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Article ; Online: Dravet Syndrome: Don't Hesitate, Just Vaccinate!

Nickels, Katherine C / Wirrell, Elaine C

2022 Volume 100, Issue 4, Page(s) 171–173

MeSH term(s)	Humans ; Epilepsies, Myoclonic/genetics ; Vaccination/adverse effects
Language	English
Publishing date	2022-11-02
Publishing country	United States
Document type	Editorial
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000201531
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Article: Dravet Syndrome as an Example of Precision Medicine in Epilepsy.

Sullivan, Joseph / Wirrell, Elaine C

Epilepsy currents

2022 Volume 23, Issue 1, Page(s) 4–7

Abstract: Dravet syndrome (DS) is a drug-resistant, early-onset, developmental and epileptic encephalopathy where there have been many recently approved therapies with many more in development. With the availability of more syndrome specific treatment options ... ...

Abstract	Dravet syndrome (DS) is a drug-resistant, early-onset, developmental and epileptic encephalopathy where there have been many recently approved therapies with many more in development. With the availability of more syndrome specific treatment options coupled with an earlier diagnosis, DS is well-positioned to be an example of how a precise syndromic diagnosis can guide treatment choices and improve overall outcomes and also allow for the development of potential disease modifying therapies to address more than just seizures. In this review we summarize the current state of DS approved therapies and those that are in various stages of development.
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2270080-8
ISSN	1535-7597
ISSN	1535-7597
DOI	10.1177/15357597221106281
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Article ; Online: An Update on Stiripentol Mechanisms of Action: A Narrative Review.

Bacq, Alexandre / Depaulis, Antoine / Castagné, Vincent / Le Guern, Marie-Emmanuelle / Wirrell, Elaine C / Verleye, Marc

Advances in therapy

2024 Volume 41, Issue 4, Page(s) 1351–1371

Abstract: Stiripentol ( ... ...

Abstract	Stiripentol (Diacomit
MeSH term(s)	Humans ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Dioxolanes/pharmacology ; Dioxolanes/therapeutic use ; Seizures/drug therapy ; Epilepsies, Myoclonic/drug therapy ; gamma-Aminobutyric Acid
Chemical Substances	Anticonvulsants ; stiripentol (R02XOT8V8I) ; Dioxolanes ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-024-02813-0
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Article ; Online: Discontinuing Antiseizure Medication in Neonates With Acute Symptomatic Seizures-Primum non nocere.

Payne, Eric T / Wirrell, Elaine C

JAMA neurology

2021 Volume 78, Issue 7, Page(s) 797–799

MeSH term(s)	Anticonvulsants/therapeutic use ; Humans ; Infant, Newborn ; Seizures/drug therapy
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2021-06-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2021.1218
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Article ; Online: Stiripentol for the treatment of seizures associated with Dravet syndrome in patients 6 months and older and taking clobazam.

Vasquez, Alejandra / Wirrell, Elaine C / Youssef, Paul E

Expert review of neurotherapeutics

2023 Volume 23, Issue 4, Page(s) 297–309

Abstract: Introduction: Stiripentol (STP) is a structurally unique molecule with anticonvulsant and neuroprotective properties in animal and human studies. STP enhances gamma-aminobutyric acid (GABA)ergic neurotransmission and inhibits multiple hepatic isoenzymes ...

