Epilepsy is a common disease, affecting approximately 0.5% of the US population, and disproportionately affecting children. Often, seizures develop months or years - the 'latent period' - following an initial brain injury, such as an episode of SE in early childhood. Not all individuals with comparable early life SE, however, develop epilepsy. Indeed, only a minority of children at risk subsequently develops epilepsy. To prospectively select children most likely to benefit from antiepileptogenic therapy it is necessary to identify surrogate markers. The recent advances in neuroimaging suggest that it may be possible to use neuroimaging tools to identify these surrogate markers. Identification of surrogate markers and would make it possible to initiate antiepileptogenic therapies only in children at risk. Furthermore, since it may take years before seizures develop following an injury, the identification of neuroimaging markers predicting epilepsy can accelerate the discovery of appropriate age-specific treatments to prevent epilepsy Thus, additional surrogate markers must be identified. To be of greatest use, markers either should persist through the latent period or should appear at distinct times within the latent period. It is also desirable that these markers provide insight into the evolution of the biological processes that culminate in epilepsy. To circumvent the problem of long latent periods in the development of human epilepsy, we propose to identify surrogate markers of epileptogenesis in lithium-pilocarpine immature rat model of epilepsy where seizures develop on average ten weeks after status epilepticus. By prospectively studying rats using magnetic resonance imaging and spectroscopy methods, we propose to identify brain changes that precede and predict the development of epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS048149-02
Application #
7140449
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Fureman, Brandy E
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2006-07-01
Budget End
2008-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$224,912
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Tschuluun, N; Hall, W M; Mulloney, B (2009) State-changes in the swimmeret system: a neural circuit that drives locomotion. J Exp Biol 212:3605-11
Smarandache, Carmen; Hall, Wendy M; Mulloney, Brian (2009) Coordination of rhythmic motor activity by gradients of synaptic strength in a neural circuit that couples modular neural oscillators. J Neurosci 29:9351-60
Lado, Fred A; Moshe, Solomon L (2008) How do seizures stop? Epilepsia 49:1651-64
Mulloney, Brian; Hall, Wendy M (2007) Not by spikes alone: responses of coordinating neurons and the swimmeret system to local differences in excitation. J Neurophysiol 97:436-50
Mulloney, Brian; Hall, Wendy M (2007) Local and intersegmental interactions of coordinating neurons and local circuits in the swimmeret system. J Neurophysiol 98:405-13
Djukic, Aleksandra; Lado, Fred A; Shinnar, Shlomo et al. (2006) Are early myoclonic encephalopathy (EME) and the Ohtahara syndrome (EIEE) independent of each other? Epilepsy Res 70 Suppl 1:S68-76
Mulloney, Brian; Harness, Patricia I; Hall, Wendy M (2006) Bursts of information: coordinating interneurons encode multiple parameters of a periodic motor pattern. J Neurophysiol 95:850-61
Mulloney, Brian (2005) A method to measure the strength of multi-unit bursts of action potentials. J Neurosci Methods 146:98-105