, et al. Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy. Neurology. 2006; 66(10): 1571–1573.
  18. Lee KJ, Shon YM, Cho CB. Long-term outcome of anterior thalamic nucleus stimulation for intractable epilepsy. Stereotact Funct Neurosurg. 2012; 90(6): 379–385.
  19. Salanova V, Witt T, Worth R, et al. SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015; 84(10): 1017–1025.
  20. Salanova V, Sperling MR, Gross RE, et al. SANTÉ Study Group. The SANTÉ study at 10 years of follow-up: Effectiveness, safety, and sudden unexpected death in epilepsy. Epilepsia. 2021; 62(6): 1306–1317.
  21. Kim SH, Lim SC, Kim J, et al. Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: A 11-year, single center experience. Seizure. 2017; 52: 154–161.
  22. Krishna V, King NK, Sammartino F, et al. Anterior Nucleus Deep Brain Stimulation for Refractory Epilepsy: Insights Into Patterns of Seizure Control and Efficacious Target. Neurosurgery. 2016; 78(6): 802–811.
  23. Lee KJ, Jang KS, Shon YM, et al. Chronic deep brain stimulation of subthalamic and anterior thalamic nuclei for controlling refractory partial epilepsy. Acta Neurochir Suppl. 2006; 99: 87–91.
  24. Sitnikov AR, Grigoryan YuA, Mishnyakova LP. Bilateral stereotactic lesions and chronic stimulation of the anterior thalamic nuclei for treatment of pharmacoresistant epilepsy. Surg Neurol Int. 2018; 9: 137.
  25. Piacentino M, Durisotti C, Garofalo PG, et al. Anterior thalamic nucleus deep brain Stimulation (DBS) for drug-resistant complex partial seizures (CPS) with or without generalization: long-term evaluation and predictive outcome. Acta Neurochir (Wien). 2015; 157(9): 1525–32; discussion 1532.
  26. Herrman H, Egge A, Konglund AE, et al. Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study. Acta Neurol Scand. 2019; 139(3): 294–304.
  27. Park HR, Choi SuJ, Joo EY, et al. The Role of Anterior Thalamic Deep Brain Stimulation as an Alternative Therapy in Patients with Previously Failed Vagus Nerve Stimulation for Refractory Epilepsy. Stereotact Funct Neurosurg. 2019; 97(3): 176–182.
  28. Koeppen JA, Nahravani F, Kramer M, et al. Electrical Stimulation of the Anterior Thalamus for Epilepsy: Clinical Outcome and Analysis of Efficient Target. Neuromodulation. 2019; 22(4): 465–471.
  29. Herrera ML, Suller-Marti A, Parrent A, et al. Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy: A Canadian Experience. Can J Neurol Sci. 2021; 48(4): 469–478.
  30. Järvenpää S, Lehtimäki K, Rainesalo S, et al. Improving the effectiveness of ANT DBS therapy for epilepsy with optimal current targeting. Epilepsia Open. 2020; 5(3): 406–417.
  31. Tassigny D, Soler-Rico M, Delavallée M, et al. Anterior thalamic nucleus deep brain stimulation for refractory epilepsy: Preliminary results in our first 5 patients. Neurochirurgie. 2020; 66(4): 252–257.
  32. Schaper FL, Plantinga BR, Colon AJ, et al. Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control? Neurosurgery. 2020; 87(3): 602–610.
  33. Guo W, Koo BB, Kim JH, et al. Defining the optimal target for anterior thalamic deep brain stimulation in patients with drug-refractory epilepsy. J Neurosurg. 2020; 134(3): 1054–1063.
  34. Kaufmann E, Bötzel K, Vollmar C, et al. What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center. J Neurosurg. 2020 [Epub ahead of print]: 1–10.
  35. Tong X, Wang J, Qin L, et al. Analysis of power spectrum and phase lag index changes following deep brain stimulation of the anterior nucleus of the thalamus in patients with drug-resistant epilepsy: A retrospective study. Seizure. 2022; 96: 6–12.
  36. Miron G, Strauss I, Fried I, et al. Anterior thalamic deep brain stimulation in epilepsy patients refractory to vagus nerve stimulation: A single center observational study. Epilepsy Behav Rep. 2022; 29(20): 100563.
