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Epilepsy

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Fundamentals and Clinics of Deep Brain Stimulation

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Abstract

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) DBS is a novel treatment option for refractory focal epilepsy, which is approved by the US food and drug administration (FDA) and the European authorities. This therapy is based on the hypothesis that seizures are propagated via neuronal pathways, either directly or indirectly, involving the anterior nucleus of the thalamus, and eventually cause disruption in consciousness. High-frequency stimulation of this network is expected to inhibit or prevent seizure spread. This hypothesis was supported by experimental data, as well as pilot studies. The antiepileptic effect of ANT-DBS was shown by the SANTE trial, where greater seizure reduction was observed after 3 months of active stimulation compared to sham stimulation. Long-term open-label stimulation demonstrated a clear treatment benefit with 56% and 69% median seizure reduction at 2 and 5 years, respectively. The reported response rate, defined as the percentage of patients with a greater than 50% reduction of seizures, seems somewhat better after ANT-DBS than after vagus nerve stimulation (VNS), but direct comparison trials are not available. The main patient population that showed therapeutic benefit in the published trials had frontal and temporal epilepsies with focal seizures with impaired awareness as the main seizure type. A precise lead location in the ANT seems to be critical for a favorable outcome, and stimulation of deeper structures has been associated with psychiatric side effects. From a surgical perspective, the ANT is a challenging target due to its variable location with respect to common stereotactic landmarks and nearby CSF spaces. Therefore, direct targeting of the ANT using designed MRI methods is recommended.

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References

  • Aggleton JP, O’Mara SM, Vann SD, et al. Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur J Neurosci. 2010;12:2292–307.

    Article  Google Scholar 

  • Andrade DM, Zumsteg D, Hamani C, et al. Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy. Neurology. 2006;66:1571–3.

    Article  CAS  PubMed  Google Scholar 

  • Buentjen L, Kopitzki K, Schmitt FC, et al. Direct targeting of the thalamic anteroventral nucleus for deep brain stimulation by T1-weighted magnetic resonance imaging at 3 T. Stereotact Funct Neurosurg. 2014;92:25–30.

    Article  PubMed  Google Scholar 

  • Coenen VA, Panksepp J, Hurwitz TA, et al. Human medial forebrain bundle (MFB) and anterior thalamic radiation (ATR): imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression. J Neuropsychiatry Clin Neurosci. 2012;2:223–36.

    Article  Google Scholar 

  • Cukiert A, Lehtimäki K. Deep brain stimulation targeting in refractory epilepsy. Epilepsia. 2017;58:80–4.

    Article  PubMed  Google Scholar 

  • de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet. 2011;378:1388–95.

    Article  PubMed  Google Scholar 

  • Engel J Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. 2003;60:538–47.

    Article  PubMed  Google Scholar 

  • Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899–908.

    Article  PubMed  Google Scholar 

  • Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:522–30.

    Article  PubMed  Google Scholar 

  • Gooneratne IK, Green AL, Dugan P, et al. Comparing neurostimulation technologies in refractory focal-onset epilepsy. J Neurol Neurosurg Psychiatry. 2016;87:1174–82.

    Article  PubMed  Google Scholar 

  • Heck CN, King-Stephens D, Massey AD, et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. 2014;55:432–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Heilbronner SR, Haber SN. Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders. J Neurosci. 2014;34:10041–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodaie M, Wennberg RA, Dostrovsky JO, Lozano AM. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia. 2002;43:603–8.

    Article  PubMed  Google Scholar 

  • Jankowski MM, Ronnqvist KC, Tsanov M, et al. The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation. Front Syst Neurosci. 2013;7:45.

    Article  PubMed  PubMed Central  Google Scholar 

  • Järvenpää S, Rosti-Otajärvi E, Rainesalo S, et al. Executive functions may predict outcome in deep brain stimulation of anterior nucleus of thalamus for treatment of refractory epilepsy. Front Neurol. 2018;9:324.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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;19:812–7.

    Article  PubMed  Google Scholar 

  • Jones EG. Anterior nuclei and lateral dorsal nucleus. In: The thalamus. 2nd ed. Cambridge: Cambridge University Press; 2007.

    Google Scholar 

  • 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;45:346–54.

    Article  PubMed  Google Scholar 

  • 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;78:802–11.

    Article  PubMed  Google Scholar 

  • 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:e00983.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.

    Google Scholar 

  • Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51:1069–77.

    Article  CAS  PubMed  Google Scholar 

  • Lee KJ, Jang KS, Shon YM. Chronic deep brain stimulation of subthalamic and anterior thalamic nuclei for controlling refractory partial epilepsy. Acta Neurochir Suppl. 2006;99:87–91.

    Article  CAS  PubMed  Google Scholar 

  • Lee KJ, Shon YM, Cho CB. Long-term outcome of anterior thalamic nucleus stimulation for intractable epilepsy. Stereotact Funct Neurosurg. 2012;90:379–85.

    Article  PubMed  Google Scholar 

  • 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;9:268–75.

