J Neurol Surg A Cent Eur Neurosurg 2021; 82(06): 568-580
DOI: 10.1055/s-0041-1725954
Review Article

Clinical Efficacy and Safety Profile of Anterior Thalamic Stimulation for Intractable Epilepsy

Michał Sobstyl
1   Department of Neurosurgery, Institute of Psychiatry and Neurology, Warszawa, Poland
1   Department of Neurosurgery, Institute of Psychiatry and Neurology, Warszawa, Poland
Szczepan Iwański
2   2nd Department of Neurology, Institute of Psychiatry and Neurology, Warszawa, Poland
Marcin Rylski
3   Department of Neuroradiology, Institute of Psychiatry and Neurology, Warszawa, Poland
4   Department of Clinical Cytology, Centrum Medyczne Ksztalcenia Podyplomowego, Warszawa, Poland
› Author Affiliations


Introduction Deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) is a neuromodulation therapy for patients with refractory partial seizures. The ANT is the structure of a limbic system with abundant neuronal connections to temporal and frontal brain regions that participate in seizure propagation circuitry.

State of the Art We have performed a literature search regarding the clinical efficacy of ANT DBS. We discuss the surgical technique of the implantation of DBS electrodes with special attention paid to the targeting methods of the ANT. Moreover, we present in detail the clinical efficacy of ANT DBS, with a special emphasis on the stimulation parameters, a stimulation mode, and polarity. We also report all adverse events and present the current limitations of ANT DBS.

Clinical Implications In general, the safety profile of DBS in intractable epilepsy patients is good, with a low rate of surgery, hardware-related, and stimulation-induced adverse events. No significant cognitive declines or worsening of depressive symptoms was noted. At long-term follow-up, the quality-of-life scores have improved. The limitations of ANT DBS studies include a limited number of patients treated and mostly open-label designs with only one double-blind, randomized multicenter trial. Most studies do not report the etiology of intractable epilepsy or they include nonhomogeneous groups of patients affected by intractable epilepsy. There are no guidelines for setting initial stimulation parameters. All the variables mentioned may have a profound impact on the final outcome.

Conclusions ANT DBS appears to be a safe and efficacious treatment, particularly in patients with refractory partial seizures (three-quarters of patients gained at least 50% seizure reduction after 5 years). ANT DBS reduces most effectively the seizures originating in the temporal and frontal lobes. The published results of ANT DBS highlight promise and hope for patients with intractable epilepsy.

