Seizure Clusters Research Articles

Application Of Plan-Do-Study-Act Method In Seizure Rescue Medication Practices: A Single Pediatric Neurology Clinic Quality Improvement Study (P4-9.008)

<h3>Objective:</h3> To assess if seizure rescue medications are prescribed appropriately with adequate documentation in the medical records for convulsive seizures. <h3>Background:</h3> Administration of appropriate seizure rescue medication is crucial in management of prolonged seizure and seizure cluster to avoid progression to status epilepticus. <h3>Design/Methods:</h3> The study is a retrospective single outpatient clinic analysis of pediatric patients with convulsive seizures employing the ‘plan-do-study-act’ (PDSA) method for quality assessment. Two separate cohorts-PDSA1 and PDSA2 were compared at two separate time frames spanning three months each with educational session in between, with analysis of outcome and process measures. <h3>Results:</h3> 38 and 30 patients were enrolled in PDSA1 and PDSA2 cycles respectively. In PDSA1 cohort, 25 patients (65.8%) had appropriate rescue prescriptions. Out of the rest, 8 (21.2%) were not prescribed medications due to unclear reasons and 5(13%) were seizure free for more than 2 years. In PDSA2 cohort, the percentage of rescue medication prescribed improved to 73%. Clonazepam ODT was the most prescribed rescue medication in both cohorts. There was an increase in prescribing trend of Valtoco and Nayzilam noted in the PDSA2 cohort. Increase in intranasal rescue medication from 11% to 32% and decrease in rectal rescue medication from 21% to 9% were noted in PDSA2. The analysis of appropriate dosing of medications and proper documentation in PDSA2 cohort was high, 95% and 89% respectively. <h3>Conclusions:</h3> Our study showed improvement of seizure rescue medication prescription practices in PDSA2 compared to PDSA1 cycles. The role of educational session for fellows, attending physicians and patient family regarding the timing of rescue medication, appropriate options, and correct dosing after the PDSA1 cycle was significant. Effective strategy of implementing systematic and rigorous standards in PDSA cycles sequentially could improve the prescription rate to 100% for convulsive seizures and consequently result in reduction in number of ED visits for breakthrough seizures and status epilepticus admissions. <b>Disclosure:</b> Dr. Peringassery Sateesh has nothing to disclose. Dr. Mohammadpour Touserkani has nothing to disclose. Dr. Andriotis has nothing to disclose. Ms. Shafiq has nothing to disclose. Dr. Chari has nothing to disclose.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience

ObjectiveNearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. MethodsRetrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. Results97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 – 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 – 9.7). No severe treatment emergent adverse events were observed. SignificanceIn our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

カルバマゼピン投与によるミオクロニー発作増悪時にDoose症候群と診断しエトスクシミドが著効した3歳男児

A 3-year-old boy with a history of four febrile convulsions since the age of 1 year was admitted to the hospital after experiencing a cluster of tonic seizures. Treatment was started with valproic acid (VPA), which proved to be ineffective, so carbamazepine (CBZ) was administered instead. This was judged to be effective because the tonic seizures disappeared temporarily. The patient was discharged, but he then had a similar cluster of tonic seizures and was consequently readmitted. Zonisamide (ZNS) was administered, which resolved the tonic seizures. CBZ was discontinued because we thought it would exacerbate the myoclonic seizures he was experiencing. The myoclonic seizures disappeared, and the addition of ethosuximide (ESM) completely resolved his tonic seizures. In this patient, the onset of tonic seizures was characterized by clusters, but because myoclonic seizures were not prominent initially, we were unable to diagnose Doose syndrome early. However, ESM proved remarkably effective, and the patient has remained seizure free.

NAPB and developmental and epileptic encephalopathy: Description of the electroclinical profile associated with a novel pathogenic variant.

Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. DEE are genetically heterogeneous, and the proteins involved play roles in multiple pathways such as synaptic transmission, metabolism, neuronal development or maturation, transcriptional regulation, and intracellular trafficking. We performed whole exome sequencing on a consanguineous family with three children presenting an early onset (<6 months) with clusters of seizures characterized by oculomotor and vegetative manifestations, with an occipital origin. Before 1 year of age, interictal electroencephalographic recordings were well organized and neurodevelopment was unremarkable. Then, a severe regression occurred. We identified a novel homozygous protein-truncating variant in the NAPB (N-ethylmaleimide-sensitive fusion [NSF] attachment protein beta) gene that encodes the βSNAP protein, a key regulator of NSF-adenosine triphosphatase. This enzyme is essential for synaptic transmission by disassembling and recycling proteins of the SNARE complex. Here, we describe the electroclinical profile of each patient during the disease course. Our findings strengthen the association between biallelic variants in NAPB and DEE and refine the associated phenotype. We suggest including this gene in the targeted epilepsy gene panels used for routine diagnosis of unexplained epilepsy.

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Lawrence J. HirschLawrence J. HirschLawrence J. Hirsch, MD is Professor of Neurology, Chief of the Division of Epilepsy and EEG, and Co-Director of the Comprehensive Epilepsy Center, all at Yale University, USA. He has held leadership positions in the American Clinical Neurophysiology Society (ACNS), American Epilepsy Society, American Academy of Neurology, and the Epilepsy Foundation, and is lead author of the 2012 and 2021 ACNS guidelines on critical care EEG terminology. He is founder and former chair of the Critical Care EEG Monitoring Research Consortium, which now includes more than 50 centers, and co-chair of the medical advisory board of the NORSE Institute. He has been an active researcher throughout his career, having published more than 200 peer-reviewed manuscripts and more than 100 reviews, editorials or book chapters on topics including status epilepticus, all aspects of EEG including intracranial recordings and brain monitoring in the critically ill, brain stimulation, epilepsy surgery, seizure clusters, rescue medications, sudden death in epilepsy (SUDEP), and anti-seizure medication use. He has won multiple teaching awards and is co-author of the first-ever atlas on EEG in critical care, now in its 2nd edition. He continues to see patients in the inpatient and outpatient setting, direct fellowship programs, teach, mentor, and manage a large epilepsy division at a level IV Comprehensive Epilepsy Center. Michael F. WatersMichael F. WatersMichael F. Waters, MD, PhD, is a neurologist, director of both the Neurovascular Division and the Petznick Stroke Center, and a professor in the Department of Neurology at Barrow Neurological Institute, USA. He is board certified in neurology by the American Board of Psychiatry and Neurology with subspecialty board certification in vascular neurology. Dr Waters’ expertise is stroke and neurovascular disease, including signs, symptoms, diagnostics, and treatments. He is a fellow of both the American Academy of Neurology and American Heart Association and a member of the American Neurological Association, American Society of Human Genetics, and the Society of Vascular and Interventional Neurology. Dr Waters received his Masters in genetics from Penn State University in State College, Pennsylvania, USA, and his doctorate in biochemistry and molecular biology from The University of Florida College of Medicine in Gainesville, USA, where he also completed his MD. He completed his residency training at the University of California – Los Angeles Department of Neurology and completed his fellowship in clinical and molecular neurogenetics at Cedars Sinai Medical Center in Los Angeles, USA. Dr Waters’ research studies include genetic mechanisms of stroke, neuroprotection in stroke, stroke treatment, multiple clinical trials investigating stroke treatments, and neurogenetic mechanisms of neuroplasticity.

A comparison of statistical versus clinical classifiers of seizure clustering in women with catamenial and noncatamenial epilepsy.

