Perception of impact of Dravet syndrome on children and caregivers in multiple countries: looking beyond seizures

Nabbout, Rima; Auvin, Stéphane; Chiron, Catherine; Thiele, Elizabeth A.; Cross, Helen; Scheffer, Ingrid E.; Schneider, Amy; Guerrini, Renzo; Williamson, Nicola; Irwin, J. David; Mistry, Arun; Grimes, Richard; Bennett, Bryan

doi:10.1111/dmcn.14186

Cited by 47 publications

(90 citation statements)

References 34 publications

(69 reference statements)

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“…It is acknowledged that, in addition to seizures, many other clinical problems—including cognitive impairment, behavioral disorders, and a number of comorbidities—characterize the disease course. Recent studies have underscored that these comorbidities are the most disabling symptoms in long‐term outcome . The analysis of our series confirms that ID and behavioral disorders with the ensuing impairment of adaptive functioning causes a remarkable burden for the families.…”

Section: Discussionsupporting

confidence: 77%

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

et al. 2019

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To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group 2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course.At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age.Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy. K E Y W O R D Sadolescents and adults, complete Dravet syndrome, developmental and epileptic encephalopathy, longterm outcome, myoclonic phenotype, reflex seizures S50 | DARRA et Al.

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Section: Discussionsupporting

confidence: 77%

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

et al. 2019

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“…DS has a significant impact on both patients' and caregivers' lives . We identified core domains to measure the impact on both patients and caregivers dealing with DS . Although seizures were the most commonly reported symptom in DS, many additional issues critically impact on patients’ cognitive and behavioral functioning, as attested to by both caregivers and physicians.…”

Section: Dravet Syndrome: Core Concepts Beyond Seizuresmentioning

confidence: 99%

“…The five major domains of concern from French caregivers and health care professionals were the following: seizures, expressive communication and receptive communication of the child, impact on daily activities, and social functioning of the caregiver . This study was followed by further analysis of this conceptual disease model in four additional countries: the United States, the UK, Italy, and Australia . Themes identified showed similarity with the French conceptual model, with minor differences between countries that likely reflect variations in health care systems.…”

Section: Dravet Syndrome: Core Concepts Beyond Seizuresmentioning

confidence: 99%

SCN1A‐related phenotypes: Epilepsy and beyond

2019

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SCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with several epilepsy syndromes and a range of other diseases. SCN1A represents the archetypal channelopathy associated with a wide phenotypic spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). SCN1A disorders also result in other diseases such as hemiplegic migraine and autism spectrum disorder (ASD). Dravet syndrome (DS) is the prototypic DEE with an early onset of febrile status epilepticus, hemiclonic or generalized tonic‐clonic seizures, and later onset of additional seizure types. Electroencephalography (EEG) and magnetic resonance imaging (MRI) are normal at onset. Development is normal in the first year of life but plateaus rapidly, with most patients ultimately having intellectual disability. Epilepsy is drug‐resistant and necessitates polytherapy. Most pathogenic variants occur de novo in the affected child, but they are inherited from mosaic affected or unaffected parents in rare cases. The molecular finding of haploinsufficiency is consistent with a loss‐of‐function defect in cells and animal models. Although seizures are the most commonly reported symptom in DS, many additional issues critically affect patients’ cognitive and behavioral functioning. Hemiplegic migraine (HM) is a rare form of migraine with aura, characterized by the emergence of hemiparesis as part of the aura phase. All SCN1A mutations reported in sporadic/familial HM3 are missense mutations. Most of the experimental results show that they cause a gain of function of NaV1.1 as opposed to the loss of function of the epileptogenic NaV1.1 mutations. SCN1A and SCN2A pathogenic variants have been identified in genetic studies of cohorts of patients with ASD. In addition, ASD features are often reported in patients with Dravet syndrome and other DEEs.

