Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation

Doležalová, Irena; Kunst, Jonas; Kojan, Martin; Chrastina, Jan; Baláž, Marek; Brázdil, Milan

doi:10.1016/j.ebr.2019.100344

Cited by 6 publications

(4 citation statements)

References 12 publications

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“…In fact, only 16% of patients report seizure-free interval of at least 6 months, 35.5% develop device-related serious adverse side effects, 37.3% report depression, and 27.3% memory impairment. 47,48 Callosotomies were previously used to treat refractory generalized epilepsy but are less common in current clinical practice. Selective lesions of the callosal fibers that connect the seizure focus for example through the development of noninvasive focused ultrasound and deep brain stimulation to modulate cortico-cortical projections could reduce generalized tonic-clonic seizures and sudden unexpected death in epilepsy (SUDEP) and serve as alternatives to thalamic stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, anterior thalamic deep brain stimulation is performed on patients with intractable epilepsy, but it is not always effective. In fact, only 16% of patients report seizure‐free interval of at least 6 months, 35.5% develop device‐related serious adverse side effects, 37.3% report depression, and 27.3% memory impairment 47,48 . Callosotomies were previously used to treat refractory generalized epilepsy but are less common in current clinical practice.…”

Section: Discussionmentioning

confidence: 99%

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Distinct Roles of Rodent Thalamus and Corpus Callosum in Seizure Generalization

Brodovskaya

Batabyal

Shiono

et al. 2022

Annals of Neurology

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Objective Bilateral synchronous cortical activity occurs during sleep, attention, and seizures. Canonical models place the thalamus at the center of bilateral cortical synchronization because it generates bilateral sleep spindle oscillations and primarily generalized absence seizures. However, classical studies suggest that the corpus callosum mediates bilateral cortical synchronization. Methods We mapped the spread of right frontal lobe‐onset, focal to bilateral seizures in mice and modified it using chemo and optogenetic suppression of motor thalamic nucleus and corpus callosotomy. Results Seizures from the right cortex spread faster to the left cortex than to the left thalamus. The 2 thalami have minimal monosynaptic commissural connections compared to the massive commissure corpus callosum. Chemogenetic and closed‐loop optogenetic inhibition of the right ventrolateral thalamic nucleus did not alter inter‐hemispheric seizure spread. However, anterior callosotomy delayed bilateral seizure oscillations. Interpretation Thalamocortical oscillations amplify focal onset motor seizures, and corpus callosum spreads them bilaterally. ANN NEUROL 2022;91:682–696

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Distinct Roles of Rodent Thalamus and Corpus Callosum in Seizure Generalization

Brodovskaya

Batabyal

Shiono

et al. 2022

Annals of Neurology

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“…Most patients showed improvements in anxiety, attention, and executive function compared to baseline. Though, outside of that clinical trial, there has been a reported case of persistent psychiatric side effects during ANT DBS and following discontinuation of ANT DBS (Doležalová et al, 2019 ). For patients with intractable epilepsy receiving vagus nerve stimulation (VNS), the impact on mood appears to be favorable; VNS is an FDA-approved therapy for treatment-resistant depression (Aaronson et al, 2017 ; Chan et al, 2018 ; Elger et al, 2000 ).…”

Section: Rigorous Practices: Confounding Factors and Recommendations For Experimental Designsmentioning

confidence: 99%

Invasive Electrophysiology for Circuit Discovery and Study of Comorbid Psychiatric Disorders in Patients With Epilepsy: Challenges, Opportunities, and Novel Technologies

Balzekas

Sladky

Nejedlý

et al. 2021

Front. Hum. Neurosci.

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Intracranial electroencephalographic (iEEG) recordings from patients with epilepsy provide distinct opportunities and novel data for the study of co-occurring psychiatric disorders. Comorbid psychiatric disorders are very common in drug-resistant epilepsy and their added complexity warrants careful consideration. In this review, we first discuss psychiatric comorbidities and symptoms in patients with epilepsy. We describe how epilepsy can potentially impact patient presentation and how these factors can be addressed in the experimental designs of studies focused on the electrophysiologic correlates of mood. Second, we review emerging technologies to integrate long-term iEEG recording with dense behavioral tracking in naturalistic environments. Third, we explore questions on how best to address the intersection between epilepsy and psychiatric comorbidities. Advances in ambulatory iEEG and long-term behavioral monitoring technologies will be instrumental in studying the intersection of seizures, epilepsy, psychiatric comorbidities, and their underlying circuitry.

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“…One report describing a patient with persistent psychiatric adverse events contradicts this belief. 43 Mood disturbances or memory problems observed only in a blinded phase of the SANTE trial may be related to overstimulation of the ANT and a lesional (microthalamotomy) effect. 16 Monopolar stimulation using relatively high stimulation parameters (especially voltage) in an early postoperative phase may explain this transient subjective mood and memory problems.…”

Section: Cognitive and Emotional Sequelae Of Ant Dbsmentioning

confidence: 99%

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

Sobstyl

Stapińska-Syniec

Iwański

et al. 2021

J Neurol Surg A Cent Eur Neurosurg

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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.

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Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation

Cited by 6 publications

References 12 publications

Distinct Roles of Rodent Thalamus and Corpus Callosum in Seizure Generalization

Distinct Roles of Rodent Thalamus and Corpus Callosum in Seizure Generalization

Invasive Electrophysiology for Circuit Discovery and Study of Comorbid Psychiatric Disorders in Patients With Epilepsy: Challenges, Opportunities, and Novel Technologies

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

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