Abstract	Introduction: Stiripentol (STP) is a structurally unique molecule with anticonvulsant and neuroprotective properties in animal and human studies. STP enhances gamma-aminobutyric acid (GABA)ergic neurotransmission and inhibits multiple hepatic isoenzymes (i.e. cytochrome P450 system) involved in the metabolism of other antiseizure medications (ASMs) potentiating their anticonvulsant effects and has proven to be a promising therapy in Dravet Syndrome (DS). Areas covered: The authors review randomized clinical trials and observational studies showing STP efficacy, safety, and tolerability when used as adjunctive therapy with VPA and clobazam in patients with DS. Moreover, they include recent evidence of its use in patients<2 years of age. Expert opinion: Evidence on STP demonstrates clinically meaningful efficacy in both short and long term in patients with DS. In addition to reducing convulsive seizure frequency, STP also markedly reduces the number of status epilepticus episodes and associated medical complications which are more common in younger children. STP adverse effects are generally not severe and often resolve following STP dose reduction or adjustments of concomitant ASMs. STP is approved by the FDA for children aged 6 months and older with DS who are also taking clobazam, making it the only DS-specific ASM for children under age 1 year.
MeSH term(s)	Child ; Child, Preschool ; Humans ; Anticonvulsants/pharmacology ; Clobazam/therapeutic use ; Epilepsies, Myoclonic/drug therapy ; Epilepsies, Myoclonic/complications ; Seizures/drug therapy ; Seizures/etiology ; Randomized Controlled Trials as Topic ; Observational Studies as Topic
Chemical Substances	Anticonvulsants ; Clobazam (2MRO291B4U) ; stiripentol (R02XOT8V8I)
Language	English
Publishing date	2023-03-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112534-X
ISSN	1744-8360 ; 1473-7175
ISSN (online)	1744-8360
ISSN	1473-7175
DOI	10.1080/14737175.2023.2195550
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Article ; Online: Pediatric psychogenic non-epileptic seizures: A retrospective observational cohort study at a quaternary center.

Vasquez, Alejandra / Hilliker, Daniel R / Wirrell, Elaine C

Epilepsy & behavior : E&B

2023 Volume 146, Page(s) 109359

Abstract: Background: Psychogenic non-epileptic seizures (PNES) represent a common functional disorder in the pediatric population. We aimed to characterize pediatric PNES by describing their clinical characteristics, PNES semiologies, and healthcare pathway ... ...

Abstract	Background: Psychogenic non-epileptic seizures (PNES) represent a common functional disorder in the pediatric population. We aimed to characterize pediatric PNES by describing their clinical characteristics, PNES semiologies, and healthcare pathway towards and after diagnosis. Material and methods: This was a retrospective, observational chart review of pediatric patients aged 6 to 18 years admitted between December 2020 and December 2021 for spell classification or suspected PNES. Psychogenic non-epileptic seizure diagnosis was made by the capture of a typical event on video electroencephalogram (vEEG). We used descriptive statistics to summarize demographic and clinical characteristics. Results: We included 26 patients (18 females, 69.2%) with a mean age (SD) of 13.9 (2.5) years. Pre-morbid neurologic and psychiatric conditions included: epilepsy (23.1%), migraine (46.2%), mild traumatic brain injury (26.9%), anxiety (57.7%), ADHD (34.6%), and depression (30.8%). Six patients (23.1%) had a prior diagnosis of PNES. 14 patients (53.8%) presented with convulsive, and 6 (23.1%) each with non-convulsive and mixed PNES. Patients were seen by a range of providers prior to diagnosis including ED providers (50%), neurologists (53.8%), pediatricians (34.6%), and psychology/psychiatry (11.5%). Emergency department evaluation occurred for 13 patients (50%) on 15 occasions, and six (23.1%) were admitted to the hospital. The median (p25-p75) time from PNES onset to presentation and diagnosis at our institution was 3.5 (1.5-6.2) and 4.1 (3-7) months, respectively. A total of 33 events from the 26 patients were captured on vEEG. The most frequent semiologies in our cohort were rhythmic motor (27.3%) followed by equal frequency (18.2%) of complex motor and dialeptic. Eighteen patients (69.2%) were followed after the PNES diagnosis, for a median (p25-p75) of 17.3 months (6.3-21) with variable outcome. Conclusion: Pediatric PNES has female predominance and often presents with comorbid psychosocial stressors and psychiatric conditions. High clinical suspicion and early recognition are crucial to decrease healthcare utilization and establish timely diagnosis and treatment.
MeSH term(s)	Humans ; Child ; Female ; Adolescent ; Male ; Retrospective Studies ; Psychophysiologic Disorders/complications ; Psychophysiologic Disorders/diagnosis ; Psychophysiologic Disorders/epidemiology ; Seizures/diagnosis ; Seizures/epidemiology ; Seizures/drug therapy ; Epilepsy/psychology ; Comorbidity ; Electroencephalography
Language	English
Publishing date	2023-07-25
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2023.109359
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Article ; Online: Drug resistance in epilepsy.

