OBJECTIVE: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). METHODS: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. RESULTS: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. CONCLUSIONS: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.
OBJECTIVE: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). METHODS: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. RESULTS: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CDpatients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. CONCLUSIONS:Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasiapatients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosispatients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.
Authors: Carlos Cepeda; Véronique M André; Jason S Hauptman; Irene Yamazaki; My N Huynh; Julia W Chang; Jane Y Chen; Robin S Fisher; Harry V Vinters; Michael S Levine; Gary W Mathern Journal: Neurobiol Dis Date: 2011-08-23 Impact factor: 5.996
Authors: Carlos Cepeda; Véronique M André; Irene Yamazaki; Jason S Hauptman; Jane Y Chen; Harry V Vinters; Gary W Mathern; Michael S Levine Journal: Epilepsia Date: 2010-07 Impact factor: 5.864
Authors: Ingmar Blümcke; Maria Thom; Eleonora Aronica; Dawna D Armstrong; Harry V Vinters; Andre Palmini; Thomas S Jacques; Giuliano Avanzini; A James Barkovich; Giorgio Battaglia; Albert Becker; Carlos Cepeda; Fernando Cendes; Nadia Colombo; Peter Crino; J Helen Cross; Olivier Delalande; François Dubeau; John Duncan; Renzo Guerrini; Philippe Kahane; Gary Mathern; Imad Najm; Ciğdem Ozkara; Charles Raybaud; Alfonso Represa; Steven N Roper; Noriko Salamon; Andreas Schulze-Bonhage; Laura Tassi; Annamaria Vezzani; Roberto Spreafico Journal: Epilepsia Date: 2010-11-10 Impact factor: 5.864
Authors: Maria Thom; Sofia Eriksson; Lillian Martinian; Luis O Caboclo; Andrew W McEvoy; John S Duncan; Sanjay M Sisodiya Journal: J Neuropathol Exp Neurol Date: 2009-08 Impact factor: 3.685
Authors: Laura C Armstrong; Grant Westlake; John P Snow; Bryan Cawthon; Eric Armour; Aaron B Bowman; Kevin C Ess Journal: Hum Mol Genet Date: 2017-12-01 Impact factor: 6.150