TY - JOUR
T1 - An introduction to contingent (closed-loop) brain electrical stimulation for seizure blockage, to ultra-short-term clinical trials, and to multidimensional statistical analysis of therapeutic efficacy
AU - Osorio, I.
AU - Frei, M. G.
AU - Manly, B. F.J.
AU - Sunderam, S.
AU - Bhavaraju, N. C.
AU - Wilkinson, S. B.
PY - 2001
Y1 - 2001
N2 - Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.
AB - Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.
KW - Closed-loop
KW - Detection
KW - Seizure blockage
KW - Ultra-Short-term
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U2 - 10.1097/00004691-200111000-00003
DO - 10.1097/00004691-200111000-00003
M3 - Article
C2 - 11779966
AN - SCOPUS:0035664172
SN - 0736-0258
VL - 18
SP - 533
EP - 544
JO - Journal of Clinical Neurophysiology
JF - Journal of Clinical Neurophysiology
IS - 6
ER -