We assessed whether (1) women with statistical clustering of daily seizure counts (DSCs) or seizure intervals (SIs) also showed clinical clustering, defined separately by ≥2 (≥2-SC) and ≥3 (≥3-SC) seizures on any single day; and (2) how these classifiers might apply to catamenial epilepsy. This is a retrospective case-control analysis of data from 50 women with epilepsy (WWE). We assessed the relationships of the four classifiers to each other and to catamenial versus noncatamenial epilepsy using chi-squared, correlation, logistic regression, and receiver operating characteristic (ROC) analyses. ≥3-SC, not ≥2-SC, was more frequent in WWE who had statistical DSC clustering versus those who did not (21/25 [84.0%] vs. 11/25 [44.0%], p= .007). Logistic regression (p= .006) and ROC (p= .015) identified ≥3-SC, not ≥2-SC, as a predictor of statistical DSC clustering, but ≥4-SC was more accurate. ≥3-SC correlated with the average daily seizure frequencies (ADSFs) of the subjects (p= .01). ROC optimal sensitivity-specificity cut-point for ADSF prediction of ≥3-SC (.372) was 64.6% higher than for ≥2-SC (.226). SI clustering was more common in WWE who had catamenial versus noncatamenial epilepsy (p= .013). Logistic regression identified statistical SI clustering as the only significant classifier (p= .043). ROC analysis offered only marginal support (p= .056), because specificity was low (42.1%). The findings lend statistical support for (1) the utility of clinical ≥3-SC as a predictor of convulsive status epilepticus, (2) consideration of ADSFs in defining clustering, and (3) ≥4-SC as a more accurate clinical predictor of statistical DSC clustering. Statistical SI clustering occurred more frequently in women with catamenial than noncatamenial epilepsy (90.3% vs. 57.9%, p= .013). Although sensitivity was high (90.3%, 28/31), specificity was only 42.1% (8/19). Algorithms that test patterns and periodicities of clusters are more applicable.

Mortality after a first-ever unprovoked seizure.

Although increased mortality associated with epilepsy is well understood, data in patients after their first-ever seizure are limited. We aimed to assess mortality after a first-ever unprovoked seizure and identify causes of death (CODs) and risk factors. A prospective cohort study was undertaken of patients with first-ever unprovoked seizure between 1999 and 2015 in Western Australia. Two age-, gender-, and calendar year-matched local controls were obtained for each patient. Mortality data, including COD, based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes, were obtained. Final analysis was performed in January 2022. One thousand two hundred seventy-eight patients with a first-ever unprovoked seizure were compared to 2556 controls. Mean follow-up was 7.3 years (range = .1-20). Overall hazard ratio (HR) for death after a first unprovoked seizure compared to controls was 3.06 (95% confidence interval [CI] = 2.48-3.79), with HRs of 3.30 (95% CI=2.26-4.82) for those without seizure recurrence and 3.21 (95% CI=2.47-4.16) after a second seizure. Mortality was also increased in patients with normal imaging and no identified cause (HR=2.50, 95% CI=1.82-3.42). Multivariate predictors of mortality were increasing age, remote symptomatic causes, first seizure presentation with seizure cluster or status epilepticus, neurological disability, and antidepressant use at time of first seizure. Seizure recurrence did not influence mortality rate. The commonest CODs were neurological, most relating to the underlying cause of seizures rather than being seizure-related. Substance overdoses and suicide were more frequent CODs in patients compared to controls and were commoner than seizure-related deaths. Mortality is increased two- to threefold after a first-ever unprovoked seizure, independent of seizure recurrence, and is not only attributable to the underlying neurological etiology. The greater likelihood of deaths related to substance overdose and suicide highlights the importance of assessing psychiatric comorbidity and substance use in patients with first-ever unprovoked seizure.

Criminal liability and epilepsy: a case report of a postictal attempted homicide from Tunisia.

