Driving status of patients with generalized spike–wave on EEG but no clinical seizures

Antwi, Prince; Atac, Ece; Ryu, Jun Hwan; Arencibia, Christopher A.; Tomatsu, Shiori; Saleem, Neehan; Wu, Jia; Crowley, Michael J.; Banz, Barbara C.; Vaca, Federico E.; Krestel, Heinz; Blumenfeld, Hal

doi:10.1016/j.yebeh.2018.11.031

Cited by 24 publications

(25 citation statements)

References 92 publications

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“…In the frozen model of CD, SWDs were also detected at a higher frequency with longer durations during slow-wave sleep ( Williams et al, 2016 ). The SWD pattern was similar to that of spontaneous SWDs that have been observed in absence epilepsy and similar to the spike-wave that occurs in human absence seizures and electrical status epilepticus ( Coenen and Van Luijtelaar, 2003 ; Sun et al, 2016 ; Antwi et al, 2019 ). However, it is still unclear whether the mechanism of epileptogenesis is associated with SWDs.…”

Section: Discussionsupporting

confidence: 78%

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Yang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasing studies have implicated innate immunity in CD with epilepsy. However, it is unclear whether innate immune factors induce epileptogenic CD. Here, we injected recombinant human high mobility group box 1 (rHMGB1) into embryonic rat ventricles to determine whether rHMGB1 can induce epileptogenic CD with pathophysiological characteristics similar to those of human CD. Compared with controls and 0.1 μg rHMGB1-treated rats, the cortical organization was severely disrupted in the 0.2 μg rHMGB1-treated rats, and microgyria and heterotopia also emerged; additionally, disoriented and deformed neurons were observed in the cortical lesions and heterotopias. Subcortical heterotopia appeared in the white matter and the gray–white junction of the 0.2 μg rHMGB1-treated rats. Moreover, there was decreased number of neurons in layer V–VI and an increased number of astrocytes in layer I and V of the cortical lesions. And the HMGB1 antagonist dexmedetomidine alleviated the changes induced by rHMGB1. Further, we found that TLR4 and NF-κB were increased after rHMGB1 administration. In addition, the excitatory receptors, N-methyl-D-aspartate receptor 1 (NR1), 2A (NR2A), and 2B (NR2B) immunoreactivity were increased, and immunoreactivity of excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2) were reduced in 0.2 μg rHMGB1-treated rats compared with controls. While there were no differences in the glutamic acid decarboxylase 65/67 (GAD65/67) immunoreactivity between the two groups. These results indicate that the excitation of cortical lesions was significantly increased. Furthermore, electroencephalogram (EEG) showed a shorter latency of seizure onset and a higher incidence of status epilepticus in the 0.2 μg rHMGB1-treated rats; the frequency and amplitude of EEG were higher in the treated rats than controls. Intriguingly, spontaneous electrographic seizure discharges were detected in the 0.2 μg rHMGB1-treated rats after 5 months of age, and spike-wave discharges of approximately 8 Hz were the most significantly increased synchronous propagated waves throughout the general brain cortex. Taken together, these findings indicate that rHMGB1 exposure during pregnancy could contribute to the development of epileptogenic CD, which mimicked some pathophysiological characteristics of human CD.

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Section: Discussionsupporting

confidence: 78%

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Yang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…In the frozen model of CD, SWDs were also detected, were more frequent and had longer durations during slow-wave sleep [30]. The SWD pattern was similar to that of the spontaneous SWDs that have been observed in absence epilepsy and similar to the spike wave that occurs in human absence seizures and electrical status epilepticus [29,31,32]. However, it is still unclear whether the mechanism of epileptogenesis is associated with SWDs.…”

Section: Spike-wave Discharges In CDsupporting

confidence: 52%

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimicked the Pathophysiology of Human Cortical Dysplasia