Perucca, Emilio / Perucca, Piero / White, H Steve / Wirrell, Elaine C

The Lancet. Neurology

2023 Volume 22, Issue 8, Page(s) 723–734

Abstract: Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated ... ...

Abstract	Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated neurological deficits. Although drug-resistant epilepsy is not synonymous with unresponsiveness to any drug treatment, the probability of achieving seizure freedom on a newly tried medication decreases with increasing number of previously failed treatments. After two appropriately used antiseizure medications have failed to control seizures, individuals should be referred whenever possible to a comprehensive epilepsy centre for diagnostic re-evaluation and targeted management. The feasibility of epilepsy surgery and other treatments, including those targeting the cause of epilepsy, should be considered early after diagnosis. Substantial evidence indicates that a delay in identifying an effective treatment can adversely affect ultimate outcome and carry an increased risk of cognitive disability, other comorbidities, and premature mortality. Research on mechanisms of drug resistance and novel therapeutics is progressing rapidly, and potentially improved treatments, including those targeting disease modification, are on the horizon.
MeSH term(s)	Humans ; Anticonvulsants/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/diagnosis ; Seizures/drug therapy ; Treatment Outcome ; Drug Resistant Epilepsy/drug therapy ; Drug Resistance
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2023-06-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2081241-3
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(23)00151-5
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Article ; Online: How have the recent updated epilepsy classifications impacted on diagnosis and treatment?

Wirrell, Elaine C / Riney, Kate / Specchio, Nicola / Zuberi, Sameer M

Expert review of neurotherapeutics

2023 Volume 23, Issue 11, Page(s) 969–980

Abstract: Introduction: Epilepsies are a diverse group of disorders which differ regarding prognosis for seizure control and associated comorbidities. Accurate classification is critical to choose the highest yield investigations and best therapeutic options and ... ...

Abstract	Introduction: Epilepsies are a diverse group of disorders which differ regarding prognosis for seizure control and associated comorbidities. Accurate classification is critical to choose the highest yield investigations and best therapeutic options and to provide the most accurate prognoses regarding the expected degree of seizure control, possible remission, and risk of associated comorbidities to patients and their families. This article reviews the recent updates in epilepsy classification to illustrate how accurate classification impacts care for persons with epilepsy. Areas covered: The authors discuss the ILAE 2017 Classification of the Epilepsies along with the modification of the classification for neonatal seizures and epilepsies. They also discuss the ILAE position papers on Epilepsy syndromes in neonates and infants and children of variable age and the Idiopathic Generalized Epilepsies. Expert opinion: Accurate epilepsy classification allows selection of the highest yield investigations, choice of optimal therapies, and accurate prognostication of seizures (likelihood of response to antiseizure treatments and likelihood of remission with age), as well as comorbidities (likelihood, type, and severity). As we move into the era of disease modifying therapy, early accurate identification of underlying causes with timely introduction of specific treatments will be crucial to lessen the severity of epilepsy, with improved seizure control and attenuation of associated comorbidities.
MeSH term(s)	Child ; Infant ; Infant, Newborn ; Humans ; Epilepsy/diagnosis ; Epilepsy/therapy ; Seizures/diagnosis ; Epilepsy, Generalized ; Comorbidity ; Prognosis
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2112534-X
ISSN	1744-8360 ; 1473-7175
ISSN (online)	1744-8360
ISSN	1473-7175
DOI	10.1080/14737175.2023.2254937
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Article ; Online: Autism Spectrum Disorder and Epilepsy.

Kwon, Churl-Su / Wirrell, Elaine C / Jetté, Nathalie

Neurologic clinics

2022 Volume 40, Issue 4, Page(s) 831–847

Abstract: Autism spectrum disorder (ASD), was first described in 1943 as a disorder consisting of a triad of qualitative impairments of social interaction, communication and restricted repetitive patterns of behavior, interests, and activities. The relationship ... ...

