This prospective study will determine if uncontrolled seizures over time impair development by comparing measures of morphometry, cognition, thought disorder, and psychopathology in 6 - 18 year old children with complex partial seizure disorder (CPS), primary generalized epilepsy with absences (PGE), and normal children at baseline and 2 years later. By including nonepileptic siblings of the CPS, PGE, and normal subjects, the project will ascertain if the hypothesized developmental abnormalities in the patients are epilepsy-related rather than familial.
Specific Aims : The study will test 3 main hypotheses: (a) CPS and PGE patients with an increase in seizure frequency from baseline through the 2 year follow-up will have a drop in IQ and an associated increase in thought disorder and psychopathology compared to patients with a decrease in seizure frequency and the normal subjects. (b) The patients with an increase in seizure frequency will have a smaller age-related increase in mesial temporal lobe (i.e., hippocampus, amygdala) and frontal lobe white matter volumes than the patients with a decrease in seizure frequency and the normal subjects. (c) The smaller age-related increase in mesial temporal lobe and frontal lobe white matter volumes will be associated with the predicted drop in IQ, and increase in thought disorder and psychopathology in the patients with uncontrolled seizures. Significance: By addressing the on-going debate """"""""Do seizures impair development?"""""""" the study's findings will delineate neurobiologic mechanisms of impaired cognition, thought disorder, and psychopathology in middle childhood epilepsy. They will underscore the importance of medical control of seizures to promote optimal development of cognition, communication, and behavior in these children. They will highlight the potential use of MRI for identifying children at risk for thought disorder and pave the way for future studies on treatment and prevention of thought disorder and psychopathology in pediatric CPS and PGE. Research Design and Methods: The study mill recruit 40 CPS, 40 PGE, and 40 normal children matched on age, gender, ethnicity, and socioeconomic status. Twenty-five siblings of the CPS, PGE, and normal subjects will also participate in the study. Each subject will undergo an MRI, as well as cognitive, thought disorder, behavioral, and linguistic testing at baseline and 2 years later. Weekly seizure frequency data will be obtained on a monthly basis from the parent during the 2 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS032070-05A2
Application #
6051750
Study Section
Special Emphasis Panel (ZRG1-BBBP-6 (01))
Program Officer
Jacobs, Margaret
Project Start
1999-09-30
Project End
2004-07-31
Budget Start
1999-09-30
Budget End
2000-07-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Jones, Jana E; Siddarth, Prabha; Almane, Dace et al. (2016) Identification of risk for severe psychiatric comorbidity in pediatric epilepsy. Epilepsia 57:1817-1825
Hua, Xue; Thompson, Paul M; Leow, Alex D et al. (2013) Brain growth rate abnormalities visualized in adolescents with autism. Hum Brain Mapp 34:425-36
Addis, Laura; Lin, Jack J; Pal, Deb K et al. (2013) Imaging and genetics of language and cognition in pediatric epilepsy. Epilepsy Behav 26:303-12
Lin, Jack J; Siddarth, Prabha; Riley, Jeffrey D et al. (2013) Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities. Epilepsia 54:2116-24
Jones, Jana E; Siddarth, Prabha; Gurbani, Suresh et al. (2013) Screening for suicidal ideation in children with epilepsy. Epilepsy Behav 29:521-6
Clark, Kristi; Narr, Katherine L; O'Neill, Joseph et al. (2012) White matter integrity, language, and childhood onset schizophrenia. Schizophr Res 138:150-6
Kernan, Claudia L; Asarnow, Robert; Siddarth, Prabha et al. (2012) Neurocognitive profiles in children with epilepsy. Epilepsia 53:2156-63
Seese, Ronald R; O'Neill, Joseph; Hudkins, Matthew et al. (2011) Proton magnetic resonance spectroscopy and thought disorder in childhood schizophrenia. Schizophr Res 133:82-90
O'Neill, Joseph; Seese, Ronald; Hudkins, Matthew et al. (2011) 1H MRSI and social communication deficits in pediatric complex partial seizures. Epilepsia 52:1705-14
Tosun, Duygu; Dabbs, Kevin; Caplan, Rochelle et al. (2011) Deformation-based morphometry of prospective neurodevelopmental changes in new onset paediatric epilepsy. Brain 134:1003-14

Showing the most recent 10 out of 38 publications