Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Elder, Christopher; Friedman, Daniel; Devinsky, Orrin; Doyle, Werner; Dugan, Patricia

doi:10.1002/epi4.12300

Cited by 72 publications

(56 citation statements)

References 24 publications

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“…Unlike the anterior thalamus that is implicated in propagation of temporal lobe seizures, the midline thalamus can be within the seizure onset network in TLE that needs to be clarified in a larger cohort. With the widespread acceptance of robot‐assisted sEEG investigation to localize epilepsies, electrophysiological sampling from the thalamus is feasible and maybe justifiable in selected patients where the demonstration of early thalamic recruitment can be used to develop adjunctive neurostimulation therapies (‐like implanting responsive neurostimulation in the thalamus) that complement resection.…”

Section: Resultsmentioning

confidence: 99%

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy

Romeo

Roach

Tóth

et al. 2019

Ann Clin Transl Neurol

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The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0–13 sec) and propagation (9–60 sec). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure‐induced in the hippocampus rapidly recruited the thalamus. Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.

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Section: Resultsmentioning

confidence: 99%

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy

Romeo

Roach

Tóth

et al. 2019

Ann Clin Transl Neurol

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“…; Elder et al . ) and recent optogenetic work has renewed interest in the cerebellum as a potential therapeutic target (Krook‐Magnuson et al . ; Kros et al .…”

Section: Introductionmentioning

confidence: 99%

Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

Streng

Krook-Magnuson

2019

The Journal of Physiology

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Key pointsr On-demand optogenetic inhibition of glutamatergic neurons in the fastigial nucleus of the cerebellum does not alter hippocampal seizures in a mouse model of temporal lobe epilepsy.r In contrast, on-demand optogenetic excitation of glutamatergic neurons in the fastigial nucleus successfully inhibits hippocampal seizures. With this approach, even a single 50 ms pulse of light is able to significantly inhibit seizures.r On-demand optogenetic excitation of glutamatergic fastigial neurons either ipsilateral or contralateral to the seizure focus is able to inhibit seizures.r Selective excitation of glutamatergic nuclear neurons provides greater seizure inhibition than broadly exciting nuclear neurons without cell-type specificity.Abstract Temporal lobe epilepsy is the most common form of epilepsy in adults, but current treatment options provide limited efficacy, leaving as many as one-third of patients with uncontrolled seizures. Recently, attention has shifted towards more closed-loop therapies for seizure control, and on-demand optogenetic modulation of the cerebellar cortex was shown to be highly effective at attenuating hippocampal seizures. Intriguingly, both optogenetic excitation and inhibition of cerebellar cortical output neurons, Purkinje cells, attenuated seizures. The mechanisms by which the cerebellum impacts seizures, however, are unknown. In the present study, we targeted the immediate downstream projection of vermal Purkinje cells -the fastigial nucleus -in order to determine whether increases and/or decreases in fastigial output can underlie seizure cessation. Though Purkinje cell input to fastigial neurons is inhibitory, direct optogenetic inhibition of the fastigial nucleus had no effect on seizure duration. Conversely, however, fastigial excitation robustly attenuated hippocampal seizures. Seizure cessation was achieved at multiple stimulation frequencies, regardless of laterality relative to seizure focus, and even with single light pulses. Seizure inhibition was greater when selectively targeting glutamatergic fastigial neurons than when an approach that lacked cell-type specificity was used. Together, these results suggest Martha Streng received a BA in Neuroscience and Behaviour from Mount Holyoke College and a PhD in Neuroscience from the University of Minnesota, Twin Cities, where she studied the encoding of motor predictive and feedback information by Purkinje cells during online motor control tasks. Her current research focuses on the characterization of cerebellar circuitry and output channels in health and disease. that stimulating excitatory neurons in the fastigial nucleus may be a promising approach for therapeutic intervention in temporal lobe epilepsy.

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“…Unlike the anterior thalamus that is implicated in propagation of temporal lobe seizures, the midline thalamus can be within the seizure onset network in TLE that needs to be clarified in a larger cohort. With the widespread acceptance of robot-assisted sEEG investigation to localize epilepsies, electrophysiological sampling from the thalamus is feasible and maybe justifiable in selected patients where the demonstration of early thalamic recruitment can be used to improvise therapies (-like implanting responsive neurostimulation in the thalamus 18 ) that complement resection.…”

Section: Resultsmentioning

confidence: 99%

Early Ictal Recruitment of Midline Thalamus in Mesial Temporal Lobe Epilepsy

Romeo

Roach

Tóth

et al. 2019

Preprint

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word count -100 Running head-38 characters Manuscript -Introduction word count-239 Discussion word count -264 Complete manuscript word count-1369 References-18 AbstractThe causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 seconds) and early propagation (9-60 seconds). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure-induced in the hippocampus rapidly recruited the thalamus.Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.

show abstract

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Cited by 72 publications

References 24 publications

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy

Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

Early Ictal Recruitment of Midline Thalamus in Mesial Temporal Lobe Epilepsy

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