Prolonged Seizures Research Articles

Impacted spike frequency adaptation associated with reduction of KCNQ2/3 exacerbates seizure activity in temporal lobe epilepsy.

Numerous epilepsy-related genes have been identified in recent decades by unbiased genome-wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation. In this study, we reveal the significant role of KCNQ2 and KCNQ3, two M-type potassium channel genes, in the onset of seizures in TLE. Our investigation began with a quantitative analysis of two publicly available TLE patient databases to establish a correlation between seizure onset and the downregulated expression of KCNQ2/3. We then replicated these pathological changes in a pilocarpine seizure mouse model and observed a decrease in spike frequency adaptation due to the affected M-currents in dentate gyrus granule neurons. In addition, we performed a small-scale simulation of the dentate gyrus network and confirmed that the impaired spike frequency adaptation of granule cells facilitated epileptiform activity throughout the network. This, in turn, resulted in prolonged seizure duration and reduced interictal intervals. Our findings shed light on an underlying mechanism contributing to ictogenesis in the TLE hippocampus and suggest a promising target for the development of antiepileptic drugs.

Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1β signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1β converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.

Abstract 17489: Bupropion Poisoning: Extracorporeal Membrane Oxygenation as a Rescue Strategy

Introduction: Bupropion is a commonly prescribed antidepressant. Although generally well-tolerated, bupropion overdose can lead to severe cardiovascular and neurological toxicity. We present a case of cardiogenic shock and status epilepticus as a result of bupropion intoxication. Case Presentation: A 29-year-old female with history of depression and borderline personality disorder presented to the emergency department unresponsive after ingesting large quantities of bupropion, alprazolam and lisdexamfetamine. Vital signs were unremarkable and physical exam revealed pupil asymmetry. CT head was unremarkable. Urine toxicology was positive for amphetamines and benzodiazepines, with a blood alcohol level of 104. QTc was 522. Patient received versed for status epilepticus and was placed on mechanical ventilation. She developed sustained ventricular tachycardia and hypotension, unresponsive to bicarbonate and amiodarone. The patient was placed on venoarterial extracorporeal membrane oxygenation (VA ECMO) to provide hemodynamic support while eliminating bupropion from circulation. Following repeated episodes of VT, the patient was successfully cardioverted and started on amiodarone. TTE demonstrated left ventricular ejection fraction (LVEF) of <30%. Notably, lipid emulsion therapy was not administered as patient stabilized with ECMO support. After 48 hours of electrical stability, she was weaned off ECMO and inotropes and transitioned to guideline-directed medical therapy. Repeat TTE demonstrated LVEF of 60% on day 12. Mental status improved and patient was admitted to psychiatry with outpatient cardiology follow-up. Discussion: Bupropion overdose can cause prolonged QTc, ventricular arrhythmias, and seizures. Cardiotoxicity results from inhibition of gap junction ion channels, compromising conduction and contractility. Various approaches, including ECMO and lipid emulsion therapy, have been effectively employed in such cases. This case demonstrates that ECMO can serve as a hemodynamic bridge during the elimination of bupropion while augmenting its clearance via increased flow, underscoring the benefits of mechanical circulatory support in cases of intoxication affecting cardiac contractility and conduction.

Initial Management of Status Epilepticus

Status epilepticus(SE)is defined as a prolonged seizure and is a common neurological emergency with high morbidity and mortality rates. As uncontrolled SE causes irreversible neurological damage, prompt diagnosis and treatment are required. If anti-seizure medications and benzodiazepines, which are initial treatments for SE, are not effective and SE deteriorates to refractory, anesthetic drugs are needed to suppress seizure activity under electroencephalogram(EEG)monitoring. Continuous EEG monitoring is useful not only for evaluating the control of SE but also for diagnosing non-convulsive SE(NCSE)and psychogenic non-epileptic seizures. New-onset refractory status epilepticus is defined as refractory SE in a patient without active epilepsy and without a clear acute or active structural, toxic, or metabolic cause. Because autoimmune encephalitis is the most frequently identified cause, immunotherapy can be attempted in addition to antiepileptic treatment within 2 weeks. Although NCSE is the major cause of unconsciousness, diagnosis is difficult because of uncertain clinical symptoms. Continuous EEG monitoring over 24 h is crucial for diagnosis, although arterial spin labeling-magnetic resonance imaging is alternatively useful. Finally, the building of a multidisciplinary cooperation system is required for prompt diagnosis and intensive treatment for controlling SE.