Patients with epilepsy who have been charged with a serious offense may be referred by the courts for forensic psychiatric examination. A detailed psychiatric and neurological examination is often necessary to assist the courts in making the right decision, as exemplified in the current case presentation. The forensic case of a 30-year-old Tunisian male with temporal epilepsy who exhibited an inadequate response to the treatment is presented here. The patient attempted to kill his neighbor after a cluster of seizures, showing apparent postictal aggression. An antiepileptic treatment was introduced a few days after the person's detention and was followed by forensic psychiatric examination, but the latter was not done until three months afterwards. On forensic examination, the patient's thought processes were clear with no evidence of a thought disorder or psychosis. Both medical and psychiatric opinions stated that the attempted homicide was due to a postictal psychosis. The patient was transferred to a psychiatric facility for further management and was found not guilty by reason of insanity. This case illustrates the difficulties that experts may encounter in establishing criminal liability after aggressive behavior associated with epilepsy. It highlights shortcomings in Tunisian law (and promptness of forensic psychiatric examination) that should be addressed to ensure fairness of the legal process.

Stereoelectroencephalography Implantation Using Frameless Neuronavigation and Varioguide: Prospective Analysis of Accuracy and Safety in a Case Series of 11 Patients

Stereoencephalography (SEEG) is becoming a widespread diagnostic procedure for drug-resistant epilepsy investigation. Techniques include frame-based and robot-assisted implantation, and more recently, frameless neuronavigated systems (FNSs). Despite its recent use, the accuracy and safety of FNS are still under investigation. To assess in a prospective study the accuracy and safety of a specific FNS use for SEEG implantation. Twelve patients who underwent SEEG implantation using FNS (Varioguide [Brainlab]) were included in this study. Data were collected prospectively and included demographic data, postoperative complications, functional results, and implantation characteristics (i.e., duration and number of electrodes). Further analysis included accuracy at entry point and target using measurements of the euclidean distance between planned and actual trajectories. Eleven patients underwent SEEG-FNS implantation from May 2019 to March 2020. One patient did not undergo surgery because of a bleeding disorder. The mean target deviation was 4.06 mm, and mean entry point deviation was 4.2 mm, with insular electrodes significantly more deviated. Results excluding insular electrodes showed a mean target deviation of 3.66 mm and a mean entry point deviation of 3.77 mm. No severe complications occurred; a few mild to moderate adverse events were reported (1 superficial infection, 1 seizure cluster, and 3 transient neurologic impairments). The mean implantation duration by electrodes was 18.5 minutes. Implantation of depth electrodes for SEEG using FNS seems to be safe, but larger prospective studies are needed to validate these results. Accuracy is sufficient for noninsular trajectories but warrant caution for insular trajectories with statistically significantly less accuracy.

Efficacy of a pre-specified timeline-based treatment protocol in children with acute repetitive seizures or seizure clusters.

Acute repetitive seizures (ARSs) are one of the few commonly encountered neurological emergencies in children. There is a need for an appropriate timeline-based treatment protocol, which will be shown to be safe and efficacious in a clinical study. This was a retrospective chart review to determine the efficacy of a pre-specified treatment protocol for the management of ARSs in children aged 1-18 years. The treatment protocol was specifically applied in children with a diagnosis of epilepsy and not critically ill, who met the criteria for ARSs, with the exemption of new onset of ARSs. The first tier of treatment protocol focused on intravenous lorazepam, optimization of dose of existing anti-seizure medications (ASMs), and control of triggers like acute febrile illness, while second-tier focused on adding one or two additional ASMs, commonly used in cases with seizure clusters or status epilepticus. We included the first 100 consecutive patients (7.6 ± 3.2 years, 63% boys). Our treatment protocol was successful in 89 patients (58 and 31 required first-tier and second-tier treatment). The absence of pre-existing drug-resistant epilepsy and the presence of acute febrile illness as a triggering factor (P = 0.02 and 0.03) were associated with the success of the first tier of the treatment protocol. Excessive sedation (n = 29), incoordination (n = 14), transient gait instability (n = 11), and excessive irritability (n = 5) were the most common adverse effects observed during the initial 1 week. This pre-specified treatment protocol is safe and efficacious in controlling ARSs in cases with established epilepsy who are not critically sick. External validation from other parts of the world/centers and a more diverse epilepsy population are required before generalizing the protocol into clinical practice.

