Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Silva, M. L.; Cieuta, Cécile; Guerrini, Renzo; Plouin, Perrine; Livet, Marie-Odile; Dulac, Olivier

doi:10.1111/j.1528-1157.1996.tb00535.x

Cited by 50 publications

(54 citation statements)

References 14 publications

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“…However, the data do suggest that the Ts65Dn mouse (39) holds great promise as a substrate for a chronic model to help unravel the pathogenesis of infantile spasms and lead to the identification of novel therapeutic targets for this devastating disorder. There are no published data on the use of ESM in the treatment of infantile spasms; however, the marked efficacy of ESM in this model system suggests that this drug might be efficacious in the treatment of infantile spasms in children with Down syndrome (8). Finally, our data suggest that GABA B R-mediated mechanisms should be added to the list of putative mechanisms involved in epileptogenesis in infantile spasms (40).…”

Section: Discussionmentioning

confidence: 96%

Infantile Spasms and Down Syndrome: A New Animal Model

Cortez

Shen

et al. 2009

Pediatr Res

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Infantile spasms is a catastrophic childhood seizure disorder for which few animal models exist. Children with Down syndrome are highly susceptible to infantile spasms. The Ts65Dn mouse is a valid model for Down syndrome; therefore, we tested the hypothesis that the Ts65Dn mouse represents a substrate for an animal model of infantile spasms. The baseline of naïve Ts65Dn mice showed spontaneous spike-and-wave discharges, a pattern that worsened with baclofen and ␥-butyrolactone, which induced acute epileptic extensor spasms (AEES) associated with epileptiform polyspike bursts and an electrodecremental response on the EEG. GABA B R-agonist-induced AEES were significantly reduced with vigabatrin, rodent ACTH fragment, valproic acid, ethosuximide, and CGP 35348. Porcine ACTH had no effect. GABA B R protein expression was significantly increased in the thalamus and medulla oblongata of Ts65D mice in comparison with wild-type controls. The GABA B R agonist-treated Ts65Dn mouse shows the unique clinical, electrographic, and pharmacologic signature of infantile spasms and represents a valid, acute model of this disorder. GABA B R-mediated mechanisms may contribute to the increased susceptibility of children with Down syndrome to infantile spasms. (Pediatr Res 65: 499-503, 2009)

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Section: Discussionmentioning

confidence: 96%

Infantile Spasms and Down Syndrome: A New Animal Model

Cortez

Shen

et al. 2009

Pediatr Res

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“…Conspicuous or "loud" factors that could interfere with the assessment of cognitive improvement during drug treatment include differences in baseline global or linguistic function (Abbeduto et al 2008;Chapman et al 1998) and sufficiency of hearing and vision (Austeng et al 2013;Cregg et al 2003;Felius et al 2014;John et al 2004;Libb et al 1985;Suttle and Lloyd 2005;Woodhouse et al 2000), along with any personal history of neurological events such as infantile spasms (Eisermann et al 2003;Silva et al 1996), epilepsy (Arya et al 2011;Goldberg-Stern et al 2001), or sleep apnea (Rosen 2011). In the sections that follow, we will discuss a few "silent" factors that are not usually considered.…”

Section: Early-onset Hypothyroidismmentioning

confidence: 98%

Assessing Cognitive Improvement in People with Down Syndrome: Important Considerations for Drug-Efficacy Trials

Fernandez

Reeves

2015

Cognitive Enhancement

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Experimental research over just the past decade has raised the possibility that learning deficits connected to Down syndrome (DS) might be effectively managed by medication. In the current chapter, we touch on some of the work that paved the way for these advances and discuss the challenges associated with translating them. In particular, we highlight sources of phenotypic variability in the DS population that are likely to impact performance assessments. Throughout, suggestions are made on how to detect meaningful changes in cognitive-adaptive function in people with DS during drug treatment. The importance of within-subjects evaluation is emphasized.

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“…The incidence of epilepsy is age related, peaking in the first year and again in decades 4-5 (198). The early peak is related to perinatal medical complications and an unusually high incidence of infantile spasms (199,200). Seizure occurrence later in life coincides with the development of Alzheimer-like neuropathologic changes (201,202).…”

Section: Down Syndromementioning

confidence: 99%

Recent Advances in the Genetics of Epilepsy: Insights from Human and Animal Studies

Prasad

Stafstrom

1999

Epilepsia

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Summary: Progress in understanding the genetics of epilepsy is proceeding at a dizzying pace. Due in large part to rapid progress in molecular genetics, gene defects underlying many of the inherited epilepsies have been mapped, and several more are likely to be added each year. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, and correlate these advances with rapidly expanding information about the mechanisms of epilepsy gained from both spontaneous and transgenic animal models. We also provide practical suggestions for clinicians confronted with families in which multiple members are afflicted with epilepsy. Key Words: Epilepsy-GeneticsHuman-Pathophysiology-Animal models.Over the past few years, there has been an explosion of information about the genetic basis of epilepsy and epilepsy syndromes. Some of these advances have been documented in recent reviews (1-6). In parallei with advances in understanding the genetics of human epilepsies, several spontaneous and transgenic animal models of inherited epilepsy have been produced. These approaches will expand our ability to dissect cellular mechanisms of seizure generation and propagation and help us to move from serendipity to rationality in designing targeted therapies for seizure disorders (7,8). In this review we summarize the recent progress in mapping genes for human epilepsy, describe some relevant animal models of genetic epilepsy, and examine the relation between gene defects and the cellular mechanisms of epilepsy. Finally, we provide practical suggestions for clinicians caring for patients and families with inherited epilepsies. Clinical details of the various epilepsy syndromes, available elsewhere, are largely omitted here.Epilepsy, characterized by recurrent seizures, results from excessive synchronous firing of neurons in cortical networks. A number of intricately linked mechanisms at the network, cellular, subcellular, and molecular levels

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Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Cited by 50 publications

References 14 publications

Infantile Spasms and Down Syndrome: A New Animal Model

Infantile Spasms and Down Syndrome: A New Animal Model

Assessing Cognitive Improvement in People with Down Syndrome: Important Considerations for Drug-Efficacy Trials

Recent Advances in the Genetics of Epilepsy: Insights from Human and Animal Studies

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