Publication History

Received: 02 July 2020

Accepted: 16 December 2020

Article published online:
14 June 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342 (05) 314-319
  • 2 Brodie MJ, Dichter MA. Established antiepileptic drugs. Seizure 1997; 6 (03) 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 A global survey on epilepsy surgery, 1980-1990: a report by the Commission on Neurosurgery of Epilepsy, the International League Against Epilepsy. Epilepsia 1997; 38 (02) 249-255
  • 5 Scherrmann J, Hoppe C, Kral T, Schramm J, Elger CE. Vagus nerve stimulation: clinical experience in a large patient series. J Clin Neurophysiol 2001; 18 (05) 408-414
  • 6 Mirski MA, Rossell LA, Terry JB, Fisher RS. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res 1997; 28 (02) 89-100
  • 7 Mirski MA, Ferrendelli JA. Interruption of the connections of the mammillary bodies protects against generalized pentylenetetrazol seizures in guinea pigs. J Neurosci 1987; 7 (03) 662-670
  • 8 Upton AR, Cooper IS, Springman M, Amin I. Suppression of seizures and psychosis of limbic system origin by chronic stimulation of anterior nucleus of the thalamus. Int J Neurol 1985–1986 19–20: 223-230
  • 9 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 (04) 346-354
  • 10 Klinger NV, Mittal S. Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy. Clin Neurol Neurosurg 2016; 140: 11-25
  • 11 Child ND, Benarroch EE. Anterior nucleus of the thalamus: functional organization and clinical implications. Neurology 2013; 81 (21) 1869-1876
  • 12 Hodaie M, Wennberg RA, Dostrovsky JO, Lozano AM. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia 2002; 43 (06) 603-608
  • 13 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 (02) 342-347
  • 14 Osorio I, Overman J, Giftakis J, Wilkinson SB. High frequency thalamic stimulation for inoperable mesial temporal epilepsy. Epilepsia 2007; 48 (08) 1561-1571
  • 15 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
  • 16 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 (05) 899-908
  • 17 Lee KJ, Shon YM, Cho CB. Long-term outcome of anterior thalamic nucleus stimulation for intractable epilepsy. Stereotact Funct Neurosurg 2012; 90 (06) 379-385
  • 18 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
  • 19 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 (06) 802-811
  • 20 Kim SH, Lim SC, Kim J, Son BC, Lee KJ, Shon YM. Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: a 11-year, single center experience. Seizure 2017; 52: 154-161
  • 21 Ooi YC, Styliaras JC, Sharan A. Thalamic stimulation for epilepsy. Neurosurg Clin N Am 2011; 22 (04) 457-464 , v–vi
  • 22 Salanova V. Deep brain stimulation for epilepsy. Epilepsy Behav 2018; 88S: 21-24
  • 23 Schuepbach WM, Rau J, Knudsen K. et al; EARLYSTIM Study Group. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med 2013; 368 (07) 610-622
  • 24 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 (07) 823-829
  • 25 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 (02) 268-275
  • 26 Keller SS, O'Muircheartaigh J, Traynor C, Towgood K, Barker GJ, Richardson MP. Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity. Epilepsia 2014; 55 (02) 306-315
  • 27 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 (08) 812-817
  • 28 Sitnikov AR, Grigoryan YA, Mishnyakova LP. Bilateral stereotactic lesions and chronic stimulation of the anterior thalamic nuclei for treatment of pharmacoresistant epilepsy. Surg Neurol Int 2018; 9: 137
  • 29 Sudhyadhom A, Haq IU, Foote KD, Okun MS, Bova FJ. 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. 02) T44-T52
  • 30 Zumsteg D, Lozano AM, Wennberg RA. Mesial temporal inhibition in a patient with deep brain stimulation of the anterior thalamus for epilepsy. Epilepsia 2006; 47 (11) 1958-1962
  • 31 Khan S, Wright I, Javed S. et al. High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma. Epilepsia 2009; 50 (06) 1608-1611
  • 32 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
  • 33 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 (01) 141-150
  • 34 Lee KJ, Jang KS, Shon YM. Chronic deep brain stimulation of subthalamic and anterior thalamic nuclei for controlling refractory partial epilepsy. Acta Neurochir Suppl (Wien) 2006; 99: 87-91
  • 35 Kulju T, Haapasalo J, Lehtimäki K, Rainesalo S, Peltola J. Similarities between the responses to ANT-DBS and prior VNS in refractory epilepsy. Brain Behav 2018; 8 (06) e00983
  • 36 Park HR, Choi SJ, 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 (03) 176-182
  • 37 Jaseja H. Deep brain stimulation in intractable epilepsy: postulated optimal stimulation parameters. Epilepsy Behav 2013; 29 (03) 597-598
  • 38 Järvenpää S, Peltola J, Rainesalo S, Leinonen E, Lehtimäki K, Järventausta K. Reversible psychiatric adverse effects related to deep brain stimulation of the anterior thalamus in patients with refractory epilepsy. Epilepsy Behav 2018; 88: 373-379
  • 39 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 (09) 1525-1532 , discussion 1532
  • 40 Papez J. A proposed mechanism of emotion. Arch Neurol Psychiatry 1937; 38: 725-743
  • 41 Oh YS, Kim HJ, Lee KJ, Kim YI, Lim SC, Shon YM. Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients. Seizure 2012; 21 (03) 183-187
  • 42 Novais F, Pestana LC, Loureiro S, Andrea M, Figueira ML, Pimentel J. Predicting de novo psychopathology after epilepsy surgery: a 3-year cohort study. Epilepsy Behav 2019; 90: 204-208
  • 43 Doležalová I, Kunst J, Kojan M, Chrastina J, Baláž M, Brázdil M. Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation. Epilepsy Behav Rep 2019; 12: 100344
  • 44 Tröster AI, Meador KJ, Irwin CP, Fisher RS. SANTE Study Group. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure 2017; 45: 133-141