Prognosis of adults and children following a first unprovoked seizure.

Prognosis of adults and children following a first unprovoked seizure.

The Evaluation of the Efficacy and Safety of Midazolam Nasal Spray in Patients With Seizure Clusters: A Systematic Review and Meta-Analysis.

Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and clinical trials have shown that midazolam nasal spray could become an effective and promising alternative to conventional routes (intravenous {IV}/rectal). Therefore, we thought of conducting a systematic review and meta-analysis of midazolam (MDZ) to assess its potential outcomes. The analysis was also evaluated based on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of midazolam nasal spray. A systematic literature search was carried out through various databases to identify studies of accounted outcomes of midazolam nasal spray (MDZ-NS). Randomized and other studies of patients (12 years or older) with seizure clusters (SCs) were included. A total of three full-text articles were considered for systematic review and meta-analysis as per the inclusion and exclusion criteria. The 5 mg MDZ-NS was observed to be equally safe as a placebo, and the risk ratio (RR) was 1.01 (95% confidence interval (CI): 0.67-1.53). After the administration of MDZ-NS, either the patientsremained seizure-free for six hours or moreor the seizure was terminated within 10 minutes and had no recurrence between 10 minutes and six hours. The risk ratio (RR) obtained was 1.54 (95% CI: 1.25-1.91). The result was statistically significant as a higher success rate was observed with the use of 5 mg midazolam nasal spray compared to placebo (p < 0.0001). Heterogeneity was not observed in the results of the included studies (inconsistency index {I2}:0%). The present systematic review and meta-analysisdemonstrated that 5 mg midazolam nasal spray was efficacious in treating patients with seizure clustersand is well-tolerated. Also, its use is relatively safe.

Putative roles for homeostatic plasticity in epileptogenesis.

Homeostatic plasticity allows neural circuits to maintain an average activity level while preserving the ability to learn new associations and efficiently transmit information. This dynamic process usually protects the brain from excessive activity, like seizures. However, in certain contexts, homeostatic plasticity might produce seizures, either in response to an acute provocation or more chronically as a driver of epileptogenesis. Here, we review three seizure conditions in which homeostatic plasticity likely plays an important role: acute drug withdrawal seizures, posttraumatic or disconnection epilepsy, and cyclic seizures. Identifying the homeostatic mechanisms active at different stages of development and in different circuits could allow better targeting of therapies, including determining when neuromodulation might be most effective, proposing ways to prevent epileptogenesis, and determining how to disrupt the cycle of recurring seizure clusters.

Quality of life in dogs with idiopathic epilepsy and their owners with an emphasis on breed-A pilot study.

Epilepsy in dogs is a common chronic and serious disorder and may have an impact on the quality of life of the owners as well as the dogs themselves. The aim of this pilot study was to investigate the QoL score of dogs suffering from idiopathic epilepsy and their owners and if possible, investigate whether a breed specific difference exists. Owners, either Dutch or Belgium, were asked to participate in a web based SurveyMonkey questionnaire. A total of 402 questionnaires representing 402 dogs with epilepsy were suitable for further analysis. Of the 402 dogs, 253 were males and 149 were females. Ninety-nine different breeds were represented. Fourteen breeds (177 dogs in total) were used to calculate breed specific scores; Australian Shepherd (n = 8), Beagle (n = 7), Belgian Tervuren dog (n = 9), Belgian Groenendaeler dog (n = 8), Border Collie (n = 38), Chihuahua (n = 9), Dachshund (n = 13), Drentsche Patrijshond (a Dutch partridge dog) (n = 14), French Bulldog (n = 12), Golden Retriever (n = 17), Labrador Retriever (n = 18), and Rottweiler (n = 12). For the Border Collie, there was a statistically significant correlation between "epilepsy related death," the severity of the seizures (p < 0.001) and cluster seizures (p < 0.001). The quality of life of the Border Collie was scored lower compared to all other dogs (p = 0.02). There were three breeds that had a minimal decrease in the overall quality of life score compared to all other dogs: the Chihuahua (p = 0.03), Dachshund (p = 0.001), and Golden retriever (p = 0.01). The score for "caring for my epileptic dog decreases my own QoL" was high for the Border Collie, Boxer, French Bulldog, and Rottweiler, but was only found to be statistically significantly higher in the Border Collie (p = 0.01). Scores for the Golden Retriever (p = 0.04) and Labrador (p = 0.006) were lower. In conclusion, this study reports breed specific quality of life scores of dogs with epilepsy and their owners, and underlines that breed by itself, is also an important factor when managing epilepsy in dogs.