  37. Costa-Gertrudes R, Simão D, Franco A, et al. Anterior Nucleus of Thalamus Deep Brain Stimulation: A Clinical-Based Analysis of the Ideal Target in Drug-Resistant Epilepsy. Stereotact Funct Neurosurg. 2022; 100(2): 108–120.
  38. Yan H, Wang X, Zhang X, et al. Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome. Front Neurol. 2023; 12(14): 1169105.
  39. Peltola J, Colon AJ, Pimentel J, et al. Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry. Neurology. 2023; 100(18): e1852–e1865.
  40. Olaciregui Dague K, Witt JA, von Wrede R, et al. DBS of the ANT for refractory epilepsy: A single center experience of seizure reduction, side effects and neuropsychological outcomes. Front Neurol. 2023; 9(14): 1106511.
  41. Parisi V, Gregg NM, Lundstrom BN, et al. Temporo-Parietal Extraventricular Approach for Deep Brain Stimulation Targeting the Anterior Nucleus of the Thalamus: Institutional Experience. Neurosurgery. 2023; 93(6): 1393–1406.
  42. Sobstyl M, Konopko M, Sienkiewicz-Jarosz H, et al. Clinical efficacy and safety of anterior thalamic deep brain stimulation for intractable drug resistant epilepsy. Epilepsy Res. 2023; 195: 107199.
  43. Velasco M, Velasco F, Velasco AL, et al. Acute and chronic electrical stimulation of the centromedian thalamic nucleus: modulation of reticulo-cortical systems and predictor factors for generalized seizure control. Arch Med Res. 2000; 31(3): 304–315.
  44. Kulju T, Haapasalo J, Lehtimäki K, et al. Similarities between the responses to ANT-DBS and prior VNS in refractory epilepsy. Brain Behav. 2018; 8(6): e00983.
  45. Xu C, Qi L, Wang X, et al. Functional connectomic profile correlates with effective anterior thalamic stimulation for refractory epilepsy. Brain Stimul. 2023; 16(5): 1302–1309.
  46. Möttönen T, Katisko J, Haapasalo J, et al. Defining the anterior nucleus of the thalamus (ANT) as a deep brain stimulation target in refractory epilepsy: Delineation using 3 T MRI and intraoperative microelectrode recording. Neuroimage Clin. 2015; 7: 823–829.
  47. Lehtimäki K, Möttönen T, Järventausta K, et al. Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy. Brain Stimul. 2016; 9(2): 268–275.
  48. Jiltsova E, Möttönen T, Fahlström M, et al. Imaging of Anterior Nucleus of Thalamus Using 1.5T MRI for Deep Brain Stimulation Targeting in Refractory Epilepsy. Neuromodulation. 2016; 19(8): 812–817.
  49. Sudhyadhom A, Haq IU, Foote KD, et al. A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR). Neuroimage. 2009; 47 Suppl 2: T44–T52.
  50. Wang YC, Grewal SS, Middlebrooks EH, et al. Targeting analysis of a novel parietal approach for deep brain stimulation of the anterior nucleus of the thalamus for epilepsy. Epilepsy Res. 2019; 153: 1–6.
  51. Lehtimäki K, Coenen VA, Gonçalves Ferreira A, et al. MORE investigators. The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE). Neurosurgery. 2019; 84(1): 141–150.
  52. Balak N, Balkuv E, Karadag A, et al. Mammillothalamic and Mammillotegmental Tracts as New Targets for Dementia and Epilepsy Treatment. World Neurosurg. 2018; 110: 133–144.
  53. Gross RE, Fisher RS, Sperling MR, et al. Analysis of Deep Brain Stimulation Lead Targeting in the Stimulation of Anterior Nucleus of the Thalamus for Epilepsy Clinical Trial. Neurosurgery. 2021; 89(3): 406–412.
  54. Jaseja H. Deep brain stimulation in intractable epilepsy: postulated optimal stimulation parameters. Epilepsy Behav. 2013; 29(3): 597–598.
  55. Mirski MA, Rossell LA, Terry JB, et al. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res. 1997; 28(2): 89–100.
  56. Mirski MA, Ferrendelli JA, et al. Interruption of the connections of the mammillary bodies protects against generalized pentylenetetrazol seizures in guinea pigs. J Neurosci. 1987; 7(3): 662–670.
  57. Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry Clin Neurosci. 1995; 7(1): 103–112.