Integrated bioinformatics and validation to construct lncRNA-miRNA-mRNA ceRNA network in status epilepticus

BackgroundStatus epilepticus (SE) is a neurologic emergency with characteristic of prolonged seizure activity. However, the investigation of lncRNA based competing endogenous RNAs (ceRNAs) network in SE still requires further elucidation. This study aims to construct the ceRNA network and uncover the related mechanism in SE. MethodsThe C57BL/6 mice pilocarpine-induced (SE) model was established (i.p. injection, 300 mg/kg) (n = 3). RNA-Sequencing was carried out and identified the differential expressed genes (DEGs). GO annotations, KEGG, and GSEA analysis were performed to study the underlying mechanism and pathways of the DEGs. Further, the protein-protein interaction (PPI) network and ceRNA network were visualized by Cytoscape software. The expression level of differential expressed genes involved in the ceRNA network was detected by qRT-PCR. ResultsA total of 345 DE-mRNAs, 84 DE-lncRNAs, and 5 DE-miRNAs were screened out. Subsequently, the functional analysis suggested that angiogenesis, inflammation, and neuron related biological processes were enriched in SE. The constructed ceRNA network-1 contained 7 up-regulated DE-mRNAs (Arid5a, Adm, Insig1, Midn, Btaf1, Per1, Slc25a25), 1 down-regulated DE-miRNA (mmu-miR-6413), and 1 up-regulated DE-lncRNA (Zmiz1os1). The ceRNA network-2 contained 2 down-regulated DE-mRNAs (Rab27a and Lrp2), 1 up-regulated DE-miRNAs (mmu-miR-139–5p), and 1 down-regulated DE-lncRNA (Gm15883). ConclusionFor the first time this study present the expression profile and potential function of lncRNAs in C57BL/6 mice with SE. These results provided novel insights into the discovery of genetic biomarkers for SE.

The real-world effectiveness of intravenous brivaracetam as a second-line treatment in status epilepticus

PurposeStatus epilepticus (SE) is defined by abnormally prolonged seizures that may lead to brain damage and death. Our aim was to evaluate the efficacy and tolerability (effectiveness) of intravenous brivaracetam (BRV) as a second-line treatment. Methods: Twenty-one patients (median age 68 years ± 17.28) were prospectively recruited between June 2019 and December 2022. Patients were treated with BRV (50–200 mg) as a second-line add-on therapy for SE. We evaluated the response of SE to the administration of BRV in terms of SE termination and recurrence of epileptic seizures at 6, 12, and 24 h, also monitoring safety. The first-line therapy was represented by intravenous benzodiazepines (mainly diazepam). Results: Almost a quarter of patients had generalized seizures, whereas the vast majority (76.2%) presented focal seizures. In 52.4% of patients, the underlying cause was cerebrovascular. Fourteen (66.7%) patients displayed a good early response in the subsequent 6 h. At 12 and 24 h, 8 (38%) and 11 (52.4%) patients, respectively, did not present seizures. Conclusion: The present study highlights the potential of BRV when used as an early add-on therapy in SE, further confirming its good safety profile.

A - 94 A Case of New Onset Refractory Status Epilepticus (NORSE) Associated with COVID-19.

New Onset Refractory Status Epilepticus (NORSE) is a rare condition of prolonged medication-refractory seizures potentially due to elevated inflammatory molecules in the brain. NORSE can be triggered by a viral infection and is a documented neurologic consequence of COVID-19. A 74-year-old, left-handed, Hispanic male was in his usual state of health until experiencing 1-2weeks of speech decline, which culminated in an episode of altered mental status (disorientation and mumbling speech). He presented to the Emergency Department with drowsiness and complaints of a "funny feeling" on the left side of his head. Upon arrival, he was found to be COVID-19 positive and hyperglycemic with normal CT, MRI, lumbar puncture, and bloodwork. An EEG showed "focal temporal activity" and he was diagnosed with non-convulsant status epilepticus. Hospitalization and medical sedation lasted 2months followed by 8months of inpatient rehabilitation. The patient was discharged shortly before presenting for neuropsychological evaluation. Neuropsychological evaluation showed weaknesses in learning and free recall, visuospatial skills (due to disorganization and poor attention to details), processing speed, and executive functioning. The patient reported elevated anxiety symptoms. Collateral report indicated severe declines in executive organizational abilities, as well as mild memory and divided attention declines. Results suggest frontal cortical and subcortical impairments affecting multiple areas of cognition and functional decline consistent with a diagnosis of major neurocognitive disorder. Similar to the literature, status epilepticus was attributed to inflammatory meningoencephalitis triggered by the prior COVID-19 infection. Interdisciplinary care was an integral factor in this case.