Genetic generalized epilepsy: factors associated with drug resistance polytherapy

BackgroundDifferent studies investigating generalized genetic epilepsy (GGE) have shown that achieving 5 years of remission, early seizure remission, and needing antiseizure medication (ASM) monotherapy may predict favorable long-term outcomes.ResultsThis is a retrospective analytical cohort study. Records of patients with GGE diagnoses at a large epilepsy center in Cairo served as the data source. 630 patients (297 male patients (47.1%) and 333 female (52.9%)) were included, their median onset age was 13 years. The follow-up period of this study was at least 4 years. 418 patients (66.1%) were early remitters, 160 patients (25.4%) were late remitters, and 52 patients (8.3%) were intractable. In addition, 367 patients (58.3%) needed a single ASM to achieve a maximum remission period (monotherapy group), while 263 patients (41.7%) needed ASM polytherapy. Stepwise regression analysis revealed that absence seizures, clusters of seizures, seizure frequency before treatment, and dose of sodium valproate (VPA) until the first remission were independent predictors for polytherapy. Moreover, absence seizures, seizure frequency before treatment, VPA dose, and catamenial seizures in females were independent predictors of intractability.ConclusionThe majority of GGE have a favorable outcome, some clinical features could predict the need for polytherapy and failure of remission on treatment.

What is the safe observation period for seizure recurrence in pediatric emergency departments?

BackgroundAfebrile seizures are the common causes of emergency department (ED) admissions in childhood, and there is limited data on the observation period in emergency service follow-up of these patients in terms of seizure recurrence in the literature. This study aims to determine the seizure recurrence time in afebrile seizures and the risk factors that determine it. MethodsPatients aged between 1 month and 18 years with afebrile seizures were included in the study. Seizure recurrence times, demographic data, diagnosis of epilepsy, use of antiseizure medications, Electroencephalography (EEG) and imaging results, structural abnormalities, hospitalizations, and treatments were recorded. ResultsThe median age of 623 patients included in the study was 42 months (16.0–94.0 months) and 59.9% were male. Epilepsy was diagnosed in 372 (59.7%) of the patients. Short-acting benzodiazepine was administered in 249 of the cases. The mean observation time of the patients was 36 hours (24–98 hours). Electroencephalography (EEG) was applied in 437 (70.1%) of the patients and abnormality was detected in 53.5%. Seizure recurrence was observed in 149 patients (23.9%). The median time of seizure recurrence was 1.0 hour (0.5–4.0 hours). Eighty-six percent of the seizure recurrences (n = 129) occurred within the first six hours and 95.3% (n = 142) within the first 12 hours. Risk factors included a history of febrile seizures (p = 0.001, OR = 2.7), not receiving short-acting benzodiazepine therapy (p = 0.026, OR 1.7), previous structural abnormalities (p = 0.018, OR 1.8), and cluster seizures (p = 0.001, OR 6.7) for all patients and also EEG abnormalities in pediatric ED for first seizure (p = 0.012, OR 2.4). ConclusionPatients with a history of febrile seizure, previous structural abnormalities, cluster seizures, EEG abnormalities in pediatric ED, and patients who didn’t receive BZD treatment were at risk for seizure recurrence in the early period. Since most seizure recurrences occur within the first 6 hours, this period is the most critical time for recurrence risk.