    Article  PubMed  Google Scholar 

  • Lehtimäki K, Coenen VA, Gonçalves Ferreira A, et al. The surgical approach to the anterior nucleus of thalamus in patients with refractory epilepsy: experience from the International Multicenter Registry (MORE). Neurosurgery. 2019;84:141–50.

    Article  PubMed  Google Scholar 

  • 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;48:342–7.

    Article  PubMed  Google Scholar 

  • Mai J, Majtanik M, Paxinos G. Atlas of the human brain. 4th ed. New York: Academic; 2015.

    Google Scholar 

  • Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol. 2006;13:277–82.

    Article  CAS  PubMed  Google Scholar 

  • Morris GL 3rd, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology. 1999;53:1731–5.

    Article  PubMed  Google Scholar 

  • 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;7:823–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Möttönen T, Katisko J, Haapasalo J, et al. The correlation between intraoperative microelectrode recording and 3-Tesla MRI in patients undergoing ANT-DBS for refractory epilepsy. Stereotact Funct Neurosurg. 2016;94:86–92.

    Article  PubMed  Google Scholar 

  • Murray CJL, Lopez AD. Global comparative assessment in the health sector; disease burden, expenditures, and intervention packages. Geneva: World Health Organization; 1994.

    Google Scholar 

  • Nora T, Heinonen H, Tenhunen M, et al. Stimulation induced electrographic seizures in deep brain stimulation of the anterior nucleus of the thalamus do not preclude a subsequent favorable treatment response. Front Neurol. 2018;9:66.

    Article  PubMed  PubMed Central  Google Scholar 

  • Osorio I, Overman J, Giftakis J, Wilkinson SB. High frequency thalamic stimulation for inoperable mesial temporal epilepsy. Epilepsia. 2007;48:1561–71.

    Article  PubMed  Google Scholar 

  • Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry Clin Neurosci. 1995;7:103–12.

    Article  CAS  PubMed  Google Scholar 

  • Salanova V, Witt T, Worth R, et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015;84:1017–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaltenbrand G, Wahren W. Atlas for sterotaxy of the human brain. 2nd ed. Stuttgart: Thieme; 1998.

    Google Scholar 

  • Schaper FLWVJ, Zhao Y, Janssen MLF, et al. Single-cell recordings to target the anterior nucleus of the thalamus in deep brain stimulation for patients with refractory epilepsy. Int J Neural Syst. 2018;29:1850012.

    Article  PubMed  Google Scholar 

  • Shibata H, Naito J. Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat. Brain Res. 2005;1059:93–103.

    Article  CAS  PubMed  Google Scholar 

  • Stypulkowski PH, Giftakis JE, Billstrom TM. Development of a large animal model for investigation of deep brain stimulation for epilepsy. Stereotact Funct Neurosurg. 2011;89:111–22.

    Article  PubMed  Google Scholar 

  • Stypulkowski PH, Stanslaski SR, Denison TJ, Giftakis JE. Chronic evaluation of a clinical system for deep brain stimulation and recording of neural network activity. Stereotact Funct Neurosurg. 2013;91:220–32.

    Article  PubMed  Google Scholar 

  • van Buren JM, Borke RC. The nuclei and cerebral connections of the human thalamus. In: Variations and connections of the human thalamus. Berlin: Springer; 1972.

    Chapter  Google Scholar 

  • Van Gompel JJ, Klassen BT, Worrell GA, et al. Anterior nuclear deep brain stimulation guided by concordant hippocampal recording. Neurosurg Focus. 2015;38:E9.

    Article  PubMed  Google Scholar 

  • van Groen T, Kadish I, Wyss JM. Efferent connections of the anteromedial nucleus of the thalamus of the rat. Brain Res Brain Res Rev. 1999;30:1–26.

    Article  PubMed  Google Scholar 

  • Voges B, Schmitt F, Hamel W, et al. Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients. Epilepsia. 2015;56:99–103.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosciences and Rehabilitation, Tampere University Hospital, Tampere, Finland

    Kai Lehtimäki

  2. Department of Neurosciences and Rehabilitation/Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere University, Tampere, Finland

    Jukka Peltola

Authors
  1. Kai Lehtimäki
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  2. Jukka Peltola
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Correspondence to Kai Lehtimäki .

Editor information

Editors and Affiliations

  1. Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, The Netherlands

    Yasin Temel

  2. Department of Psychiatry, Maastricht University Medical Centre, Maastricht, The Netherlands

    Albert F.G. Leentjens

  3. Department of Neurology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Noord-Holland, The Netherlands

    Rob M.A. de Bie

  4. Department of Neurosurgery, Grenoble University Hospital Center, Grenoble, France

    Stephan Chabardes

  5. Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, ON, Canada

    Alfonso Fasano

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Lehtimäki, K., Peltola, J. (2020). Epilepsy. In: Temel, Y., Leentjens, A., de Bie, R., Chabardes, S., Fasano, A. (eds) Fundamentals and Clinics of Deep Brain Stimulation. Springer, Cham. https://doi.org/10.1007/978-3-030-36346-8_15

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  • DOI: https://doi.org/10.1007/978-3-030-36346-8_15

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-36345-1

  • Online ISBN: 978-3-030-36346-8

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