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Brain : a Journal of Neurology Oct 2023While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using...
While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using evoked preclinical seizure models have shown that pharmacological activation or excitatory optogenetic stimulation of the deep and intermediate layers of the superior colliculus (DLSC) display multi-potent anti-seizure effects. Here we monitored and modulated DLSC activity to suppress spontaneous seizures in the WAG/Rij genetic model of absence epilepsy. Female and male WAG/Rij adult rats were employed as study subjects. For electrophysiology studies, we recorded single unit activity from microwire arrays placed within the DLSC. For optogenetic experiments, animals were injected with virus coding for channelrhodopsin-2 or a control vector, and we compared the efficacy of continuous neuromodulation to that of closed-loop neuromodulation paradigms. For each, we compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). For closed-loop stimulation, we detected seizures in real time based on the EEG power within the characteristic frequency band of spike-and-wave discharges (SWDs). We quantified the number and duration of each SWD during each 2 h-observation period. Following completion of the experiment, virus expression and fibre-optic placement was confirmed. We found that single-unit activity within the DLSC decreased seconds prior to SWD onset and increased during and after seizures. Nearly 40% of neurons displayed suppression of firing in response to the start of SWDs. Continuous optogenetic stimulation of the DLSC (at each of the three frequencies) resulted in a significant reduction of SWDs in males and was without effect in females. In contrast, closed-loop neuromodulation was effective in both females and males at all three frequencies. These data demonstrate that activity within the DLSC is suppressed prior to SWD onset, increases at SWD onset, and that excitatory optogenetic stimulation of the DLSC exerts anti-seizure effects against absence seizures. The striking difference between open- and closed-loop neuromodulation approaches underscores the importance of the stimulation paradigm in determining therapeutic effects.
Topics: Rats; Male; Humans; Animals; Female; Epilepsy, Absence; Superior Colliculi; Optogenetics; Seizures; Electroencephalography; Disease Models, Animal
PubMed: 37192344
DOI: 10.1093/brain/awad166 -
Emergency Medicine Clinics of North... May 2022New toxins are constantly emerging within society. We review common toxins that cause seizure, their mechanisms, associated toxidromes, and treatments. Stimulants,... (Review)
Review
New toxins are constantly emerging within society. We review common toxins that cause seizure, their mechanisms, associated toxidromes, and treatments. Stimulants, cholinergic agents, gamma-aminobutyric acid (GABA) antagonists, glutamate agonists, histamine and adenosine antagonists, and withdrawal states are highlighted. Understanding current mechanisms for common toxin-induced seizures can promote understanding of future toxins and predicting if seizure may occur as a result of toxicity.
Topics: Humans; Seizures; gamma-Aminobutyric Acid
PubMed: 35461631
DOI: 10.1016/j.emc.2022.01.010 -
Journal of Neurology, Neurosurgery, and... Sep 2019Almost 10% of people will experience at least one seizure over a lifetime. Although common, first seizures are serious events and warrant careful assessment and... (Review)
Review
Almost 10% of people will experience at least one seizure over a lifetime. Although common, first seizures are serious events and warrant careful assessment and management. First seizures may be provoked by acute or remote symptomatic factors including life-threatening metabolic derangements, drug toxicity or structural brain lesions. An unprovoked first seizure may herald the onset of epilepsy and may be accompanied by medical and psychiatric illnesses. Accidents, injuries and death associated with first seizures are likely under-reported. The cognitive and emotional impact of first seizures is often neglected. Evaluation of a patient presenting with a first seizure requires careful history-taking and early specialist assessment, however optimal management strategies have not been extensively investigated. Further, advances in technology and the role of eHealth interventions such as telemedicine may be of value in the care of patients who have experienced a first seizure. This article reviews the impact and implications of first seizures beyond the scope provided in current guidelines which tend to focus on assessment and management. It examines the effect of first seizures on the well-being of patients; assesses morbidity and premature mortality in first seizures and discusses current and future directions to optimise safety and health of people with first seizures, with a focus on adult patients. Recognition of these issues is essential to provide adequate care for people with first seizures.
Topics: Adult; Anticonvulsants; Humans; Medical History Taking; Risk Factors; Seizures
PubMed: 30948624
DOI: 10.1136/jnnp-2018-320215 -
The Journal of Pediatrics Mar 2022To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.
OBJECTIVE
To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.
STUDY DESIGN
The Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease.
RESULTS
We evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P < .001) and experience their first seizure later than those without cardiopulmonary disease (174 vs 21 hours of age, P < .001), but they had similar seizure exposure (many-recurrent electrographic seizures 39% vs 43%, P = .27). Phenobarbital was the primary initial antiseizure medication for both groups (90%), and both groups had similarly high rates of incomplete response to initial antiseizure medication administration (66% vs 68%, P = .75). Neonates with cardiopulmonary disease were discharged from the hospital later (hazard ratio 0.34, 95% CI 0.25-0.45, P < .001), although rates of in-hospital mortality were similar between the groups (hazard ratio 1.13, 95% CI 0.66-1.94, P = .64).
