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Seminars in Neurology Dec 2020Acute provoked seizures, also known as acute symptomatic seizures, occur secondary to a neurological or systemic precipitant, commonly presenting as a first-time... (Review)
Review
Acute provoked seizures, also known as acute symptomatic seizures, occur secondary to a neurological or systemic precipitant, commonly presenting as a first-time seizure. In this article, we will discuss etiology, emergent protocols, medical work-up, initial treatment, and management of these seizures. The definitions, classifications, and management of convulsive status epilepticus and nonconvulsive status epilepticus in an acute setting will also be reviewed.
Topics: Anticonvulsants; Humans; Seizures; Status Epilepticus
PubMed: 33155185
DOI: 10.1055/s-0040-1719075 -
Epilepsia Open Dec 2022Despite introduction of several antiseizure medications over the past two decades, treatment options for childhood absence epilepsy (CAE) and juvenile absence epilepsy... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Despite introduction of several antiseizure medications over the past two decades, treatment options for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) remain limited. We report the innovative adaptive design of an ongoing phase 2/3 trial to evaluate efficacy, safety, and tolerability of brivaracetam (BRV) monotherapy in patients 2-25 years of age with CAE or JAE.
METHODS
N01269 (ClinicalTrials.gov: NCT04666610; start: July 2021; expected completion: 2024) is a randomized, dose-finding and confirmatory, double-blind, placebo-controlled, parallel-group, multicenter trial. The trial consists of a dose-selection and assessment for futility stage, followed by an optimal-dose stage after interim analysis. Both stages include an up to 2-week screening period, a 2-week placebo-controlled period, and an 11-week active treatment period (10 weeks of initial treatment followed by a 24-hour electroencephalogram [EEG] and an additional week of active treatment for 24-hour EEG assessment). Patients who are absence seizure-free will enter an up to 4-week randomized withdrawal period. Efficacy assessments will be based on 24-hour EEG and seizure diaries.
SIGNIFICANCE
This two-stage adaptive trial design allows investigation of two potentially efficacious BRV doses, where one dose is dropped in favor of the other dose with a better benefit-risk profile. This allows for a combined phase 2 dose-finding and phase 3 confirmatory efficacy trial, which reduces the number of patients needed to be recruited and reduces trial duration. A randomized withdrawal period is included to evaluate sustainability of treatment effect over time and to allow for placebo control while minimizing placebo exposure. Use of EEG capture in addition to seizure diaries offers a robust mechanism of detecting seizure activity and measuring treatment effect. Positive efficacy and safety/tolerability data may support the use of BRV as monotherapy for CAE or JAE, providing another treatment option and representing long-delayed progress in the treatment of absence seizures in these populations.
Topics: Humans; Epilepsy, Absence; Anticonvulsants; Drug Therapy, Combination; Treatment Outcome; Seizures
PubMed: 35844134
DOI: 10.1002/epi4.12628 -
Frontiers in Neural Circuits 2023Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic...
Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O in N) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.
Topics: Mice; Animals; Minocycline; Seizures; Microglia; Brain; Hypoxia
PubMed: 37035503
DOI: 10.3389/fncir.2023.1006424 -
Journal of Child Neurology Aug 2022To determine the nature of staring spells and factors distinguishing epileptic from nonepileptic staring spells, we studied the clinical and demographic features of...
OBJECTIVE
To determine the nature of staring spells and factors distinguishing epileptic from nonepileptic staring spells, we studied the clinical and demographic features of children with staring spells referred to a regional new-onset seizure clinic.
STUDY DESIGN
Our retrospective chart review encompassed 2818 consecutive patients evaluated in the new-onset seizure clinic between September 22, 2015, and March 19, 2018. We identified 121 patients with newly presenting staring spells.
