This grant application for an early randomized surgical epilepsy trial (ERSET) was originally prepared with the help of planning grant R21 NS37897, awarded in recognition of the fact that mesial temporal lobe epilepsy (MTLE) is a surgically remediable syndrome, that surgical treatment for this disorder is underutilized, and that true equipoise exists concerning the relative benefits of surgery vs. continued treatment with new antiepileptic drugs, early in the course of the disorder. We now submit a revised proposal for a multicenter randomized controlled trial (RCT) to compare the efficacy of early surgical intervention for MTLE with continued optimal pharmacotherapy. The primary outcome measure will be freedom from disabling epileptic seizures (complex partial and secondarily generalized seizures, and simple partial seizures that are apparent to an observer). Patients aged 12 years and older with suspected MTLE will be candidates for recruitment if disabling seizures: 1) have not responded to two or more antiepileptic drugs, one of which must be either Dilantin, Tegretol, or Carbatrol, and 2) have not persisted, according to defined criteria, for more than two years. Fifteen epilepsy surgery centers spaced evenly across the country will actively recruit patients meeting these criteria. These patients will undergo a rigid presurgical evaluation protocol, standardized across centers, and 200 surgical candidates will then be randomized to either anteromesial temporal resection or two years of additional pharmacotherapy. Studies will test five hypotheses: 1) Surgical treatment will be more effective than medical treatment in reducingthe frequency and severity of epileptic seizures; 2) Surgical treatment will be more effective than medical treatment in improving quality of life; 3) Surgical treatment will be more effective than medical treatment in improving psychological and social function; 4) Morbidity and mortality associated with surgical treatment will be no greater than that associated with medical treatment; and 5) Progressive hippocampal atrophy and mesial temporal hypometabolism will occur only in patients who continue to have frequent complex partial and generalized tonic-clonic seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS042372-04
Application #
7161703
Study Section
Special Emphasis Panel (ZNS1-SRB-K (01))
Program Officer
Hirtz, Deborah G
Project Start
2002-09-01
Project End
2010-11-30
Budget Start
2006-12-01
Budget End
2010-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$497,671
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Engel Jr, Jerome (2018) Epileptogenesis, traumatic brain injury, and biomarkers. Neurobiol Dis :
Vakharia, Vejay N; Duncan, John S; Witt, Juri-Alexander et al. (2018) Getting the best outcomes from epilepsy surgery. Ann Neurol 83:676-690
Engel Jr, Jerome; Bragin, Anatol; Staba, Richard (2018) Nonictal EEG biomarkers for diagnosis and treatment. Epilepsia Open 3:120-126
Engel Jr, Jerome (2018) The current place of epilepsy surgery. Curr Opin Neurol 31:192-197
Jozwiak, Sergiusz; Becker, Albert; Cepeda, Carlos et al. (2017) WONOEP appraisal: Development of epilepsy biomarkers-What we can learn from our patients? Epilepsia 58:951-961
Dewar, Sandra; Eliashiv, Dawn; Walshaw, Patricia D et al. (2016) Safety, efficacy, and life satisfaction following epilepsy surgery in patients aged 60 years and older. J Neurosurg 124:945-51
Jobst, Barbara C; Engel Jr, Jerome (2015) Is it time to replace epileptic spikes with fast ripples? Neurology 85:114-5
Chiang, Sharon; Stern, John M; Engel Jr, Jerome et al. (2015) Structural-functional coupling changes in temporal lobe epilepsy. Brain Res 1616:45-57
Haneef, Zulfi; Chiang, Sharon; Yeh, Hsiang J et al. (2015) Functional connectivity homogeneity correlates with duration of temporal lobe epilepsy. Epilepsy Behav 46:227-33
Pitkänen, Asla; Engel Jr, Jerome (2014) Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics 11:231-41

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