The long-range objective of this research is to define the relationship between sleep and the electroencephalographic (EEG) manifestations of epilepsy in humans so that targeted therapeutic interventions to treat sleep-related seizures may be developed. Cellular neurophysiological studies suggest that processes underlying the initiation and deepening of non-rapid eye movement (NREM) sleep, including progressive hyperpolarization in thalamocortical projection neurons, induce a state of relative neuronal synchronization associated with the facilitation of interictal and ictal activity. In partial epilepsy, interictal epileptiform discharges (IEDs) are more prevalent in delta NREM sleep and as sleep is deepening. The proposed experiments will test the hypotheses that generalized IEDs and sleep-related epileptic seizures are also activated by neurophysiological processes underlying the initiation and deepening of NREM sleep. Sleep depth will be measured by the quantity of delta activity in the EEG.
In Specific Aim 1, 120 subjects with partial or generalized epilepsy will undergo EEG-polysomnography in the General Clinical Research Center to characterize the relationship of IEDs to sleep state, sleep depth, and arousals from sleep.
In Specific Aim 2, the relationship of epileptic seizures to sleep state, sleep depth, and arousals from sleep will be defined in 120 additional subjects with sleep-related seizures undergoing monitoring with continuous EEG recordings as part of their epilepsy surgery evaluation. Multivariate analogs of logistic regression models will be applied to these data to determine the predictive value of sleep state, sleep depth, and arousals from sleep on IED and seizure occurrence. The training aspects of this career development proposal will (1) broaden the principal investigator's education in clinical research, specifically the statistical analysis of longitudinal data; (2) strengthen her expertise in the application of signal analysis techniques to the sleep EEG; (3) facilitate her development of a research team; and (4) enhance her clinical and teaching expertise in sleep neuroscience and epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02NS002099-04
Application #
6529069
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
1999-09-01
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
4
Fiscal Year
2002
Total Cost
$132,300
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Neurology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Marzec, Mary L; Selwa, Linda M; Malow, Beth A (2005) Analysis of the first night effect and sleep parameters in medically refractory epilepsy patients. Sleep Med 6:277-80
Jessup, Stacy K; Malow, Beth A; Symons, Kathleen V et al. (2004) Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep. Eur J Endocrinol 151:561-6
Malow, Beth A (2004) Sleep disorders, epilepsy, and autism. Ment Retard Dev Disabil Res Rev 10:122-5
Malow, Beth A; Weatherwax, Kevin J; Chervin, Ronald D et al. (2003) Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: a prospective pilot study. Sleep Med 4:509-15
Lagrange, A H; Blaivas, M; Gomez-Hassan, D et al. (2003) Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult. Epilepsy Behav 4:788-92
Marzec, Mary; Edwards, Jonathan; Sagher, Oren et al. (2003) Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients. Epilepsia 44:930-5
Weatherwax, Kevin J; Lin, Xihong; Marzec, Mary L et al. (2003) Obstructive sleep apnea in epilepsy patients: the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) is a useful screening instrument for obstructive sleep apnea in a disease-specific population. Sleep Med 4:517-21
Malow, B A; Passaro, E; Milling, C et al. (2002) Sleep deprivation does not affect seizure frequency during inpatient video-EEG monitoring. Neurology 59:1371-4
Minecan, Daniela; Natarajan, Alamelu; Marzec, Mary et al. (2002) Relationship of epileptic seizures to sleep stage and sleep depth. Sleep 25:899-904
Malow, B A; Edwards, J; Marzec, M et al. (2001) Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients. Neurology 57:879-84

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