Guidance on Dravet syndrome from infant to adult care: Road map for treatment planning in Europe

Cardenal‐Muñoz, Elena; Auvin, Stéphane; Villanueva, Vicente; Cross, J. Helen; Zuberi, Sameer M.; Lagae, Lieven; Aibar, José Ángel

doi:10.1002/epi4.12569

Cited by 46 publications

(50 citation statements)

References 116 publications

(105 reference statements)

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“…A case study of an infant with partial deletion of chromosome 2 which includes SCN1A described severe seizures as well as pulmonary emphysema [Takatsuki, et al 2009]. Additionally, respiratory tract infections are a prevalent co-morbidity, affecting almost half of DS patients [Cardenal-Munoz, et al 2021; Schubert-Bast, et al 2022]. Though direct respiratory characteristics have yet to be assessed in DS, our results and clinical reports support lung structure and function in this population as a contributor to respiratory dysfunction.…”

Section: Discussionsupporting

confidence: 57%

Breathing dysfunction and alveolar damage in a mouse model of Dravet syndrome

Goh

Deering-Rice

Nguyen

et al. 2022

Preprint

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SUMMARYObjectiveThe incidence of Sudden Unexpected Death in Epilepsy (SUDEP) is especially high in those with Dravet syndrome (DS). Risk factors have been identified, but the mechanism(s) by which death occurs is not fully understood. Evidence supports ventilatory dysfunction in the pathophysiology of SUDEP. Understanding specific respiratory patterns present at baseline and after seizures at different ages, as well as the health of lung tissue, will allow us to better understand how sudden death occurs in this population.MethodsWhole body plethysmography (WBP) was used to monitor respiration before and after electrically induced seizure in the Scn1aA1783V/WT mouse model of DS weekly for a period of four weeks. Following the four-week WBP study, lungs from surviving animals were collected and stained with hematoxylin and eosin and Weigert’s elastin and the density of tissue and elastin were analyzed.ResultsBreathing was diminished in the DS mouse at baseline and following evoked seizures in younger aged mice (P18-P24), consistent with prolonged post-ictal inspiratory time and low respiratory drive compared to the response seen in older animals. In older DS mice, consisting of those that have survived a critical period for mortality, the response to seizure was more robust and included higher respiratory drive, peak inspiratory and expiratory flow rates, tidal and expiratory volumes, and breathing frequency compared to wild-type and relative to baseline. Alveolar damage was also observed in P46-P52 DS mice.SignificanceDifferences in specific respiratory parameters in younger DS animals, during the time when mortality is greatest, compared to older DS animals (i.e. those that have survived the critical period) may allow us to better understand respiratory differences contributing to SUDEP. Lung tissue damage in DS may also contribute to respiratory dysfunction in SUDEP.KEY POINTSBaseline respiration is diminished in DS mice compared to wild type.Electrically induced seizure produced a different respiratory response in younger DS mouse compared to older DS animals.Alveolar septal damage is present in DS mice.Baseline and post-ictal breathing dysfunction and inefficient oxygenation and CO2 clearance likely potentiated by lung damage may serve as a potential mechanism by which SUDEP occurs in DS.

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Section: Discussionsupporting

confidence: 57%

Breathing dysfunction and alveolar damage in a mouse model of Dravet syndrome

Goh

Deering-Rice

Nguyen

et al. 2022

Preprint

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“…Cannabidiol may also be utilized (in Europe with clobazam). If an individual is on combination therapy and cannabidiol becomes unavailable clobazam dose should be increased by one-quarter 52 .…”

Section: Dravet Syndromementioning

confidence: 99%

Recommendations for treatment strategies in people with epilepsy during times of shortage of antiseizure medications

Asadi‐Pooya¹,

Patel²,

Trinka³

et al. 2022

Epileptic Disorders

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In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains) management of people with epilepsy (PWE) with available ASMs can be difficult. A group of experts, brought together by the International League Against Epilepsy (ILAE), to formulate recommendations for such circumstances. Every effort was made to base these recommendations on direct published literature or extrapolations from basic information available about ASMs. Actual published literature in this area is however limited and at times, assumptions were made by the experts to generate these recommendations. During times of shortage of ASMs, switching between different ASMs (e.g., oxcarbazepine and carbamazepine) can occasionally be considered as a mitigation procedure. However, for many ASMs, the option of an overnight switch to another drug does not exist. Switching from brand to generic or between generic products has often been shown to be safe, if required. Finally, when supplies of benzodiazepines or equipment to administer medications intravenously are not available, rectal administration of some ASMs may be an emergency alternative route for treating serial seizures and status epilepticus. Decisionmaking with regard to treatment and possible options should be driven by what is best for the patient.

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“…hyperactivity and inattention TAND, e.g. range of cognitive, behavioural and psychiatric manifestations including intellectual disability, ASD, ADHD, anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations a A number of ASMs should be avoided for DS because they may exacerbate seizures, especially in children, sodium channel blockers (carbamazepine, eslicarbazepine acetate, lacosamide, lamotrigine, oxcarbazepine and phenytoin) and ASMs that act on GABA pathways (tiagabine, vigabatrin, gabapentin and pregabalin) b As specified in recent treatment guidance/reviews for DS [ 3 , 5 , 15 – 17 ], LGS [ 18 – 21 ] and TSC [ 2 , 22 – 26 ] c Predominantly in Germany and Japan d Licenced in the USA; undergoing regulatory approval in the European Union e Being evaluated for preventative treatment Bold indicates licenced in the USA and/or European Union…”

Section: Introductionmentioning

confidence: 99%

“…b As specified in recent treatment guidance/reviews for DS [ 3 , 5 , 15 – 17 ], LGS [ 18 – 21 ] and TSC [ 2 , 22 – 26 ]…”

Section: Introductionmentioning

confidence: 99%

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

Strzelczyk

Schubert‐Bast

2022

CNS Drugs

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The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox–Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous h...

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Guidance on Dravet syndrome from infant to adult care: Road map for treatment planning in Europe

Cited by 46 publications

References 116 publications

Breathing dysfunction and alveolar damage in a mouse model of Dravet syndrome

Breathing dysfunction and alveolar damage in a mouse model of Dravet syndrome

Recommendations for treatment strategies in people with epilepsy during times of shortage of antiseizure medications

Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies

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