Introduction: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) and responsive neurostimulation (RNS) of the hippocampus are the predominant approaches to brain stimulation for treating mesial temporal lobe epilepsy (MTLE). Both are similarly effective at reducing seizures in drug-resistant patients, but the underlying mechanisms are poorly understood. In rare cases where it is clinically indicated to use RNS and DBS simultaneously, ambulatory electrophysiology from RNS may provide the opportunity to measure the effects of ANT DBS in the putative seizure onset zone and identify biomarkers associated with clinical improvement. Here, one such patient became seizure free, allowing us to identify and compare the changes in hippocampal electrophysiology associated with ANT stimulation and seizure freedom. Methods: Ambulatory electrocorticography and clinical history were retrospectively analyzed for a patient treated with RNS and DBS for MTLE. DBS artifacts were used to identify ANT stimulation periods on RNS recordings and measure peri-stimulus electrographic changes. Clinical history was used to determine the chronic electrographic changes associated with seizure freedom. Results: ANT stimulation acutely suppressed hippocampal gamma (25–90Hz) power, with minimal theta (4–8Hz) suppression and without clear effects on seizure frequency. Eventually, the patient became seizure free alongside the emergence of chronic gamma increase and theta suppression, which started at the same time as clobazam was introduced. Both seizure freedom and the associated electrophysiology persisted after inadvertent DBS discontinuation, further implicating the clobazam relationship. Unexpectedly, RNS detections and long episodes increased, although they were not considered to be electrographic seizures, and the patient remained clinically seizure free. Conclusion: ANT stimulation and seizure freedom were associated with distinct, dissimilar spectral changes in RNS-derived electrophysiology. The time course of these changes supported a new medication as the most likely cause of clinical improvement. Broadly, this work showcases the use of RNS recordings to interpret the effects of multimodal therapy. Specifically, it lends additional credence to hippocampal theta suppression as a biomarker previously associated with seizure reduction in RNS patients.

1.
Nair
DR
,
Laxer
KD
,
Weber
PB
,
Murro
AM
,
Park
YD
,
Barkley
GL
.
Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy
.
Neurology
.
2020 Sep
95
9
e1244
56
.
2.
Salanova
V
,
Witt
T
,
Worth
R
,
Henry
TR
,
Gross
RE
,
Nazzaro
JM
.
Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy
.
Neurology
.
2015 Mar
84
10
1017
25
.
3.
Elliott
RE
,
Morsi
A
,
Kalhorn
SP
,
Marcus
J
,
Sellin
J
,
Kang
M
.
Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response
.
Epilepsy Behav
.
2011 Jan
20
1
57
63
.
4.
Heck
CN
,
King-Stephens
D
,
Massey
AD
,
Nair
DR
,
Jobst
BC
,
Barkley
GL
.
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
(
3
):
432
41
.
5.
Fisher
R
,
Salanova
V
,
Witt
T
,
Worth
R
,
Henry
T
,
Gross
R
.
Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy
.
Epilepsia
.
2010 May
51
5
899
908
.
6.
Laxpati
NG
,
Kasoff
WS
,
Gross
RE
.
Deep brain stimulation for the treatment of epilepsy: circuits, targets, and trials
.
Neurotherapeutics
.
2014 Jul
11
3
508
26
.
7.
Geller
EB
,
Skarpaas
TL
,
Gross
RE
,
Goodman
RR
,
Barkley
GL
,
Bazil
CW
.
Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy
.
Epilepsia
.
2017 Jun
58
6
994
1004
.
8.
Salanova
V
,
Sperling
MR
,
Gross
RE
,
Irwin
CP
,
Vollhaber
JA
,
Giftakis
JE
.
The SANTÉ study at 10 years of follow-up: effectiveness, safety, and sudden unexpected death in epilepsy
.
Epilepsia
.
2021
;
62
(
6
):
1306
17
.
9.
Yang
JC
,
Bullinger
KL
,
Dickey
AS
,
Karakis
I
,
Alwaki
A
,
Cabaniss
BT
.
Anterior nucleus of the thalamus deep brain stimulation vs temporal lobe responsive neurostimulation for temporal lobe epilepsy
.
