Susan S. Spencer - US grants

This is a Shannon Award providing partial support for research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. Further scientific data for the CRISP System are unavailable at this time.

Approximately 1-2% of the United States population has epilepsy. Most epilepsy is well-controlled with the available anticonvulsant agents. Approximately 20% (250,000 in the United States), however, have medically refractory (i.e. intractable) epilepsy. While surgical treatment of intractable epilepsy has been gaining in acceptance and use, comprehensive assessments of outcomes are lacking. As pointed out during the NIH Consensus Development Conference on Epilepsy Surgery, there is a fundamental lack of reliable information concerning the effects of surgery, not just on seizure control but on quality of life, and specifically whether seizure control is accompanied by improvements in quality of life. To make rational recommendations and decisions regarding the use of epilepsy surgery, one needs definitive and comprehensive information regarding the risks and benefits of surgery. The following proposal is for a unique, prospective, multi-center, longitudinal study of approximately 400 patients who will undergo resective surgery for relief of medically intractable seizures. To accrue an adequate sample size, patients will be recruited from six centers in the Northeast. Patients will be prospectively recruited and followed from the beginning of the presurgical evaluation to at least two years after surgery. The primary goals of the study are 1) to determine the probability and predictors of entering a one-year remission (i.e. no seizures for one year) within two years after surgery; 2) to determine the magnitude of change from presurgical baseline in quality of life and in productive activity at 3 months, 1 year and two years after surgery, and to determine how much change can be expected as a function of change in seizure frequency, seizure severity, and decrease in medications; 3) to determine the magnitude and nature of changes in cognitive function post- versus presurgery; and 4) to document psychiatric and neurologic complications. We also propose to conduct methodologic work on health-related quality (HRQOL) assessment for epilepsy surgery, using data that will be collected already for the primary study goals. These analyses include refinement of a recently developed seizure-based outcome system so that its outcome categories maximally reflect HRQOL after epilepsy surgery, comparison of the measurement properties of three HRQOL measures (SF-36, ESI-55, and QOLIE- 89) In study patients, and development and evaluation of Spanish language versions of these HRQOL measures. The proposed study represents a unique, multi-center effort that will result in the largest systematic study of epilepsy surgery to date and will provide definitive answers to key questions regarding the outcomes of epilepsy surgery, as well as their measurement.

DESCRIPTION (Applicant's Abstract): Nearly one percent of the United States population has epilepsy. By some estimates more than 20% of those patients are inadequately treated despite a growing number of anti-epileptic medications. Resective surgery is increasingly used to treat this population, despite its high costs. Outcome with regard to seizures following epilepsy surgery has rarely been systematically or prospectively assessed in large samples, and quality-of-life, cognitive, neurologic, and psychiatric status following epilepsy surgery in the long or short-term are largely unexplored. Over the past 5 years we enrolled a 400 patient cohort in the first multi-center study of epilepsy surgery. Evaluation and treatment of these patients incorporated uniformity and technological advances, as well as reliable and validated baseline and follow-up measures of psychiatric status, cognitive function, quality-of-life, seizure severity and frequency, productive activities, and family dynamic. We propose to complete two-year follow-up on the full cohort, and extend follow-up to 5 years. We seek to define the occurrence and predictors of seizure remission, as well as improvements in quality-of-life, and stability or improvement in psychiatric, cognitive and neurologic status, based on factors in the preoperative profile and postoperative observations. We also propose to define relapse and continued remission off all medications and the predictors for successful medications withdrawal, an important yet unstudied aspect of epilepsy surgery. Our primary goals are: 1. to study the probability of achieving 1, 2, and 5 year seizure remission after epilepsy surgery, and the probability of relapse after remission over a total 5 year follow-up, as well as the prognostic significance of specified preoperative and postoperative factors; 2. to determine the probability of relapse and prediction of relapse in patients who discontinue medications after 2 year remission, and prognostic factors for successful outcome; 3. to assess self reported quality-of-life and employment status yearly for 5 years after resective epilepsy surgery, and to determine the magnitude and time course of change, and the extent to which seizure response and medication changes are associated with alterations in self-perceived health and employment; 4. to identify the nature and magnitude of changes in cognitive and neurologic status after resective epilepsy surgery, the factors that predict changes, and their resilience and functional impact over 5 years of follow-up; and 5. to prospectively assess changes in behavior and psychiatric profile yearly for 5 years and examine predictive factors in long-term prognosis of depression, anxiety and other psychiatric diagnoses, as well as family dynamics. The proposed study represents a unique multi-center effort that will result in the largest systematic study of epilepsy surgery to date, and will provide definitive answers to key questions regarding the outcomes of epilepsy surgery, their measurement, and their prediction in a contemporary patient population.

[unreadable] DESCRIPTION (provided by applicant): Previous work in seizure prediction can be categorized, broadly, into three phases. A conceptual breakthrough was achieved in the first phase through the definition of the problem and initial attempts to predict the onset of seizures. Work in the second phase was fueled by a signal theoretical breakthrough, the description of chaos in deterministic systems, and both conceptual and theoretical progress are evident in this work. We argue that a third phase of work in this field has begun more recently. We believe this phase will be characterized by both technical advances that allow the acquisition and analyses of comprehensive data sets and the application of a wider range of analysis methods. We wish to strengthen this third phase of work by bringing a comprehensive knowledge of epilepsy, a non-prejudiced application of powerful linear and nonlinear methods, and a strong theoretical backing for these methods to bear on the problem of seizure prediction. Specifically, we concur with the suggestion that the central role of synchrony in seizure generation would suggest value for measures of synchrony and seek to test signals from multiple locations for nodal, pathway, and central disruptions in the period leading to seizures. The proposed study is composed of retrospective studies to detect changes in network locations in patients with: (1) medial temporal lobe epilepsy, and (2) superior parietal-medial frontal onset, and (3) occipital-temporal onset of seizures, and prospective studies to evaluate the specificity of these changes and their utility for both offline and real-time prediction of seizures. Fifteen patients will be studied in the retrospective studies, and 45 patients will be studied in the prospective studies. [unreadable] [unreadable]