Factors predicting seizure outcome after surgical excision of meningioma: SOLID-C guideline for prophylactic AED

BackgroundSeizures are commonly seen among meningioma patients and may cause impaired quality of life. These patients can be effectively treated with surgery. Still, many patients have persistent seizure episodes after surgery. The factors which are associated with worsening of seizure episodes remain critical in improving the quality of life for such patients. In this study, we aim to analyze the clinical and histopathological factors to predict the post excision seizure-outcome in meningioma and need of antiepileptic prophylaxis for these patients. MethodsAdult patients who underwent primary resection of meningioma at our institute between 2007 and 2020 were included in the study. Eligibility criteria were as follows: (i) Surgery for newly-diagnosed biopsy proven meningioma, (ii) Presence of pre-operative seizure (iii) A follow-up period ≥ 12 months. ResultsOf the 1145 patients in this series, 333 patients were recruited in study. The major determinants of prophylactic anti-epileptic were tumour size (S), Oedema (O), location (L), inclusion body (I), antiepileptic drugs (D) and surgical complication (C). The factors independently associated with poor seizure control after surgical resection were presence of brain parenchyma invasion (p < 0.001), pre-operative use of > 2 antiepileptics (p = 0.016) and presence of intranuclear inclusion bodies (p = 0.001). ConclusionsThe identification and consideration of factors associated with prolonged seizure control after surgery may help us to guide treatment strategies aimed at improving the quality of life for patients with meningiomas. Authors have proposed a SOLID-C guideline to avoid the blanket approach of prophylactic AED in patients undergoing for meningioma resection.

Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective.

Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Observational study based on online surveys of owners of dogs with emergency seizure disorders. The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.

Individualized seizure cluster prediction using machine learning and chronic ambulatory intracranial EEG.

Epilepsy patients often experience acute repetitive seizures, known as seizure clusters, which can progress to prolonged seizures or status epilepticus if left untreated. Predicting the onset of seizure clusters is crucial to enable patients to receive preventative treatments. Additionally, studying the patterns of seizure clusters can help predict the seizure type (isolated or cluster) after observing a just occurred seizure. This paper presents machine learning models that use bivariate intracranial EEG (iEEG) features to predict seizure clustering. Specifically, we utilized relative entropy (REN) as a bivariate feature to capture potential differences in brain region interactions underlying isolated and cluster seizures. We analyzed a large ambulatory iEEG dataset collected from 15 patients and spanned up to 2 years of recordings for each patient, consisting of 3341 cluster seizures (from 427 clusters) and 369 isolated seizures. The dataset's substantial number of seizures per patient enabled individualized analyses and predictions. We observed that REN was significantly different between isolated and cluster seizures in majority of the patients. Machine learning models based on REN (i) predicted whether a seizure will occur soon after a given seizure with up to 69.5% Area under the ROC Curve (AUC), and (ii) predicted if a seizure is the first one in a cluster with up to 55.3% AUC, outperforming baseline techniques. Overall, our findings could be beneficial in addressing the clinical burden associated with seizure clusters, enabling patients to receive timely treatments and improving their quality of life.

Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

Sex differences are common in human epilepsy. Although men are more susceptible to seizure than women, the mechanisms underlying sex-specific vulnerabilities to seizure are unclear. The organophosphate (OP) diisopropylfluorophosphate (DFP) is known to cause neurotoxicity and status epilepticus (SE), a serious neurologic condition that causes prolonged seizures and brain damage. Current therapies for OP poisoning and SE do not consider neuronal variations between male and female brains. Therefore, we investigated sex-dependent differences in electrographic seizure activity and neuronal injury using the DFP model of refractory SE in rats. Electroencephalogram recordings were used to monitor DFP-induced SE, and the extent of brain injury was determined using fluoro-jade-B staining to detect cellular necrosis. After DFP exposure, we observed striking sex-dependent differences in SE and seizure activity patterns as well as protective responses to midazolam treatment. Following acute DFP exposure, male animals displayed more severe SE with intense epileptiform spiking and greater mortality than females. In contrast, we observed significantly more injured cells and cellular necrosis in the hippocampus and other brain regions in females than in males. We also observed extensive neuronal injury in the somatosensory cortex of males. The anticonvulsant effect of midazolam against SE was limited in this model and found to be similar in males and females. However, unlike males, females exhibited substantially more protection against neuronal damage after midazolam treatment. Overall, these results demonstrate significant sex-dependent differences in DFP-induced refractory SE and neuronal damage patterns, suggesting that it may be possible to develop sex-specific neuroprotective strategies for OP intoxication and refractory SE. SIGNIFICANCE STATEMENT: Sex-dependent differences in neurotoxicity and status epilepticus (SE) are key biological variables after organophosphate (OP) exposure. Here, we investigated sex-dependent differences in SE and brain injury after acute diisopropylfluorophosphate exposure. Male rats had more severe SE and less survival than females, while females had more neuronal damage. Females had more neuroprotection to midazolam than males, while both sexes had similar but partial anticonvulsant effects. These findings suggest that a sex-specific therapeutic approach may prevent neurological complications of OP-induced SE.

Dissociative seizures in the emergency room: room for improvement

BackgroundDissociative seizures, also known as functional or psychogenic non-epileptic seizures, account for 11%–27% of all emergency seizure presentations. Misdiagnosis as epileptic seizures is common and leads to ineffective and potentially...

Development and validation of a peripheral cell ratio and lactate score for differentiating status epilepticus from prolonged psychogenic nonepileptic seizures.

Differentiating status epilepticus (SE) from prolonged psychogenic nonepileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Retrospective two-center study investigating the sensitivity and specificity of acute (≤12 h of event offset) peripheral cell counts, cell ratios (neutrophil-lymphocyte ratio, neutrophil-monocyte ratio, monocyte-lymphocyte ratio, platelet-lymphocyte ratio, systemic immune-inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalized additive models to generate biomarker vs time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII, or SIRI with lactate levels were developed and validated in separate cohorts. For the development cohort, 1262 seizure-like events were reviewed and 79 SE and 44 pPNES events were included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events were included. Individually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with the neutrophil count, SIRI, and SII performing best with sensitivities of 0.65-0.84, specificities of 0.64-0.89, and ROC AUCs of 0.78-0.79. Lactate levels peaked at 60 min, while cell counts and ratios peaked after 240 min. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75 and 0.79, specificities between 0.93 and 1.00, and ROC AUCs of 0.89-0.91. Lactate levels peak early post-SE, whereas cell counts and ratios do so later. The differing post-event time profiles of lactate levels vs neutrophil count, SIRI, and SII allow incorporation into three separate scores which can assist in differentiating SE from pPNES.

Pharmacological inhibition of ictal and interictal epileptiform discharges

Background: Epilepsy is a brain disorder characterized by an enduring predisposition to generate epileptic seizures. Seizures are a transient occurrence of signs and/or symptoms due to abnormal excessive and synchronous neuronal activity in the brain. Electroencephalogram (EEG), a non-invasive instrumental test, has an important role in the diagnosis of epilepsy, as well as in monitoring the results and long-term treatment because it can detect interictal and ictal discharges that are crucial for confirmation and classification of seizures. Antiepileptic drugs are the first treatment option in patients with epilepsy, although the effectiveness of such drugs is limited only to symptom control and requires a regular intaking by the patient. These drugs exploit the cell membrane channels, modifying their permeability, allowing either an increase in the inhibitory neurotransmission or the reduction in the excitatory one, by hyperpolarizing neurons and avoiding the recurrence of the epileptic seizures without reversing or stopping the underlying mechanism of epileptogenesis. Materials and Methods: The internship took place in the Neurophysiopathology department of the Antonio, Biagio and Cesare Arrigo’s hospital in Alessandria, from October 2022 to March 2023. During this period, it was possible to attend the emergency treatment of prolonged and recurrent epileptic seizures during EEGrafic recording and the consequential amendments of the ictal discharges induced by the administration of antiepileptic drugs. Follow up EEG was also performed to investigate the modifications of interictal activity after a period of treatment with antiepileptic drugs. The patient who has been analyzed in this paper, underwent EEG recordings obtained by using bridge electrodes placed on the scalp according to the international 10-20 system. Objectives: The aim of this study is to analyze the mechanisms of action of the main antiepileptic drugs, in relation to the physiological cellular mechanisms regulating the neuronal excitability and their effect on the ictal and interictal epileptiform discharges in the EEG recordings.