RESULTS
Sixty-two of 121 (51%) children were diagnosed with nonepileptic staring spells and 59 (49%) with epileptic seizures (24 with absence epilepsy, 35 with focal epilepsy). Patients with nonepileptic staring spells were younger (4.8 vs 7.1 years, = .001) and more likely to have developmental delay ( = .005) than the seizure group. There was an 8.9-month delay on average from the onset of staring spells to the new-onset seizure clinic visit. The emergency department was a referral source for 80% (28/35) of focal seizures. In children with focal seizures, the staring spells typically lasted >1minute (29/35, 83%), whereas only 19 of 62 (31%) of children with nonepileptic staring spells had events lasting this long ( = .04). All children had a routine electroencephalography (EEG) on the day of new-onset seizure clinic visit. EEG was diagnostic in 100% (24/24) of absence seizures and 51% (18/35) of focal seizures.
CONCLUSIONS
In children presenting with staring spells, the differential diagnosis of epileptic staring spells vs nonepileptic staring spells can be made by history and routine EEG. Staring was as likely to be epileptic as nonepileptic spells. Younger children with developmental delay were more likely to have nonepileptic events. Our simple approach based on event duration, postictal symptoms, and EEG allowed identification of epileptic staring on first visit to new-onset seizure clinic but requires validation in future prospective studies including long-term video EEG monitoring and follow-up.
Topics: Child; Electroencephalography; Epilepsy, Absence; Humans; Mental Disorders; Retrospective Studies; Seizures
PubMed: 35746887
DOI: 10.1177/08830738221103090 -
Medicina Clinica Mar 2023Idiopathic generalized epilepsies (IGI) are an electroclinical syndrome that includes four subsyndromes according to the ILAE 2017 classification. The long-term...
INTRODUCTION
Idiopathic generalized epilepsies (IGI) are an electroclinical syndrome that includes four subsyndromes according to the ILAE 2017 classification. The long-term prognosis of these syndromes is uncertain due to the scarcity and heterogeneity of the studies. The objective of this study is to analyze the long-term prognosis of these syndromes, pharmacological treatment and the seizure recurrence.
METHOD
Observational and retrospective study of a serie of patients diagnosed with EGI. Epidemiological variables, pharmacological treatment, freedom of seizures and recurrence after withdrawal of treatment were collected.
RESULTS
We included 101 patients, the majority women (56.4%), with a median evolution of epilepsy of 17 years (interquartile range: 7-31). The most frequent syndrome was juvenile myoclonic epilepsy (46.5%), followed by epilepsy with generalized tonic-clonic seizures alone (25.7%), juvenile absence epilepsy (13.9%) and childhood absence epilepsy (13.9%). The 71.29% were on monotherapy and 20.79% on polytherapy, with significant differences between the different syndromes (P=.001). The most widely used drug was valproic acid. 39.6% presented seizure remission at 5 years, but we did not observe significant differences between the different syndromes (P=.982). The recurrence rate was 71.4% after withdrawal of treatment.
CONCLUSION
Juvenile myoclonic epilepsy was the most frequent subtype of IGE. We observed significant differences in terms of polytherapy in the different syndromes, although not in the rates of remission of seizures at one year and at five years. The majority of patients with treatment withdrawal relapsed.
Topics: Humans; Female; Child; Myoclonic Epilepsy, Juvenile; Retrospective Studies; Epilepsy, Generalized; Epilepsy, Absence; Seizures; Syndrome; Anticonvulsants; Electroencephalography
PubMed: 36030098
DOI: 10.1016/j.medcli.2022.06.019 -
Epilepsy & Behavior : E&B Mar 2022To assess the occurrence of sleep disorders (SD) and attention deficit hyperactivity disorder (ADHD) symptoms in children with typical absence seizures (TAS) compared to... (Observational Study)
Observational Study
OBJECTIVE
To assess the occurrence of sleep disorders (SD) and attention deficit hyperactivity disorder (ADHD) symptoms in children with typical absence seizures (TAS) compared to control children and to evaluate the impact of epilepsy-related factors on sleep and attention in children with TAS.
