Seizures induced in electroconvulsive therapy as a human epilepsy model: A comparative case study

Pottkämper, Julia; Verdijk, Joey; Hofmeijer, Jeannette; Waarde, Jeroen A. van; Putten, Michel Johannes Antonius Maria van

doi:10.1002/epi4.12532

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…In this study, the examined ECT-induced seizures will be part of the treatment of patients with a severe depressive episode. The postictal period in ECT-induced seizures and spontaneous seizures in epilepsy patients are clinically and electrographically comparable [ 4 ]. Clinical similarities include sensory, motor, or memory deficits, impaired cognition, headache, delirium, or psychosis [ 5 – 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Patients with epilepsy suffer from reoccurring unpredictable seizures. The postictal state in patients suffering epilepsy is strikingly similar to those of ECT patients [ 4 ]. In patients with epilepsy, postictal phenomena may present as unresponsiveness, sensory, motor, or memory deficits, impaired cognition, headache, delirium, or psychosis, which may last several minutes to hours [ 5 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

Verdijk

Pottkämper

Verwijk

et al. 2022

Trials

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Background Postictal phenomena as delirium, headache, nausea, myalgia, and anterograde and retrograde amnesia are common manifestations after seizures induced by electroconvulsive therapy (ECT). Comparable postictal phenomena also contribute to the burden of patients with epilepsy. The pathophysiology of postictal phenomena is poorly understood and effective treatments are not available. Recently, seizure-induced cyclooxygenase (COX)-mediated postictal vasoconstriction, accompanied by cerebral hypoperfusion and hypoxia, has been identified as a candidate mechanism in experimentally induced seizures in rats. Vasodilatory treatment with acetaminophen or calcium antagonists reduced postictal hypoxia and postictal symptoms. The aim of this clinical trial is to study the effects of acetaminophen and nimodipine on postictal phenomena after ECT-induced seizures in patients suffering major depressive disorder. We hypothesize that (1) acetaminophen and nimodipine will reduce postictal electroencephalographic (EEG) phenomena, (2) acetaminophen and nimodipine will reduce magnetic resonance imaging (MRI) measures of postictal cerebral hypoperfusion, (3) acetaminophen and nimodipine will reduce clinical postictal phenomena, and (4) postictal phenomena will correlate with measures of postictal hypoperfusion. Methods We propose a prospective, three-condition cross-over design trial with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design). Thirty-three patients (age > 17 years) suffering from a depressive episode treated with ECT will be included. Randomly and alternately, single doses of nimodipine (60 mg), acetaminophen (1000 mg), or water will be given two hours prior to each ECT session with a maximum of twelve sessions per patient. The primary outcome measure is ‘postictal EEG recovery time’, expressed and quantified as an adapted version of the temporal brain symmetry index, yielding a time constant for the duration of the postictal state on EEG. Secondary outcome measures include postictal cerebral perfusion, measured by arterial spin labelling MRI, and the postictal clinical ‘time to orientation’. Discussion With this clinical trial, we will systematically study postictal EEG, MRI and clinical phenomena after ECT-induced seizures and will test the effects of vasodilatory treatment intending to reduce postictal symptoms. If an effect is established, this will provide a novel treatment of postictal symptoms in ECT patients. Ultimately, these findings may be generalized to patients with epilepsy. Trial registration Inclusion in SYNAPSE started in December 2019. Prospective trial registration number is NCT04028596 on the international clinical trial register on July 22, 2019.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

Verdijk

Pottkämper

Verwijk

et al. 2022

Trials

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“…Stimulus charge was determined based on either the half‐age method (i.e., in case of BL electrode placement) or dosage titration (i.e., with right or left UL electrode placement). In the case of severe postictal confusion, midazolam 2–5 mg was provided intravenously 17 . A detailed overview of the study protocol is given elsewhere 20,24 …”

Section: Methodsmentioning

confidence: 99%

“…In ECT, mainly as treatment for severe depression, focal to bilateral tonic–clonic seizures are elicited by using an electrical stimulus, applied through two electrodes on a patient's head under anesthesia and with proper muscle relaxation 9,16 . Several characteristics of ECT‐induced seizures, such as the type of ictal discharges and postictal electroencephalography (EEG) and clinical symptoms, appear similar to those of generalized seizures in epilepsy patients 17 . This suggests that findings in studies that explore ECT‐induced seizure characteristics, such as duration, and cerebral perfusion may be extrapolated to patients with epilepsy.…”

