Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis

Wolf, Peter

doi:10.1016/j.yebeh.2015.01.009

Cited by 62 publications

(55 citation statements)

References 34 publications

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“…Similar potent peripheral stimulation in the range of 8-12 Hz and 1.5-2 mA is commonly used to elicit BOLD signal in dexmedetomidine sedated rodents. In patients affected by Touch Induced Seizures (TIS), the sensory stimulations that induce seizures are repetitive and last 5-20 seconds (Hsieh et al, 2011;Kanemoto et al, 2001;Sala-Padro et al, 2015;Wolf, 2015). To trigger the epileptic activity in our animals, we applied a similar somatosensory stimulation.…”

Section: Dexmedetomidine Induces Seizures In Response To Potent Stimulimentioning

confidence: 99%

Dexmedetomidine - commonly used in functional imaging studies - increases susceptibility to seizures in rats but not in wild type mice

Bortel

Yao²,

Shmuel³

2019

Preprint

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Functional MRI (fMRI) of the resting-state utilizes spontaneous fluctuations in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. For correct interpretation of spontaneous fluctuations and functional connectivity in the resting-state, it is important to characterize the neuronal mechanisms of fMRI in animal models. Animal studies of the evoked response and resting-state commonly use dexmedetomidine sedation. It has been demonstrated that dexmedetomidine combined with potent sensory stimuli is prone to inducing seizures in Sprague-Dawley (SD) rats. To characterize these seizures, here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings. We characterize the susceptibility to seizures as a function of time from the beginning of dexmedetomidine administration. We show that these seizures are associated with spatially extensive high-amplitude cerebral blood flow and blood oxygenation responses, prone to be misinterpreted as normal responses in functional imaging studies that do not use neurophysiological recordings. We demonstrate that such seizures are generated not only in SD rats but also in Long-Evans rats. In contrast, we did not observe any seizures in C57BL6 mice that were similarly sedated with dexmedetomidine and stimulated with similar potent stimuli. We conclude that caution should be practiced in experiments that combine the administration of potent stimuli with dexmedetomidine sedation because high-amplitude hemodynamic responses evoked by peripheral stimulations are possibly due to the induction of epileptic activity in the cortical brain area. We further conclude that the susceptibility to dexmedetomidine-induced seizures is species dependent.

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Section: Dexmedetomidine Induces Seizures In Response To Potent Stimulimentioning

confidence: 99%

Dexmedetomidine - commonly used in functional imaging studies - increases susceptibility to seizures in rats but not in wild type mice

Bortel

Yao²,

Shmuel³

2019

Preprint

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“…Reflex seizures are seizures elicited by specific sensory stimulation. These seizures may be triggered by various types of stimuli that are patient-specific (Panayiotopoulos, 2005;Sala-Padro et al, 2015;Striano et al, 2012;Wolf, 2015). In humans, reflex seizures can be induced by simple somatosensory stimulation, such as a cutaneous sensorial stimulus (Koepp et al, 2016;Loscher, 1999;Sarkisian, 2001;Wolf, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…These seizures may be triggered by various types of stimuli that are patient-specific (Panayiotopoulos, 2005;Sala-Padro et al, 2015;Striano et al, 2012;Wolf, 2015). In humans, reflex seizures can be induced by simple somatosensory stimulation, such as a cutaneous sensorial stimulus (Koepp et al, 2016;Loscher, 1999;Sarkisian, 2001;Wolf, 2015). Touch-based somatosensory-evoked seizures, termed Touch Induced Seizures (TIS), are associated with cortical hyper-excitability and are classified as reflex seizures induced by a simple stimulus (Sala-Padro et al, 2015;Striano et al, 2012;Wolf, 2015).…”

Section: Introductionmentioning

confidence: 99%

A Rat Model of Somatosensory-Evoked Reflex Seizures Induced by Peripheral Stimulation

Bortel

Yao

Shmuel

2018

Preprint

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Objective:We introduce a novel animal model of somatosensory stimulation-induced reflex seizures which generates focal seizures without causing damage to the brain.Methods: Specifically, we electrically stimulated digits or forepaws of adult rats sedated with dexmedetomidine while imaging cerebral blood volume and recording neurophysiological activity in cortical area S1FL. For the recordings, we either inserted a linear probe into the D3 digit representation or we performed surface electrocorticography (ECoG) recordings.Results: Peripheral stimulation of a digit or the forepaw elicited seizures that were followed by a refractory period with decreased neuronal activity, or another seizure or a normal response. LFP amplitudes in response to electrical pulses during the seizures (0.28 ± 0.03 mV) were higher than during normal evoked responses (0.25 ± 0.05 mV) and refractory periods (0.2 ± 0.08 mV). Seizures generated during the stimulation period showed prolonged after-discharges that were sustained for 20.9±1.9 s following the cessation of the stimulus. High-frequency oscillations were observed prior to and during the seizures, with amplitudes higher than those associated with normal evoked responses. The seizures were initially focal. Optical imaging of the cerebral blood volume response showed that they propagated from the onset zone to adjacent cortical areas, beyond the S1FL representation of the stimulated digit or forepaw. The spatial extent during seizures was on average 1.74 times larger during the stimulation and 4.1 times following its cessation relative to normal evoked responses. Seizures were recorded not only by probes inserted into cortex but also with ECoG arrays (24.1±5.8 seizures per rat) placed over the dura matter, indicating that the seizures were not induced by damage caused by inserting the probes to cortex. Stimulation of the forepaw elicited more seizures (18.8±8.5 seizures per rat) than stimulation of a digit (1.7±0.7). Unlike rats sedated with dexmedetomidine, rats anesthetized with urethane showed no seizures, indicating that the seizures may depend on the use of the mild sedative dexmedetomidine.Significance: Our proposed animal model generates seizures induced by electrical sensory stimulation free of artifacts and brain damage. It can be used for studying the mechanisms underlying the generation and propagation of reflex seizures and for evaluating antiepileptic drugs.

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“…Reflex seizures have been described with various triggers and etiologies. 1,2 Author contributions G.C. Fernandes: drafting/revising the manuscript, study concept or design, accepts responsibility for conduct of research and final approval, acquisition of data.…”

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confidence: 99%

Proprioceptive-induced (stimulus-sensitive) reflex seizures

et al. 2020

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Proprioceptive-induced (stimulus-sensitive) reflex seizuresThis information is current as of January 13, 2020 Services Updated Information & http://n.neurology.org/content/94/2/89.full including high resolution figures, can be found at: References http://n.neurology.org/content/94/2/89.full#ref-list-1 This article cites 2 articles, 0 of which you can access for free at: Subspecialty Collections http://n.neurology.org/cgi/collection/video__eeg_use_in_epilepsy Video/ EEG use in epilepsy http://n.neurology.org/cgi/collection/epilepsy_semiology Epilepsy semiology http://n.neurology.org/cgi/collection/eeg_ EEG http://n.neurology.org/cgi/collection/clinical_neurology_examination Clinical neurology examination http://n.neurology.org/cgi/collection/all_education All Education following collection(s):This article, along with others on similar topics, appears in the

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Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis

Cited by 62 publications

References 34 publications

Dexmedetomidine - commonly used in functional imaging studies - increases susceptibility to seizures in rats but not in wild type mice

Dexmedetomidine - commonly used in functional imaging studies - increases susceptibility to seizures in rats but not in wild type mice

A Rat Model of Somatosensory-Evoked Reflex Seizures Induced by Peripheral Stimulation

Proprioceptive-induced (stimulus-sensitive) reflex seizures

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