METHODS
The Sleep Disturbance Scale for Children (SDSC) and the ADHD rating scale were filled in by parents of a cohort composed by 82 children aged from 5 to 15.6 years, 49% of boys (41 with TAS with a syndromic diagnosis of childhood absence epilepsy and 41 controls). For children with TAS, the Pediatric Epilepsy Side Effects Questionnaire was completed. Statistical analyses were conducted in order to compare sleep and attention scores between groups. In children with TAS, a correlation was computed between these scores. Logistics regression models were conducted to identify predictors of excessive diurnal sleepiness and inattention in children with TAS.
RESULTS
Compared to controls, children with TAS had higher total scores for subjective sleep (mean 42.9 vs 38.3, p = 0.05) and attention disorders (mean 16.8 vs 11.6, p = 0.01), especially for excessive diurnal sleepiness (mean 3.9 vs 3.2, p = 0.02) and inattention (mean 9.3 vs 5.6, p = 0.003) components. In children with TAS, sleep problems were significantly under-reported by parents. Sleep disorders symptoms as breathing-related sleep disturbance, excessive diurnal sleepiness or naps at or after 7 years of age were reported. Subjective sleep and attention disorders were significantly correlated (r = 0.43, p = 0.01). Subjective excessive diurnal sleepiness may be the result of a polytherapy (p = 0.05) or a side effect of anti-seizure medication (ASM) (p = 0.03) but children without medication side effects also reported subjective SD. In children with TAS, the risk of inattention symptoms was increased in boys (p = 0.02), with a high BMI (p = 0.05), or with ASM side effects (p = 0.03).
CONCLUSIONS
This study demonstrates that children with TAS are at risk of sleep and attention disorder symptoms. If attention disorders in a context of epilepsy are now widely assessed and identified, sleep disorders are still under-estimated. An accurate identification and management of sleep disorders could improve academic performances, quality of life, and seizure management in children with TAS.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Epilepsy, Absence; Humans; Male; Quality of Life; Seizures; Sleep; Sleep Wake Disorders; Surveys and Questionnaires
PubMed: 35085916
DOI: 10.1016/j.yebeh.2021.108513 -
Seizure May 2021To investigate whether the parameters of EEG microstates changed before and after an absence seizure episode.
OBJECTIVE
To investigate whether the parameters of EEG microstates changed before and after an absence seizure episode.
METHODS
AE patients with a current high frequency of seizures were included (n=21). Each included subject underwent a two-hour and 19-channel video EEG examination. Five epochs of 10-second EEG data in interictal, pre-seizure, and post-seizure states were collected from each AE patient. Five 10-second resting-state EEG epochs from sex- and age-matched HCs who reported no history of neurological or psychiatric disorders and visited the hospital for routine physical examinations were collected. Microstate analysis and source localization of microstates were performed using the LORETA KEY tool.
RESULTS
Compared with the resting-state EEGs of HCs, the interictal EEGs of AE patients showed a higher relative transition rate from microstates B to D (p<0.05). From interictal to pre-seizure EEG, the total time ratio of microstate C and the occurrence of microstate B decreased significantly, while the duration of microstate B increased significantly (p<0.05). Compared with pre-seizure EEGs, microstate C in post-seizure EEGs showed a significantly downregulated total time percentage and occurrence (p<0.05). The source localization of each microstate in each condition also varied and showed spatial recovery tends from pre- to post-seizure states.
CONCLUSION
Altered EEG microstate dynamics exist between inter-ictal EEGs of AE patients and resting-state EEGs of HCs and between pre- and post-seizure EEGs in AE patients. The EEG microstates of epileptic patients before and after absence seizures are characterized by a "slowdown" in transitions between microstates. Microstates might be used as an index to evaluate the temporal and spatial recovery process of absence seizures in AE.
Topics: Brain; Brain Mapping; Electroencephalography; Epilepsy, Absence; Humans; Seizures
PubMed: 33799135
DOI: 10.1016/j.seizure.2021.03.020 -
Current Neurology and Neuroscience... Jun 2017This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types. (Review)
Review
PURPOSE OF REVIEW
This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types.