Section: Introductionmentioning

confidence: 99%

“…9,16 Several characteristics of ECT-induced seizures, such as the type of ictal discharges and postictal electroencephalography (EEG) and clinical symptoms, appear similar to those of generalized seizures in epilepsy patients. 17 This suggests that findings in studies that explore ECT-induced seizure characteristics, such as duration, and cerebral perfusion may be extrapolated to patients with epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy‐induced seizures

Pottkämper,

Verdijk,

Aalbregt

et al. 2023

Epilepsia

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ObjectivePostictal symptoms may result from cerebral hypoperfusion which is possibly a consequence of seizure‐induced vasoconstriction. Longer seizures have previously been shown to cause more severe postictal hypoperfusion in rats and epilepsy patients. We studied cerebral perfusion after generalized seizures elicited by electroconvulsive therapy (ECT) and its relation to seizure duration.MethodsPatients with a major depressive episode who underwent ECT were included. During treatment, 21‐channel continuous electroencephalogram (EEG) was recorded. Arterial spin labeling magnetic resonance imaging (ASL‐MRI) scans were acquired before the ECT‐course (baseline) and approximately one hour after an ECT‐induced seizure (postictal) to quantify global and regional gray matter cerebral blood flow (CBF). Seizure duration was assessed from the period of epileptiform discharges on the EEG. Healthy controls were scanned twice to assess test‐retest variability. We performed hypothesis‐driven Bayesian analyses to study the relation between global and regional perfusion changes and seizure duration.ResultsTwenty‐four patients and twenty‐seven healthy controls were included. Changes in postictal global and regional CBF were correlated with seizure duration. In patients with longer seizure durations, global decrease in CBF reached values up to 28 ml/100g/min. Regional reductions in CBF were most prominent in the inferior frontal gyrus, cingulate gyrus, and insula (up to ~35 ml/100g/min). In patients with shorter seizures global and regional perfusion increased (up to ~20 ml/100g/min). These perfusion changes were larger than changes observed in healthy controls, with a maximum median global CBF increase of 12 ml/100g/min and a maximum median global CBF decrease of 20 ml/100g/min.SignificanceSeizure duration is a key factor determining postictal perfusion changes. In future studies, seizure duration needs to be considered as confounding factor due to its opposite effect on postictal perfusion. .

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Exploring postictal recovery with acetaminophen or nimodipine: A randomized‐controlled crossover trial

Pottkämper,

Verdijk,

Stuiver

et al. 2024

Ann Clin Transl Neurol

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ObjectiveThe postictal state is underrecognized in epilepsy. Animal models show improvement of postictal symptoms and cerebral perfusion with acetaminophen or nimodipine. We studied the effects of acetaminophen or nimodipine on postictal electroencephalographic (EEG) recovery, clinical reorientation, and hypoperfusion in patients with ECT‐induced seizures.MethodsIn this prospective clinical trial with three‐condition randomized crossover design, study interventions were administered orally 2 h before ECT sessions (1000 mg acetaminophen, 60 mg nimodipine, or a placebo condition). Primary outcome measure was the speed of postictal EEG recovery. Secondary outcomes were the extent of postictal EEG recovery, clinical reorientation time, and postictal cerebral blood flow as assessed by perfusion‐weighted MRI. Bayesian generalized mixed‐effects models were applied for analyses.ResultsWe included 300 seizures, postictal EEGs, and reorientation time values, and 76 MRI perfusion measures from 33 patients (median age 53 years, 19 female). Pretreatment with acetaminophen or nimodipine was not associated with change in speed of EEG recovery compared to placebo (1.13 [95%CI 0.92, 1.40] and 1.07 [95%CI 0.87, 1.31], respectively), nor with the secondary outcomes. No patient reached full EEG recovery at 1 h post‐seizure, despite clinical recovery in 89%. Longer seizures were associated with slower EEG recovery and lower postictal perfusion. Nimodipine altered regional perfusion in the posterior cortex.InterpretationPretreatment with acetaminophen or nimodipine did not alleviate symptoms and signs of the postictal state. Systematic study of the postictal state after ECT‐induced seizures is feasible.

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Seizures induced in electroconvulsive therapy as a human epilepsy model: A comparative case study

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 51 publications

Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)

Changes in postictal cerebral perfusion are related to the duration of electroconvulsive therapy‐induced seizures

Exploring postictal recovery with acetaminophen or nimodipine: A randomized‐controlled crossover trial

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