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“…Several studies shows a substantial worldwide issue of diagnostic delay of DS, with a mean age at diagnosis that is usually over two years, resulting in "unnecessary, costly, and, at times, invasive testing, and use of ineffective therapies, which can exacerbate seizures, increase the risk of status epilepticus, and worsen cognitive outcome". (17,(35)(36)(37) Moreover, DS is certainly less recognized in adult population and in developing countries. (19,20) Computer-based models using EHRs able to suggest diagnosis/avoid misdiagnosis are gaining ground.…”

Section: Discussionmentioning

confidence: 99%

Improving Early Diagnosis of Rare Diseases Using Natural Language Processing in Unstructured Medical Records: An Illustration From Dravet Syndrome 

Barco

Kuchenbuch

Garcelon

et al. 2021

Preprint

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BackgroundThe growing use of Electronic Health Records (EHRs) is promoting the application of data mining in health-care. A promising use of big data in this field is to develop models to support early diagnosis and to establish natural history. Dravet Syndrome (DS) is a rare Developmental and Epileptic Encephalopathy that commonly initiates in the first year of life with febrile seizures (FS). Age at diagnosis is often delayed after two years, as it is difficult to differentiate DS at onset from FS.We aimed to explore if some clinical terms (concepts) are significantly more used in the electronic narrative medical reports of individuals with DS before the age of two years compared to those of individuals with FS. These concepts would allow an earlier detection of patients with DS resulting in an earlier orientation toward expert centers that can provide early diagnosis and care.MethodsData were collected from the Necker Enfants Malades Hospital using a document-based data warehouse, Dr Warehouse, which employs Natural Language Processing, a computer technology consisting in processing written information. Using Unified Medical Language System Meta-thesaurus, phenotype concepts can be recognized in medical reports. We selected individuals with DS (DS Cohort) and individuals with FS (FS Cohort) with confirmed diagnosis after the age of four years. A phenome-wide analysis was performed evaluating the statistical associations between the phenotypes of DS and FS, based on concepts found in the reports produced before two years and using a series of logistic regressions. ResultsWe found significative higher representation of concepts related to seizures’ phenotype distinguishing DS from FS in the first phases, namely the major recurrence of complex febrile convulsions (long-lasting and/or with focal signs) and other seizure-types. Some typical early onset non-seizure concepts also emerged, in relation to neurodevelopment and gait disorders. ConclusionsNarrative medical reports of individuals younger than two years with FS contain specific concepts linked to DS diagnosis, which can be automatically detected by software exploiting NLP. This approach could represent an innovative and sustainable methodology to decrease time of diagnosis of DS and could be transposed to other rare diseases.

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Perception of impact of Dravet syndrome on children and caregivers in multiple countries: looking beyond seizures

Abstract: DEEDevelopmental and epileptic encephalopathy HRQoLHealth-related quality of life AIM To assess the relevance and generalizability across countries of concepts of the impact of Dravet syndrome beyond seizures, as recognized by families.

Cited by 47 publications

References 34 publications

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

SCN1A‐related phenotypes: Epilepsy and beyond

Improving Early Diagnosis of Rare Diseases Using Natural Language Processing in Unstructured Medical Records: An Illustration From Dravet Syndrome

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Perception of impact of Dravet syndrome on children and caregivers in multiple countries: looking beyond seizures

Abstract: DEEDevelopmental and epileptic encephalopathy HRQoLHealth-related quality of life AIM To assess the relevance and generalizability across countries of concepts of the impact of Dravet syndrome beyond seizures, as recognized by families.

Cited by 47 publications

References 34 publications

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

SCN1A‐related phenotypes: Epilepsy and beyond

Improving Early Diagnosis of Rare Diseases Using Natural Language Processing in Unstructured Medical Records: An Illustration From Dravet Syndrome&nbsp;

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Improving Early Diagnosis of Rare Diseases Using Natural Language Processing in Unstructured Medical Records: An Illustration From Dravet Syndrome