Pathophysiology of Catastrophic Epileptic Syndromes
Catastrophic epilepsies are a group of age-related epileptic syndromes characterized by a variety of behavioral seizure manifestations, malignant EEG patterns, and dismal outcomes including profound psychomotor arrest or regression. They can either be symptomatic or cryptogenic in origin and the etiology may be acquired or genetically based. The prognosis is grave as many patients progress to develop other intractable seizure types, severe cognitive impairments, and even death often independent of the underlying etiology. Because the catastrophic epilepsies are associated with devastating outcomes, it is important to improve the understanding of the pathophysiological substrates underlying these conditions. This is dependent on the development of novel, syndrome specific, animal models systems that can be used to study mechanisms and develop safe, effective, nontoxic treatments. This review will focus on the leading hypotheses governing the mechanisms for seizure...
KeywordsCorticotrophin Release Hormone GABAB Receptor Infantile Spasm Epileptic Encephalopathy Tonic Seizure
Supported by NIH NINDS grants NS20253, NS045243, NS58303, NS62947, and grants from the International Rett Syndrome Foundation and PACE.
- Chudomelova L, Scantlebury MH, Raffo E, Coppola A, Betancourth D, Galanopoulou AS (2010) Modeling new therapies for infantile spasms. Epilepsia (in press)Google Scholar
- Kagawa K, Chugani DC, Asano E, Juhasz C, Muzik O, Shah A, Shah J, Sood S, Kupsky WJ, Mangner TJ, Chakraborty PK, Chugani HT (2005) Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET). J Child Neurol 20:429–438CrossRefPubMedGoogle Scholar
- Marsh E, Fulp C, Gomez E, Nasrallah I, Minarcik J, Sudi J, Christian SL, Mancini G, Labosky P, Dobyns W, Brooks-Kayal A, Golden JA (2009) Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. Brain 132:1563–1576CrossRefPubMedGoogle Scholar
- Panayiotopoulos CP (2010) A clinical guide to epileptic syndromes and their treatment, Revised 2nd edn. Springer, LondonGoogle Scholar
- Price MG, Yoo JW, Burgess DL, Deng F, Hrachovy RA, Frost JD Jr, Noebels JL (2009) A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. J Neurosci 29:8752–8763CrossRefPubMedGoogle Scholar
- Wallace RH, Hodgson BL, Grinton BE, Gardiner RM, Robinson R, Rodriguez-Casero V, Sadleir L, Morgan J, Harkin LA, Dibbens LM, Yamamoto T, Andermann E, Mulley JC, Berkovic SF, Scheffer IE (2003) Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology 61:765–769PubMedGoogle Scholar