Authors :
Presenting Author: Hal Blumenfeld, MD PhD – Yale University
Taruna Yadav, PhD – Yale University; Zheng Zhang, PhD – Yale University; Vaclav Kremen, PhD – Mayo Clinic; Kristine DaCosta, NA – Yale University; Maxime Oriol, NA – Yale University; Christopher Benjamin, PhD – Yale University; Kate Christison-Lagay, PhD – Yale University; Eyiyemisi Damisah, MD – Yale University; Allyson Derry, NA – Yale University; Abhijeet Gummadavelli, MD PhD – Yale University; Tyler Hamilton, NA – Yale University; Lawrence Hirsch, MD – Yale University; Patrice Lauture, NA – Yale University; Bogdan Litvinov, MD – Yale University; Dennis Spencer, MD – Yale University; Kimberly Bailey, NA – Mayo Clinic; Karla Crockett, NA – Mayo Clinic; Starr Guzman, NA – Mayo Clinic; Vladimir Sladky, MSc – Mayo Clinic; Delana Weis, NA – Mayo Clinic; Jennifer Hong, MD – Dartmouth-Hitchcock Medical Center; Krzystof Bujarski, NA – Dartmouth-Hitchcock Medical Center; Charlotte Jeffreys, NA – Dartmouth-Hitchcock Medical Center; Anastasia Kanishcheva, NA – Dartmouth-Hitchcock Medical Center; Grant Moncrief, NA – Dartmouth-Hitchcock Medical Center; Robert Roth, NA – Dartmouth-Hitchcock Medical Center; George Thomas, MD – Dartmouth-Hitchcock Medical Center; Jonathan Baker, PhD – Weill Cornell Medical School; Eun Young Choi, PhD – Stanford University Medical Center; Jaimie Henderson, MD – Stanford University Medical Center; Matthew Hook, NA – University of Florida; Irina Korytov, NA – University of Florida; Kyle O’Sullivan, PhD – University of Utah; Brian Rutt, PhD – Stanford University Medical Center; Joseph Giacino, PhD – Harvard Medical School; Benjamin Brinkmann, PhD – Mayo Clinic; George Culler, MD – Dartmouth-Hitchcock Medical Center; Nicholas Gregg, MD – Mayo Clinic; Brian Lundstrom, MD PhD – Mayo Clinic; Imran Quraishi, MD – Yale University; Joshua Aronson, MD – Dartmouth-Hitchcock Medical Center; Jason Gerrard, MD PhD – Yale University; Jamie Van Gompel, MD – Mayo Clinic; Christopher Butson, PhD – University of Florida; Nicholas Schiff, MD – Weill Cornell Medical School; Barbara Jobst, MD PhD – Dartmouth-Hitchcock Medical Center; Gregory Worrell, MD PhD – Mayo Clinic
Rationale:
Impaired conscious awareness has a major negative impact on quality of life for people with temporal lobe epilepsy (TLE). The START clinical trial investigates the feasibility and safety of intralaminar thalamic centrolateral nucleus (CL) stimulation to restore consciousness in patients with medically refractory temporal lobe epilepsy.Methods:
Five patients with TLE were implanted with the investigational Medtronic Summit RC+STM neurostimulator. Following recovery, CL stimulation was individually titrated to tolerated levels in the waking state. Effectiveness of bilateral CL stimulation was initially evaluated without seizures during sleep, based on electrophysiological arousal from slow-wave sleep and video behavior. Patients subsequently entered a randomized double-blind phase, where all seizures received therapeutic responsive hippocampal stimulation, but thalamic CL stimulation was randomized from seizure to seizure as therapeutic or sham. Behavior was scored (0- 3) at baseline and during seizures using the Automatic Response Testing in Epilepsy (ARTiE) Watch. Patients also completed an electronic seizure self-report diary.Results:
During sleep titration, all five patients exhibited scalp EEG and behavioral changes consistent with arousal, including a decrease in delta/theta (1-7 Hz) band power during stimulation. In two of five patients, robust arousal state change was characterized by eye-opening and natural spontaneous movements along with transition from N2/3 sleep to waking state on EEG. All patients returned to sleep after the stimulation was turned off. Average behavioral scores during seizures (2.19) were significantly lower than baseline (2.97; p < .05, Wilcoxon rank sum test). Among the two patients who have exited the blinded CL phase, one patient scored significantly higher on responsiveness and memory tests during seizures with therapeutic CL stimulation (n= 16 seizures) compared to sham (n= 12 seizures). Of 197 seizures, the five patients reported impaired awareness in 52%; impaired recall of events in 62%; and impaired ability to respond in 55%.