Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Frederic L. W. V. J. Schaper; Birgit R. Plantinga; Albert J. Colon; G. Louis Wagner; Paul Boon; Nadia Blom; Erik D. Gommer; Govert Hoogland; Linda Ackermans; Rob P. W. Rouhl; Yasin Temel

doi:10.1093/neuros/nyaa141

Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Frederic L. W. V. J. Schaper^*, Birgit R. Plantinga, Albert J. Colon, G. Louis Wagner, Paul Boon, Nadia Blom, Erik D. Gommer, Govert Hoogland, Linda Ackermans, Rob P. W. Rouhl, Yasin Temel

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.

OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MIT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.

RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r' = 0.24, P = .01) and is -30% smaller (P = .015) in responders than in nonresponders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.

CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

Original language	English
Pages (from-to)	602-610
Number of pages	9
Journal	Neurosurgery
Volume	87
Issue number	3
DOIs	https://doi.org/10.1093/neuros/nyaa141
Publication status	Published - Sept 2020

Keywords

Neuromodulation
DRE
Drug-resistant epilepsy
Thalamus
Mammillothalamic tract
White matter stimulation
HIGH-FREQUENCY STIMULATION
ANTERIOR NUCLEUS
ELECTRICAL-STIMULATION
THALAMUS
TARGET
MRI
CIRCUITS

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@article{139bd9e29426497bb1ea57eecbb14bc4,

title = "Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?",

abstract = "BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MIT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r' = 0.24, P = .01) and is -30% smaller (P = .015) in responders than in nonresponders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.",

keywords = "Neuromodulation, DRE, Drug-resistant epilepsy, Thalamus, Mammillothalamic tract, White matter stimulation, HIGH-FREQUENCY STIMULATION, ANTERIOR NUCLEUS, ELECTRICAL-STIMULATION, THALAMUS, TARGET, MRI, CIRCUITS",

author = "Schaper, {Frederic L. W. V. J.} and Plantinga, {Birgit R.} and Colon, {Albert J.} and Wagner, {G. Louis} and Paul Boon and Nadia Blom and Gommer, {Erik D.} and Govert Hoogland and Linda Ackermans and Rouhl, {Rob P. W.} and Yasin Temel",

note = "Funding Information: We would like to thank Cameron C. McIntyre and Angela M. Noecker from Case Western Reserve University for their kind help in calculation of the VTAs and Frans Gielen from Medtronic for helpful discussions regarding the localization of lead contacts. The authors are greatly indebted to Geertjan van Zonneveld and Artemis Iatrou for their contribution to the figures in this article and to Bethany Isaacs and Dimo Ivanov from Maastricht University for their help in acquiring the 7T MR images. Publisher Copyright: {\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of Congress of Neurological Surgeons. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/ 4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]",

year = "2020",

month = sep,

doi = "10.1093/neuros/nyaa141",

language = "English",

volume = "87",

pages = "602--610",

journal = "Neurosurgery",

issn = "0148-396X",

publisher = "Lippincott Williams & Wilkins",

number = "3",

}

TY - JOUR

T1 - Deep Brain Stimulation in Epilepsy

T2 - A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

AU - Schaper, Frederic L. W. V. J.

AU - Plantinga, Birgit R.

AU - Colon, Albert J.

AU - Wagner, G. Louis

AU - Boon, Paul

AU - Blom, Nadia

AU - Gommer, Erik D.

AU - Hoogland, Govert

AU - Ackermans, Linda

AU - Rouhl, Rob P. W.

AU - Temel, Yasin

N1 - Funding Information: We would like to thank Cameron C. McIntyre and Angela M. Noecker from Case Western Reserve University for their kind help in calculation of the VTAs and Frans Gielen from Medtronic for helpful discussions regarding the localization of lead contacts. The authors are greatly indebted to Geertjan van Zonneveld and Artemis Iatrou for their contribution to the figures in this article and to Bethany Isaacs and Dimo Ivanov from Maastricht University for their help in acquiring the 7T MR images. Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Congress of Neurological Surgeons. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/ 4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]

PY - 2020/9

Y1 - 2020/9

N2 - BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MIT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r' = 0.24, P = .01) and is -30% smaller (P = .015) in responders than in nonresponders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

AB - BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MIT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r' = 0.24, P = .01) and is -30% smaller (P = .015) in responders than in nonresponders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

KW - Neuromodulation

KW - DRE

KW - Drug-resistant epilepsy

KW - Thalamus

KW - Mammillothalamic tract

KW - White matter stimulation

KW - HIGH-FREQUENCY STIMULATION

KW - ANTERIOR NUCLEUS

KW - ELECTRICAL-STIMULATION

KW - THALAMUS

KW - TARGET

KW - MRI

KW - CIRCUITS

U2 - 10.1093/neuros/nyaa141

DO - 10.1093/neuros/nyaa141

M3 - Article

C2 - 32421806

SN - 0148-396X

VL - 87

SP - 602

EP - 610

JO - Neurosurgery

JF - Neurosurgery

IS - 3

ER -

Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

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Keywords

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