Abstract	Autism spectrum disorder (ASD), was first described in 1943 as a disorder consisting of a triad of qualitative impairments of social interaction, communication and restricted repetitive patterns of behavior, interests, and activities. The relationship between ASD and epilepsy is well documented. Patients with ASD have an increased risk of epilepsy, while those with epilepsy have a higher risk of ASD, as compared with the general population. Diagnosing epilepsy in those with ASD can be challenging. For example, stereotyped behaviors could be mistaken as ASD stereotypies, when in fact, they may be due to seizures. Fortunately, in recent years, we have gained a better understanding of the best antiseizure medications (ASMs) to use in this vulnerable population. However, more studies are needed to understand how best to screen for ASD in epilepsy, what the various ASD phenotypes are in people with epilepsy, especially those due to de novo genes/mutations, as well as factors influencing the fluctuating nature of ASD symptoms (eg, seizure type, frequency, syndromes, ASMs)..
MeSH term(s)	Humans ; Autism Spectrum Disorder/complications ; Autism Spectrum Disorder/diagnosis ; Autism Spectrum Disorder/epidemiology ; Epilepsy/diagnosis ; Epilepsy/drug therapy ; Epilepsy/epidemiology ; Seizures ; Phenotype
Language	English
Publishing date	2022-09-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1013148-6
ISSN	1557-9875 ; 0733-8619
ISSN (online)	1557-9875
ISSN	0733-8619
DOI	10.1016/j.ncl.2022.03.011
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Article ; Online: Impact of Antiseizure Medications on Appetite and Weight in Children.

Buraniqi, Ersida / Dabaja, Hicham / Wirrell, Elaine C

Paediatric drugs

2022 Volume 24, Issue 4, Page(s) 335–363

Abstract: There are numerous potential factors that may affect growth in children with epilepsy, and these must be evaluated in any child with appetite and weight concerns. Antiseizure medications (ASMs) have potential adverse effects, and many may affect appetite, ...

Abstract	There are numerous potential factors that may affect growth in children with epilepsy, and these must be evaluated in any child with appetite and weight concerns. Antiseizure medications (ASMs) have potential adverse effects, and many may affect appetite, thus impacting normal growth and weight gain. The aim of this review is to focus on the impact of both epilepsy and ASMs on appetite and weight in children. We systematically reviewed studies using Medline assessing the impact of ASMs on appetite and weight in children. Eligible studies included randomized controlled trials and open-label studies (open-label extension and interventional) that targeted or included the pediatric population (0-18 years of age). Each study was classified using the American Academy of Neurology (AAN) Classification of Evidence for Therapeutic Studies, and the level of evidence for impact on appetite and weight in children was graded. ASMs associated with decreased appetite and/or weight loss include fenfluramine, topiramate, zonisamide, felbamate, rufinamide, stiripentol, cannabidiol, brivaracetam and ethosuximide; ASMs with minimal impact on weight and appetite in children include oxcarbazepine, eslicarbazepine, lamotrigine, levetiracetam, lacosamide, carbamazepine, vigabatrin and clobazam. The ASM most robustly associated with increased appetite and/or weight gain is valproic acid; however, both pregabalin and perampanel may also lead to modest weight gain or increased appetite in children. Certain ASMs may impact both appetite and weight, which may lead to increased morbidity of the underlying disease and impaired adherence to the treatment regimen.
MeSH term(s)	Anticonvulsants/adverse effects ; Appetite ; Child ; Epilepsy/drug therapy ; Humans ; Lamotrigine/therapeutic use ; Weight Gain
Chemical Substances	Anticonvulsants ; Lamotrigine (U3H27498KS)
Language	English
Publishing date	2022-05-21
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1492748-2
ISSN	1179-2019 ; 1174-5878
ISSN (online)	1179-2019
ISSN	1174-5878
DOI	10.1007/s40272-022-00505-2
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