CONCLUSION
Neonates with and without cardiopulmonary disease had a similarly high seizure exposure, but neonates with cardiopulmonary disease were more likely to experience EEG-only seizures and had seizure onset later in the clinical course. Phenobarbital was the most common seizure treatment, but seizures were often refractory to initial antiseizure medication. These data support guidelines recommending continuous EEG in neonates with cardiopulmonary disease and indicate a need for optimized therapeutic strategies.
Topics: Anticonvulsants; Electroencephalography; Epilepsy; Humans; Infant, Newborn; Monitoring, Physiologic; Phenobarbital; Seizures
PubMed: 34728234
DOI: 10.1016/j.jpeds.2021.10.058 -
Journal of the American Psychiatric... 2023Psychogenic nonepileptic seizures (PNES) pose a heavy burden on patients' lives and the health care system. The symptoms of PNES are often debilitating and cause high... (Review)
Review
BACKGROUND
Psychogenic nonepileptic seizures (PNES) pose a heavy burden on patients' lives and the health care system. The symptoms of PNES are often debilitating and cause high rates of disability and poor quality of life. Many treatment options are available, but there is no clear consensus on best practices.
AIM
To critique and synthesize the current literature on nonpharmacologic interventions and effects on seizure frequency in patients with PNES.
METHODS
An integrative review guided by the Whittemore and Knafl approach.
RESULTS
The review included 24 studies published from 2010 to 2020. Interventions for PNES included individualized psychotherapies, group therapies, multimodal psychotherapies, self-help therapies, and complementary and alternative medicine therapies. Individual psychotherapies such as cognitive behavioral therapy and psychoeducation were the most used treatment modalities. The most effective treatments for seizure frequency reduction were those that included multiple psychotherapy sessions with a health care provider and covered multiple domains (e.g., understanding of diagnosis, identifying triggers, and developing effective coping strategies).
CONCLUSIONS
Seizure frequency can be reduced in patients with PNES with multiple nonpharmacologic interventions. However, seizure frequency is not considered a comprehensive outcome measure and provides little insight into other important life domains. Further research is needed on nonpharmacologic interventions for PNES and effects on other areas of life such as sleep, employment status, global functioning, and self-efficacy.
Topics: Humans; Quality of Life; Psychogenic Nonepileptic Seizures; Seizures; Psychotherapy; Cognitive Behavioral Therapy
PubMed: 35801259
DOI: 10.1177/10783903221107637 -
Epilepsy & Behavior : E&B Nov 2023The continuously expanding research and development of wearable devices for automated seizure detection in epilepsy uses mostly non-invasive technology. Real-time... (Review)
Review
INTRODUCTION AND PURPOSE
The continuously expanding research and development of wearable devices for automated seizure detection in epilepsy uses mostly non-invasive technology. Real-time alarms, triggered by seizure detection devices, are needed for safety and prevention to decrease seizure-related morbidity and mortality, as well as objective quantification of seizure frequency and severity. Our review strives to provide a state-of-the-art on automated seizure detection using non-invasive wearable devices in an ambulatory (home) environment and to highlight the prospects for future research.
METHODS
A joint working group of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) recently published a clinical practice guideline on automated seizure detection using wearable devices. We updated the systematic literature search for the period since the last search by the joint working group. We selected studies qualifying minimally as phase-2 clinical validation trials, in accordance with standards for testing and validation of seizure detection devices.
RESULTS
High-level evidence (phases 3 and 4) is available only for the detection of tonic-clonic seizures and major motor seizures when using wearable devices based on accelerometry, surface electromyography (EMG), or a multimodal device combining accelerometry and heart rate. The reported sensitivity of these devices is 79.4-96%, with a false alarm rate of 0.20-1.92 per 24 hours (0-0.03 per night). A single phase-3 study validated the detection of absence seizures using a single-channel wearable EEG device. Two phase-4 studies showed overall user satisfaction with wearable seizure detection devices, which helped decrease injuries related to tonic-clonic seizures. Overall satisfaction, perceived sensitivity, and improvement in quality-of-life were significantly higher for validated devices.
CONCLUSIONS
Among the vast number of studies published on seizure detection devices, most are strongly affected by potential bias, providing a too-optimistic perspective. By applying the standards for clinical validation studies, potential bias can be reduced, and the quality of a continuously growing number of studies in this field can be assessed and compared. The ILAE-IFCN clinical practice guideline on automated seizure detection using wearable devices recommends using clinically validated wearable devices for automated detection of tonic-clonic seizures when significant safety concerns exist. The studies published after the guideline was issued only provide incremental knowledge and would not change the current recommendations.
Topics: Humans; Seizures; Epilepsy, Tonic-Clonic; Epilepsy, Absence; Electroencephalography; Wearable Electronic Devices
PubMed: 37857030
DOI: 10.1016/j.yebeh.2023.109486 -
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 -
The Journal of Pediatrics Apr 2022
Topics: Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Seizures
PubMed: 34896429
DOI: 10.1016/j.jpeds.2021.12.004 -
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