In Search of Epilepsy Biomarkers in the Immature Brain: Goals, Challenges and Strategies

Galanopoulou, Aristea S.; Moshé, Solomon L.

doi:10.2217/bmm.11.71

Cited by 44 publications

(42 citation statements)

References 87 publications

(91 reference statements)

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“…In addition, the future serial EEGs obtained as part of FEBSTAT along with MRIs and clinical follow-up may serve as biomarkers for the development of epilepsy. [26][27][28] …”

Section: -24mentioning

confidence: 99%

Acute EEG findings in children with febrile status epilepticus

et al. 2012

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Objective: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study is prospectively addressing the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus (FSE). Methods:We recruited 199 children with FSE within 72 hours of presentation. Children underwent a detailed history, physical examination, MRI, and EEG within 72 hours. All EEGs were read by 2 teams and then conferenced. Associations with abnormal EEG were determined using logistic regression. Interrater reliability was assessed using the k statistic.Results: Of the 199 EEGs, 90 (45.2%) were abnormal with the most common abnormality being focal slowing (n 5 47) or attenuation (n 5 25); these were maximal over the temporal areas in almost all cases. Epileptiform abnormalities were present in 13 EEGs (6.5%). In adjusted analysis, the odds of focal slowing were significantly increased by focal FSE (odds ratio [OR] 5 5.08) and hippocampal T2 signal abnormality (OR 5 3.50) and significantly decreased with high peak temperature (OR 5 0.18). Focal EEG attenuation was also associated with hippocampal T2 signal abnormality (OR 5 3.3).Conclusions: Focal EEG slowing or attenuation are present in EEGs obtained within 72 hours of FSE in a substantial proportion of children and are highly associated with MRI evidence of acute hippocampal injury. These findings may be a sensitive and readily obtainable marker of acute injury associated with FSE. Neurology Febrile status epilepticus (FSE) is an important neurologic emergency and the most severe type of complex febrile seizure. Acute morbidity and mortality are low, 1 but the long-term consequences of FSE and risks of specific epilepsies, such as mesial temporal epilepsy, are not well established. Retrospective studies report that approximately 30% of patients with medically refractory temporal lobe epilepsy being evaluated for surgery have a history of prolonged febrile seizures, but prospective studies failed to confirm the association.2-9 The Consequences of Prolonged Febrile Seizures (FEB-STAT) study is designed to prospectively examine the outcome of FSE and predictors of outcome. 10Both MRI and EEG data are collected within 72 hours and then at later intervals to evaluate the possible relationship of FSE to subsequent mesial temporal lobe epilepsy. The methodology of assembling the cohort and a description of the clinical semiology and phenomenology of the first 119 subjects were previously published. 10 In this report, we describe the acute EEG findings and their relationship to characteristics of the episode of FSE as well as to the acute imaging findings. 11,13 A febrile seizure was defined as a provoked seizure in which the sole acute provocation was fever (temperature .38.4°C, 101.0°F) without history of a febrile seizure and with no evidence of an acute CNS infection or insult.11,13 Children with known severe neurologic disability before entry were excluded from the FEBSTAT study. Subjects were e...

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“…In addition, the future serial EEGs obtained as part of FEBSTAT along with MRIs and clinical follow-up may serve as biomarkers for the development of epilepsy. [26][27][28] …”

Section: -24mentioning

confidence: 99%

Acute EEG findings in children with febrile status epilepticus

et al. 2012

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“…Past early-identification of DRE is mainly based on clinical manifestations like the number of seizures [19]. Other than applying the well-established electroencephalography (EEG) monitoring, other imaging testsing and clinical symptoms and signs watching, DRE urgently requires a set of molecular biomarkers to clarify the early prognosis, wherein microRNAs play an important role [20][21][22].…”

Section: Drug-resistant Epilepsy: Definition and Prognosismentioning

confidence: 99%

“…Similar to miRNA in tumorigenesis, miRNAs exhibit a dual role in epileptogenesis-neuroprotection or induce neural cell death. A large number of studies have shown that the occurrence of epilepsy with nerve cells apoptosis, Synaptic connections reconstruction, glial fibers cell hyperplasia, abnormal pathways is closely related to the formation and inflammatory response [20,21]. Repeated seizures can result in hippocampus neuron apoptosis in brain, the abnormal formation excitatory synapses loop, and ultimately improve the intractable temporal lobe epilepsy [23,24].…”