  58. Oh YS, Kim HJ, Lee KJ, et al. Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients. Seizure. 2012; 21(3): 183–187.
  59. Tröster AI, Meador KJ, Irwin CP, et al. SANTE Study Group. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure. 2017; 45: 133–141.
  60. Novais F, Pestana LC, Loureiro S, et al. Predicting de novo psychopathology after epilepsy surgery: A 3-year cohort study. Epilepsy Behav. 2019; 90: 204–208.
  61. Van der Werf YD, Witter MP, Groenewegen HJ, et al. The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Brain Res Rev. 2002; 39(2-3): 107–140.
  62. Sadikot AF, Rymar VV, et al. The primate centromedian-parafascicular complex: anatomical organization with a note on neuromodulation. Brain Res Bull. 2009; 78(2-3): 122–130.
  63. Zillgitt AJ, Haykal MA, Chehab A, et al. Centromedian thalamic neuromodulation for the treatment of idiopathic generalized epilepsy. Front Hum Neurosci. 2022; 16: 907716.
  64. Velasco AL, Velasco F, Jiménez F, et al. Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome. Epilepsia. 2006; 47(7): 1203–1212.
  65. Velasco F, Velasco M, Ogarrio C, et al. Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia. 1987; 28(4): 421–430.
  66. Fisher RS, Uematsu S, Krauss GL, et al. Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. Epilepsia. 1992; 33(5): 841–851.
  67. Velasco F, Velasco M, Jiménez F, et al. Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus. Neurosurgery. 2000; 47(2): 295–304; discussion 304.
  68. Valentín A, García Navarrete E, Chelvarajah R, et al. Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies. Epilepsia. 2013; 54(10): 1823–1833.
  69. Cukiert A, Cukiert CM, Burattini JA, et al. Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study. Seizure. 2020; 81: 304–309.
  70. Dalic LJ, Warren AEL, Malpas CB, et al. DBS of Thalamic Centromedian Nucleus for Lennox-Gastaut Syndrome (ESTEL Trial). Ann Neurol. 2022; 91(2): 253–267.
  71. Cukiert A, Burattini JA, Cukiert CM, et al. Centro-median stimulation yields additional seizure frequency and attention improvement in patients previously submitted to callosotomy. Seizure. 2009; 18(8): 588–592.
  72. Son BC, Shon YM, Choi JG, et al. Clinical Outcome of Patients with Deep Brain Stimulation of the Centromedian Thalamic Nucleus for Refractory Epilepsy and Location of the Active Contacts. Stereotact Funct Neurosurg. 2016; 94(3): 187–197.
  73. Kim SH, Lim SC, Yang DW, et al. Thalamo-cortical network underlying deep brain stimulation of centromedian thalamic nuclei in intractable epilepsy: a multimodal imaging analysis. Neuropsychiatr Dis Treat. 2017; 13: 2607–2619.
  74. Alcala-Zermeno JL, Gregg NM, Wirrell EC, et al. Centromedian thalamic nucleus with or without anterior thalamic nucleus deep brain stimulation for epilepsy in children and adults: A retrospective case series. Seizure. 2021; 84: 101–107.
  75. Torres Diaz CV, González-Escamilla G, Ciolac D, et al. Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy. Neurotherapeutics. 2021; 18(3): 1665–1677.
  76. Yang JC, Bullinger KL, Isbaine F, et al. Centromedian thalamic deep brain stimulation for drug-resistant epilepsy: single-center experience. J Neurosurg. 2022; 137(6): 1591–1600.
  77. Cukiert A, Cukiert CM, Argentoni-Baldochi M, et al. Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation. Seizure. 2011; 20(10): 748–753.
  78. Warren AEL, Dalic LJ, Bulluss KJ, et al. Targeting the centromedian thalamic nucleus for deep brain stimulation. J Neurol Neurosurg Psychiatry. 2020; 91(4): 339–349.
  79. Li J, Li Y, Gutierrez L, et al. Imaging the Centromedian Thalamic Nucleus Using Quantitative Susceptibility Mapping. Front Hum Neurosci. 2019; 9(13): 447.
  80. Cukiert A, Lehtimäki K, et al. Deep brain stimulation targeting in refractory epilepsy. Epilepsia. 2017; 58 Suppl 1: 80–84.
  81. Morel A. Stereotactic Atlas of the Human Thalamus and Basal Ganglia. New York: Informa Healthcare 2007.