Epilepsia
.
2022
;
63
(
9
):
2290
300
.
10.
Benbadis
SR
,
Geller
E
,
Ryvlin
P
,
Schachter
S
,
Wheless
J
,
Doyle
W
.
Putting it all together: options for intractable epilepsy: an updated algorithm on the use of epilepsy surgery and neurostimulation
.
Epilepsy Behav
.
2018 Nov
88S
33
8
.
11.
Quraishi
IH
,
Mercier
MR
,
Skarpaas
TL
,
Hirsch
LJ
.
Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs
.
Epilepsia
.
2020 Jan
61
1
138
48
.
12.
Hirsch
LJ
,
Mirro
EA
,
Salanova
V
,
Witt
TC
,
Drees
CN
,
Brown
MG
.
Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system
.
Epilepsia
.
2020 Mar
61
3
408
20
.
13.
Silva
AB
,
Khambhati
AN
,
Speidel
BA
,
Chang
EF
,
Rao
VR
.
Effects of anterior thalamic nuclei stimulation on hippocampal activity: chronic recording in a patient with drug-resistant focal epilepsy
.
Epilepsy Behav Rep
.
2021 Jun
16
100467
.
14.
Lagarde
S
,
Buzori
S
,
Trebuchon
A
,
Carron
R
,
Scavarda
D
,
Milh
M
.
The repertoire of seizure onset patterns in human focal epilepsies: determinants and prognostic values
.
Epilepsia
.
2019
;
60
(
1
):
85
95
.
15.
Sisterson
ND
,
Wozny
TA
,
Kokkinos
V
,
Bagic
A
,
Urban
AP
,
Richardson
RM
.
A rational approach to understanding and evaluating responsive neurostimulation
.
Neuroinformatics
.
2020 Jun
18
3
365
75
.
16.
Seabold
S
,
Perktold
J
.
Statsmodels: econometric and statistical modeling with Python
.
Proc 9th Python Sci Conf
.
2010
92–6
.
17.
Spencer
DC
,
Sun
FT
,
Brown
SN
,
Jobst
BC
,
Fountain
NB
,
Wong
VSS
.
Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring
.
Epilepsia
.
2016 Sep
57
9
1495
502
.
18.
Arcot Desai
S
,
Tcheng
TK
,
Morrell
MJ
.
Quantitative electrocorticographic biomarkers of clinical outcomes in mesial temporal lobe epileptic patients treated with the RNS® system
.
Clin Neurophysiol
.
2019 Aug
130
8
1364
74
.
19.
Chaitanya
G
,
Toth
E
,
Pizarro
D
,
Irannejad
A
,
Riley
K
,
Pati
S
.
Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus
.
Clin Neurophysiol
.
2020 Sep
131
9
2158
67
.
20.
Scherer
M
,
Milosevic
L
,
Guggenberger
R
,
Maus
V
,
Naros
G
,
Grimm
F
.
Desynchronization of temporal lobe theta-band activity during effective anterior thalamus deep brain stimulation in epilepsy
.
Neuroimage
.
2020 Sep
218
116967
.
21.
Hodaie
M
,
Wennberg
RA
,
Dostrovsky
JO
,
Lozano
AM
.
Chronic anterior thalamus stimulation for intractable epilepsy
.
Epilepsia
.
2002
;
43
(
6
):
603
8
.
22.
Herrman
H
,
Egge
A
,
Konglund
AE
,
Ramm-Pettersen
J
,
Dietrichs
E
,
Taubøll
E
.
Anterior thalamic deep brain stimulation in refractory epilepsy: a randomized, double-blinded study
.
Acta Neurol Scand
.
2019
;
139
(
3
):
294
304
.
23.
Wang
YC
,
Kremen
V
,
Brinkmann
BH
,
Middlebrooks
EH
,
Lundstrom
BN
,
Grewal
SS
.
Probing circuit of Papez with stimulation of anterior nucleus of the thalamus and hippocampal evoked potentials
.
Epilepsy Res
.
2020 Jan
159
106248
.
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