New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development. These can be broadly divided into three groups. The first group consists of positive allosteric modulators of GABAA receptors and includes Staccato® alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101. A second group comprises two drugs already marketed for non-neurological indications, which could be repurposed as treatments for seizure disorders. These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents and restoring the function of GABAergic interneurons, currently tested in a trial in patients with Dravet syndrome, and an adenoviral vector-based gene therapy (ETX-101) scheduled for investigation in Dravet syndrome. Another agent, a subcutaneously administered neuroactive peptide (NRP2945) that reportedly upregulates the expression of GABAA receptor α and β subunits is being investigated, with Lennox-Gastaut syndrome and other epilepsies as proposed indications. The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.

Event-Based Epileptic Seizure Detection with Stacked Convolutional Restricted Boltzmann Machine

Research indicates that around 1% of the global population experiences epileptic seizures, described as an undue neuronal discharge in the brain, which can significantly impact the quality of life for those affected. Children who experience frequent or prolonged seizures may experience lasting cognitive damage and psychological difficulties, and sudden seizures can pose a serious risk of injury or even death. Therefore, developing an accurate machine learning model to predict seizures is crucial. This study introduces an Event-based Stacked Convolutional Restricted Boltzmann Machine architecture that can detect ictal periods in EEG signals. The model was trained and evaluated on a publicly available dataset of EEG recordings from 24 pediatric patients, achieving a high prediction accuracy of 94.2%, with a mean prediction time of 19.62 min. The model's mean sensitivity and specificity rates were also comparable to those of state-of-the-art predictive models on the CHB-MIT dataset.

A Retrospective Matched Comparison Study of Prolonged Seizures in ECT.

This study assessed the incidence of and risk factors for prolonged seizures (>180 sec) in electroconvulsive therapy (ECT). In 611 adult patients undergoing 6697 ECT treatments administered over a 2.5-year study period, 29 individuals experienced 42 prolonged seizures. A comparison sample (n = 29) was matched on sex, age, and treatment, and compared on psychiatric and medical diagnoses, as well as current medications. To examine the association between the characteristics and prolonged seizure, conditional logistic regression models or exact McNemar tests were conducted. Prolonged seizures occurred on average in 1 of every 167 treatments. No specific psychiatric disorders or medical conditions were associated with the prolonged seizure group. Antipsychotic drugs were used in a higher proportion of the comparison group than in the prolonged seizure group, suggesting a protective effect. Atropine was used in a lower proportion of the long seizure group than in the comparison group. No untoward sequelae occurred, and no progression to status epilepticus was observed. Prolonged seizures appear to be an uncommon complication of ECT in adults. The characteristics examined in this study suggest limited association of psychotropic medications with prolonged seizures. Treatment of prolonged seizures was straightforward. Prolonged seizures had no impact on the course of treatment. Further exploration of prolonged seizures would enhance the generalizability of the findings from this single site study.

Electroconvulsive therapy and seizure: a double-edged sword?

Electroconvulsive therapy (ECT) is a widely used therapeutic option of drug-refractory psychiatric disorders. ECT treats psychiatric symptoms by inducing brief controlled seizures through electrical stimulation, but ECT does not generally cause prolonged seizures or epilepsy. However, several studies have reported cases of prolonged seizures after ECT. This review aimed to determine the mechanism of epileptogenesis with neurobiological changes after ECT. Contrary to epileptogenesis by ECT, several cases have reported that ECT was successfully applied for treatment of refractory status epilepticus. In addition, ECT might be applied to hyperkinetic movement and psychiatric symptoms of encephalitis. We also investigated the anticonvulsant mechanism of ECT and how it controls encephalitis symptoms.