Section: Pathogenetic Mechanisms Of Mirna-mediated Epileptogenesismentioning

confidence: 99%

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

et al. 2016

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MicroRNA (miRNA) is a type of endogenous non-coding RNA that can regulate cell proliferation, differentiation, invasion, apoptosis and several other biological activities by specially inducing gene silencing, and thereby is related to development and disease in life course. In recent years, researchers have found that miRNAs are closely related with refractory epilepsy. MiRNAs can intervene in the modification of mRNAs, the synthesis of proteins and some the connectivity of signal pathways in pathogenesis of epilepsy. Furthermore, some miRNAs in neurons are of great importance in neuronal differentiation. Therefore, miRNA may play a very important role in the occurrence, development and episodes of refractory epilepsy. These discoveries can provide a new direction for the research of pathogenesis, diagnostic methods and therapeutic approach of refractory epilepsy. Although research about miRNA and intractable epilepsy has progressed, more remains to be done before miRNA can be used in clinical diagnosis and treatment strategies. This paper focuses on the research progress of molecular diagnosis about miRNA in intractable epilepsy.

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“…However, across-species comparisons of brain growth, DNA, cholesterol, and water content suggested that PN8 -10 rats are more closely related to full-term human newborns (Gottlieb et al 1977;Dobbing and Sands 1979), although eye opening does not occur until PN13 -15 and rodent pups are able to ambulate and run during the third week of life, unlike most infants. In reality, different developmental processes mature at different tempos across species, making definite equivalency rules difficult to generalize (Avishai-Eliner et al 2002;Galanopoulou and Moshé 2011). In this review, we will mostly refer to models that show epilepsy during the first 3 wk of life (thought of as equivalent to neonatal and infantile age) or have been constructed with the intent to recreate human neonatal and infantile epilepsies.…”

Section: Developmental Equivalency Across Speciesmentioning

confidence: 99%

Neonatal and Infantile Epilepsy: Acquired and Genetic Models

Galanopoulou

Moshé

2015

Cold Spring Harb Perspect Med

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The incidence of seizures and epilepsies is particularly high during the neonatal and infantile periods. We will review selected animal models of early-life epileptic encephalopathies that have addressed the dyscognitive features of frequent interictal spikes, the pathogenesis and treatments of infantile spasms (IS) or Dravet syndrome, disorders with mammalian target of rapamycin (mTOR) dysregulation, and selected early-life epilepsies with genetic defects. Potentially pathogenic mechanisms in these conditions include interneuronopathies in IS or Dravet syndrome and mTOR dysregulation in brain malformations, tuberous sclerosis, and related genetic disorders, or IS of acquired etiology. These models start to generate the first therapeutic drugs, which have been specifically developed in immature animals. However, there are challenges in translating preclinical discoveries into clinically relevant findings. The advances made so far hold promise that the new insights may potentially have curative or disease-modifying potential for many of these devastating conditions. T he neonatal and infantile periods show relatively high age-adjusted incidence of epilepsy compared with other ages of life (Hauser et al. 1993). The etiology of newly diagnosed epilepsies at these ages also is distinct, showing greater representation of epilepsies of unknown, genetic, or congenital etiologies (Hauser et al. 1993). The semiology and syndromic phenotypes of epilepsies that first appear in this early life period are also distinct and often more fulminant, appearing with evident neurodevelopmental problems or regression (e.g., epileptic encephalopathies) or characteristic seizure types (e.g., infantile spasms [IS], multifocal clonic seizures) ( Table 1). In addition, the treatments for epilepsies of these age groups can be specialized, as is the case with the use of hormonal therapies (e.g., adrenocorticotropic hormone [ACTH] in certain epileptic encephalopathies). Given the serious repercussions for the development of these neonates and infants and the importance of finding better therapies with disease-modifying potential, several efforts have been made to create animal models of these conditions to increase our understanding and ability to treat them. Here, we will review selected animal models, genetic or induced, that address epilepsies and epileptic encephalopathies characteristic of neonates and infants.

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In Search of Epilepsy Biomarkers in the Immature Brain: Goals, Challenges and Strategies

Cited by 44 publications

References 87 publications

Acute EEG findings in children with febrile status epilepticus

Acute EEG findings in children with febrile status epilepticus

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

Neonatal and Infantile Epilepsy: Acquired and Genetic Models

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