Yang

Zhang

Wang

et al. 2020

Preprint

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Background Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasingly, innate immunity is involved in CD with epilepsy. However, it is unclear whether innate immune factors contribute to induce epileptogenic CD. Here, we injected recombinant human HMGB1 (rHMGB1) into the embryonic rat ventricle to determine whether rHMGB1 can induce epileptogenic CD with pathophysiological characteristics similar to those of human CD.Methods At gestational day 14.5, rHMGB1 was injected into the ventricles of Sprague Dawley (SD) rat embryos. At 2 months postnatal, the effects of rHMGB1 on cortex construction were examined by Nissl staining; the alterations of nerve tissue were detected using immunostaining. At 3 months postnatal, the susceptibility and severity of pilocarpine-induced seizures and the spontaneous epileptic discharges were evaluated by EEG. Open-field tests, novel object recognition tests, and Morris water maze tests were performed to observe the behavior of rHMGB1-treated rats.Results The results showed cortical organization was severely disrupted in the rHMGB1-treated rats, and microgyria and heterotopia also emerged; additionally, disoriented neurons, dysmorphic neurons, and dysplastic neurons were found in the cortical lesions and heterotopias. Subcortical heterotopia also appeared in the white matter and the gray-white junction of the rHMGB1-treated rats. Moreover, the numbers of neurons and astrocytes were increased in the cortical lesions; the neuronal dendrites were thickened, randomly oriented, and frequently crossed each other. Moreover, the immunoreactivity of NR2A, NR2B, NR1, GAD65/67, EAAT1 and EAAT2 indicated that the excitation of cortical lesions and heterotopia were significantly increased. Furthermore, EEG showed more susceptibility and severity of seizures in rHMGB1-treatment rats compared with the control rats. Intriguingly, spontaneous nonepileptic seizure discharges were also detected in the rHMGB1-treated rats after 5 months of age, and spike-wave discharges of approximately 8 Hz were the most significantly increased synchronously propagated waves throughout the general brain cortex.Conclusions These results indicated that rHMGB1 exposure during pregnancy can modify the cerebral structure of offspring, which results in increased susceptibility to seizures and mimics the pathophysiological characteristics of human CD. Those results suggested that HMGB1 upregulation resulting from various insults could contribute to the development of epileptogenic CD during pregnancy.

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“…The approach described here may help solve an important dilemma confronting people with generalized epilepsy who have apparently stopped having clinical seizures either due to outgrowing them or due to effective medications, but where the EEG still shows frequent GEDs . The uncertain risk of motor vehicle collisions among people with epilepsy merits restrictions of driving privileges to protect them and the public.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence of effective seizure control is the main criterion used to allow driving in most parts of the United States . Despite a consensus regarding the need for a seizure‐free period prior to driving, there is little agreement regarding the necessary duration of such periods . There is also uncertainty regarding whether a reliable aura or warning should be a favorable modifier to enable driving .…”

Section: Introductionmentioning

confidence: 99%

“…One important problem is the many patients who are clinically seizure‐free yet have epileptiform discharges on electroencephalography (EEG) including GEDs. These epileptiform discharges, with no obvious clinical sequelae, pose a challenge to driver licensing authorities, as well as to clinicians and their patients . Despite not being perceived by patients, subclinical epileptiform discharges might be accompanied by transient cognitive impairments, and their effect on driving and potential public safety risk is uncertain …”

Section: Introductionmentioning

confidence: 99%

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Realistic driving simulation during generalized epileptiform discharges to identify electroencephalographic features related to motor vehicle safety: Feasibility and pilot study

et al. 2019

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Objective: Generalized epileptiform discharges (GEDs) can occur during seizures or without obvious clinical accompaniment. Motor vehicle driving risk during apparently subclinical GEDs is uncertain. Our goals were to develop a feasible, realistic test to evaluate driving safety during GEDs, and to begin evaluating electroencephalographic (EEG) features in relation to driving safety. Methods: Subjects were aged ≥15 years with generalized epilepsy, GEDs on EEG, and no clinical seizures. Using a high-fidelity driving simulator (miniSim) with simultaneous EEG, a red oval visual stimulus was presented every 5 minutes for baseline testing, and with each GED. Participants were instructed to pull over as quickly and safely as possible with each stimulus. We analyzed driving and EEG signals during GEDs.Results: Nine subjects were tested, and five experienced 88 GEDs total with mean duration 2.31 ± 1.89 (SD) seconds. Of these five subjects, three responded appropriately to all stimuli, one failed to respond to 75% of stimuli, and one stopped driving immediately during GEDs. GEDs with no response to stimuli were significantly longer than those with appropriate responses (8.47 ± 3.10 vs 1.85 ± 0.69 seconds, P < .001). Reaction times to stimuli during GEDs were significantly correlated with GED duration (r = 0.30, P = .04). In addition, EEG amplitude was greater for GEDs with no response to stimuli than GEDs with responses, both for overall root mean square voltage amplitude (66.14 μV vs 52.99 μV, P = .02) and for fractional power changes in the frequency range of waves (P < .05) and spikes (P < .001). Significance: High-fidelity driving simulation is feasible for investigating driving behavior during GEDs. GEDs with longer duration and greater EEG amplitude showed more driving impairment. Future work with a large sample size may ultimately enable classification of GED EEG features to predict individual driving risk. K E Y W O R D Sabsence seizures, consciousness, driving, EEG, epilepsy, spike-wave discharges 20 | COHEN Et al.

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Driving status of patients with generalized spike–wave on EEG but no clinical seizures

Cited by 24 publications

References 92 publications

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimicked the Pathophysiology of Human Cortical Dysplasia

Realistic driving simulation during generalized epileptiform discharges to identify electroencephalographic features related to motor vehicle safety: Feasibility and pilot study

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