RECENT FINDINGS
The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.
Topics: Consciousness; Dominance, Cerebral; Humans; Seizures; Societies, Medical
PubMed: 28425015
DOI: 10.1007/s11910-017-0758-6 -
Proceedings of the National Academy of... Mar 2022A growing number of gain-of-function (GOF) BK channelopathies have been identified in patients with epilepsy and movement disorders. Nevertheless, the underlying...
A growing number of gain-of-function (GOF) BK channelopathies have been identified in patients with epilepsy and movement disorders. Nevertheless, the underlying pathophysiology and corresponding therapeutics remain obscure. Here, we utilized a knock-in mouse model carrying human BK-D434G channelopathy to investigate the neuronal mechanism of BK GOF in the pathogenesis of epilepsy and dyskinesia. The BK-D434G mice manifest the clinical features of absence epilepsy and exhibit severe motor deficits and dyskinesia-like behaviors. The cortical pyramidal neurons and cerebellar Purkinje cells from the BK-D434G mice show hyperexcitability, which likely contributes to the pathogenesis of absence seizures and paroxysmal dyskinesia. A BK channel blocker, paxilline, potently suppresses BK-D434G–induced hyperexcitability and effectively mitigates absence seizures and locomotor deficits in mice. Our study thus uncovered a neuronal mechanism of BK GOF in absence epilepsy and dyskinesia. Our findings also suggest that BK inhibition is a promising therapeutic strategy for mitigating BK GOF-induced neurological disorders.
Topics: Animals; Channelopathies; Dyskinesias; Epilepsy, Absence; Humans; Large-Conductance Calcium-Activated Potassium Channels; Mice; Neurons; Seizures
PubMed: 35286197
DOI: 10.1073/pnas.2200140119 -
Neurophysiologie Clinique = Clinical... Aug 2022To analyze the ictal and interictal electroencephalographic (EEG) features in newly diagnosed childhood absence epilepsy (CAE) and determine the association between...
OBJECTIVE
To analyze the ictal and interictal electroencephalographic (EEG) features in newly diagnosed childhood absence epilepsy (CAE) and determine the association between seizure onset topography, interictal focal spike-wave discharges (FSWDs) and accompanying clinical features of absence seizures.
METHODS
The authors searched the EEG database for a definite diagnosis of CAE according to ILAE 2017 criteria. Video-EEGs of untreated pediatric patients during sleep and wakefulness were evaluated retrospectively.
RESULTS
The study included 47 patients (25 males, 22 females). Interictal FSWDs were observed in 49% of patients with CAE during wakefulness and in 85.1% during sleep (p = 0.001). Interictal FSWDs were most frequently observed in the frontal regions (awake: 34%; asleep: 74.5%), followed by the posterior temporoparietooccipital region (awake: 21.2%; asleep: 36.1%), and the centrotemporal region (awake: 6.4%; asleep: 8.5%). Eleven patients (23.4%) had polyspikes during sleep. Both bilateral symmetric and asymmetric seizure onset were noted in 32%, whereas focal seizure onset was observed in 14.9% of the patients. Absence seizures with and without motor components were seen in 72.3% and 61.7% of patients, respectively, and in 33% of patients both occurred. There were no associations between the existence of interictal FSWDs, focal/asymmetric seizure onset, and absence seizures with and/or without motor components.
CONCLUSION
Asymmetric and/or focal seizure onset, interictal FSWDs, and absence seizures with motor components are commonly observed in drug-naive CAE. This study found no association between seizure onset topography, interictal FSWDs, and semiological features of absence seizures.
Topics: Child; Electroencephalography; Epilepsy, Absence; Female; Humans; Male; Retrospective Studies; Seizures; Sleep
PubMed: 35953417
DOI: 10.1016/j.neucli.2022.07.003