P300 event-related potentials in people with epilepsy: clinico-neurophysiologic study

BackgroundThere is increasing evidence that prolonged or recurrent seizures can cause or exacerbate cognitive impairment (CI) in memory, attention, orientation, and visuospatial and abstraction disabilities, all of which can jeopardize educational progress and achievement throughout life. The objectives of our study are to assess the cognitive functions in people with epilepsy (PwE) using P300 event-related potentials (ERPs), and correlate each P300 components with six explanatory variables (epilepsy type, seizure type, NHS3 score- seizure severity, disease duration, age at first seizure, and the number of anticonvulsant medications).MethodsOne hundred and two PwE [52 with focal epilepsy and 50 with generalized epilepsy, as classified by the International League Against Epilepsy in 2017]. They underwent electroencephalography (EEG) and P300. The Montreal Cognitive Assessment (MoCA) scale was used to assess baseline cognitive functions.ResultsEpileptic patients showed significant latency prolongation and amplitude reduction of P300 as compared to non-epileptic population. Longer P300 latency and lower amplitude were seen in patients with abnormal EEG records. P300 latency was longer in patients using poly-therapy. P300 components correlated well with age at presentation and disease duration but not with NHS3. According to epilepsy type, 50.98% of PwE had focal epilepsy and 49.02% had generalized epilepsy, 85.29% of them had abnormal EEG recording. Considering seizure type, 47.06% had a generalized tonic–clonic seizure, 38.24% had a focal to bilateral tonic–clonic seizure, 20.59% had a myoclonic seizure, 12.75% had a focal with impaired awareness seizure, 3.92% had a focal aware seizure, and 2.94% had an absence seizure. Seventy-seven PwE had one type of seizure, while 25 had more than one type of seizure. The NHS3 score was higher in those with a single seizure type than in those with multiple seizure types.ConclusionAll seizure types had an abnormal P300 component, indicating cognitive function deficits. P300 may be a promising objective method for assessing cognitive function in PwE. The number of antiepileptic drugs used, the presence of EEG abnormalities, the age at presentation, and the duration of the disease are the factors that best correlate with cognitive impairment (CI).

Sublingual lorazepam as rescue therapy for seizure emergencies in adults

ObjectiveLimited acute home treatments are available for patients with prolonged (>5 minutes) or repetitive (≥2 in 24 hours) seizures. While this early seizure treatment may reduce the need for emergency care, intermittent intranasal benzodiazepine formulations are expensive and rectal diazepam administration is often socially unacceptable. We determined whether caregivers could use sublingual lorazepam oral concentrate solution effectively as acute treatment for adults with prolonged and repetitive seizures. MethodsPatients prescribed sublingual lorazepam solution at the Johns Hopkins Epilepsy Center for acute seizure treatment during a 5-year period (2012–2017) were screened. We determined clinical history of seizure patterns and number of antiseizure medications (ASMs) through patient and caregiver surveys, and we verified this history in patients’ medical records and charts. During a 2-year span (2017–2018), patients and caregivers were surveyed on responses to their most recent use of sublingual lorazepam solution, including seizure cessation (prolonged seizure stopping <5 minutes or ≤1 repetitive seizure), presence of sedation and adverse events within 24 hours of administration, and whether refrigeration limited use. ResultsIn total, 52 patients used sublingual lorazepam for treatment of acute seizures during the study period (median dose 1 mg, range 0.5 to 2 mg). Of them, 48 patients participated in treatment survey interviews. Family caregivers usually administered lorazepam (88%); 3 self-administered. Patients were surveyed on responses to their most recent use of sublingual lorazepam treatment: 66% (23/35) of patients with repetitive seizures reported no further seizure activity after administering treatment; 70% (7/10) with prolonged seizures reported seizure activity ceased within 5 minutes of treatment. Three patients treated auras and had no seizures. There were no serious adverse events during most recent use: 31% of patients developed moderate/severe sedation. Of note, 98% refrigerated lorazepam, often with coolers; 44%, however, said this limited treatment access. There was high treatment satisfaction; 79% reported that having the emergency treatment available made them feel safer. SignificanceThis patient survey and retrospective chart review demonstrates that home treatment with sublingual lorazepam solution may be effective for interrupting prolonged and repetitive seizures. No patients had sedation complications with home doses of 0.5 to 2 mg, and patients report high satisfaction with the treatment.