title: A model of symptomatic infantile spasms syndrome.
abstract: Infantile spasms are characterized by age-specific expression of epileptic spasms and hypsarrhythmia and often result in significant cognitive impairment. Other epilepsies or autism often ensue especially in symptomatic IS (SIS). Cortical or subcortical damage, including white matter, have been implicated in the pathogenesis of SIS. To generate a model of SIS, we recreated this pathology by injecting rats with lipopolysaccharide and doxorubicin intracerebrally at postnatal day (P) 3 and with p-chlorophenylalanine intraperitoneally at P5. Spasms occurred between P4 and 13 and were associated with ictal EEG correlates, interictal EEG abnormalities and neurodevelopmental decline. After P9 other seizures, deficits in learning and memory, and autistic-like behaviors (indifference to other rats, increased grooming) were observed. Adrenocorticotropic hormone (ACTH) did not affect spasms. Vigabatrin transiently suppressed spasms at P5. This new model of SIS will be useful to study the neurobiology and treatment of SIS, including those that are refractory to ACTH.
authors: Saul R. Korey Department of Neurology, Laboratory of Developmental Neurology, and Montefiore/Einstein Epilepsy Management Center, USA. moscantl@montefiore.org
authors: Morris H
authors: MH
authors: Scantlebury
authors: Aristea S
authors: AS
authors: Galanopoulou
authors: Lenka
authors: L
authors: Chudomelova
authors: Emmanuel
authors: E
authors: Raffo
authors: David
authors: D
authors: Betancourth
authors: Solomon L
authors: SL
authors: Moshé
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000927:Anticonvulsants / Q000494:pharmacology; D001321:Autistic Disorder / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D001925:Brain Damage, Chronic / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D004351:Drug Resistance / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D010134:Fenclonine / Q000633:toxicity; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012702:Serotonin Antagonists / Q000633:toxicity; D013036:Spasms, Infantile / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology*; D020888:Vigabatrin / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D000927:Anticonvulsants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012702:Serotonin Antagonists; D004317:Doxorubicin; D000324:Adrenocorticotropic Hormone; D020888:Vigabatrin; D010134:Fenclonine