Models for infantile spasms: An arduous journey to the holy grail…

Baram, Tallie Z.

doi:10.1002/ana.21075

Cited by 26 publications

(24 citation statements)

References 27 publications

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“…Human studies provide some support for these hypotheses (Baram et al., 1992b), but animal models are required to further the understanding of the pathophysiology of IS, to study pathogenic mechanisms, and to develop and test new treatments (Baram, 1993, 2007; Scantlebury et al., 2007; Stafstrom, 2009). Due to its multiple etiologies, there are challenges in the development of a model for IS (Baram, 2007). The great number of etiologies in symptomatic IS suggests that there may be common pathways involved (Baram, 1993; Hrachovy & Frost, 2008).…”

Section: Pathophysiology Of Ismentioning

confidence: 99%

“…When considering common mechanisms or pathways in IS models, there are two potential mechanisms proposed in the pathogenesis of IS—increased excitability and loss of inhibition. The stress/corticotropin‐releasing hormone (CRH) hypothesis proposes that the common mechanism in all of the etiologies of IS causes an increase in the release of stress‐activated mediators in the brain, especially the neuropeptide CRH in limbic and brainstem regions in patients with IS (Baram, 2007). CRH causes seizures in developing rodents (Baram et al., 1992a; Baram & Schultz, 1995).…”

Section: Pathophysiology Of Ismentioning

confidence: 99%

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Infantile spasms: A U.S. consensus report

et al. 2010

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SUMMARYThe diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence-based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families-the Infantile Spasms Working Group (ISWG)-was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first-line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.

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Section: Pathophysiology Of Ismentioning

confidence: 99%

Section: Pathophysiology Of Ismentioning

confidence: 99%

Infantile spasms: A U.S. consensus report

et al. 2010

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“…Importantly, ACTH significantly increased the latency to onset of the spasms. While the model does not totally mimic the human condition [109], the model has considerable potential for screening AEDs.…”

Section: Infantile Spasmsmentioning

confidence: 99%

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Holmes¹,

Zhao²

2008

Pediatric Neurology

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Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy has been directed primarily toward reducing excitability through blockage of voltage-gated Na + or Ca 2+ channels, or increasing inhibition through enhancement of γ-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals, usually rodents. Maximal electrical shock, pentylenetetrazol, and kindling are typically used as non-mechanistic screens for antiseizure properties and the rotorod test for assessing acute toxicity. While antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it should be emphasized that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than adults. Despite these age-related unique features, drugs used in children are generally the same as used in adults. As awareness of the unique features of seizures during development increases, it is anticipated that more drug screening in the immature animal will occur.

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“…ACTH administration downregulates the secretion of CRF and other stress hormones. ACTH is thought to act directly on melanotropic receptors in the amygdala (Baram et al, 1992; Brunson et al., 2001; Rho, 2004; Baram, 2007). In a recent animal model of IS, prenatal betamethasone exposure sensitizes rats to development of N ‐methyl‐ d ‐aspartate–induced spasms and, most importantly, renders the spasms sensitive to ACTH therapy (Velisek et al, 2007).…”

mentioning

confidence: 99%

Insulin‐like growth factor‐1 is associated with cognitive outcome in infantile spasms

2010

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and yHUSLAB, Helsinki, Finland SUMMARY Purpose: The molecular mechanisms that lead to longterm consequences of infantile spasms (IS) are poorly understood. Insulin-like growth factor-1 (IGF-1) is regulated by insults that might be stressful to the brain, and is crucial for early brain development. The aim of the present study was to correlate cerebrospinal fluid (CSF) levels of IGF-1 with antecedent insults and cognitive outcome. Methods: We studied CSF IGF-1 and the adrenocorticotropic hormone (ACTH) concentrations in infants with idiopathic IS (IIS), symptomatic IS (SIS), and controls. Results: Infants with IIS had CSF IGF-1 concentrations similar to those of the control children, but children with SIS had markedly low CSF IGF-1 concentrations. In addition, CSF ACTH concentrations were significantly lower in the children with SIS than in those with IIS. High CSF IGF-1 concentrations were associated with an idiopathic etiology, absence of early (pre-or perinatal) insults or stress, normal brain imaging studies, good response to ACTH therapy, and favorable cognitive outcome. Low CSF IGF-1 concentrations were associated with low CSF ACTH concentrations, a history of early insults or stress, cerebral atrophy, poor response to therapy, and poor cognitive outcome. Discussion: In children with IS, insults or stress in early life may affect the synthesis of IGF-1, which might play a role in the reduction of certain cognitive functions.

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Models for infantile spasms: An arduous journey to the holy grail…

Cited by 26 publications

References 27 publications

Infantile spasms: A U.S. consensus report

Infantile spasms: A U.S. consensus report

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Insulin‐like growth factor‐1 is associated with cognitive outcome in infantile spasms

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