The nose has it: Opportunities and challenges for intranasal drug administration for neurologic conditions including seizure clusters.

Nasal administration of treatments for neurologic conditions, including rescue therapies to treat seizure clusters among people with epilepsy, represents a meaningful advance in patient care. Nasal anatomy and physiology underpin the multiple advantages of nasal administration but also present challenges that must be addressed in any successful nasal formulation. Nasal cavity anatomy is complex, with a modest surface area for absorption that limits the dose volume of an intranasal formulation. The mucociliary clearance mechanism and natural barriers of the nasal epithelia must be overcome for adequate absorption. An extensive vasculature and the presence of olfactory nerves in the nasal cavity enable both systemic and direct-to-brain delivery of drugs targeting the central nervous system. Two intranasal benzodiazepine rescue therapies have been approved by the US Food and Drug Administration for seizure-cluster treatment, in addition to the traditional rectal formulation. Nasal sprays are easy to use and offer the potential for quick and consistent bioavailability. This review aims to increase the clinician's understanding of nasal anatomy and physiology and of the formulation of intranasal rescue therapies and to facilitate patient education and incorporate intranasal rescue therapies for seizure clusters (also known as acute repetitive seizures) into their seizure action plans.

Early onset developmental and epileptic encephalopathy and Rett-like phenotype in a 15-year-old girl affected by Cornelia de Lange syndrome type 2 due to a SMC1A gene mutation

Developmental and epileptic encephalopathies (DEE) are conditions in which a mutated gene may cause abnormal functioning of the central nervous system, resulting in both encephalopathy and epileptogenesis. We present a case of a girl with a DEE characterized by a Rett-like phenotype in association with febrile and afebrile clusters of focal seizures. The girl presented typical development until the age of 18 months, followed by regression. The first febrile bilateral tonic-clonic seizure was observed at 30 months of age, and the following month seizures recurred in clusters of several episodes per day every 10 days. These seizures were characterized by behavioural arrest, emotional symptoms, head turning, and followed by bilateral tonic-clonic seizures. The administration of valproic acid and levetiracetam led to prolonged seizure control. However, from the age of 7 years, she had monthly recurrent clusters of focal seizures and non-convulsive status epilepticus which occurred at different ages. Brain and spinal cord MRI showed mild non-progressive hemispheric cerebellar atrophy. A next generation sequencing panel for epilepsy identified the de novo splicing mutation c.2973+1G>A of the SMC1A gene.

Effects of phenobarbital, potassium bromide and topiramate on intractable epilepsies in two cases of holoprosencephaly

We describe the courses of treatment for epilepsies in two patients with semilobar type holoprosencephaly (HPE); a 5-year-old girl and a 30-year-old man. Seizure semiology included eye fixation, upward or lateral gaze, horizontal or vertical nystagmus, eyelid flutter, and grinning facial distortion, which frequently evolved to generalized tonic convulsions. In both patients, ictal electroencephalography revealed seizure onset with rhythmic activity in bilateral frontopolar areas. Administration of phenobarbital with subsequent elevation of blood levels to 30–40 μg/ml alleviated the clustered tonic seizures. This allowed dosage reduction of other antiepileptic drugs that had sedative and/or respiratory adverse effects causing significant distress in these patients. Potassium bromide 20–50 mg/kg/day and topiramate 1–3 mg/kg/day were also beneficial in these patients. A combination regimen of these three antiepileptic drugs could be a promising treatment option for intractable epilepsy in HPE.

Use of intranasal rescue therapy for seizure clusters in students with epilepsy: Nurses’ knowledge, perceptions, and practice

Use of intranasal rescue therapy for seizure clusters in students with epilepsy: Nurses’ knowledge, perceptions, and practice