Seizure-Triggered Vagus Nerve Stimulation Using Patient-Specific Seizure Onset Detection

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1 Seizure-Triggered Vagus Nerve Stimulation Using Patient-Specific Seizure Onset Detection Ali Shoeb, Alaa Kharbouch, John Guttag Massachusetts Institute of Technology, Cambridge, MA, USA Trudy Pang, Steven Schachter Beth Israel Deaconess Medical Center, Boston, MA, USA International Workshop on Seizure Prediction June 6 th 2009 Contact: Ali Shoeb (ashoeb@mit.edu)

Vagus Nerve Stimulation Automatic Mode VNS: Repeated stimulation of the left vagus can reduce the average number/severity of seizures experienced over time 1.

2 Vagus Nerve Stimulation Automatic Mode VNS: Repeated stimulation of the left vagus can reduce the average number/severity of seizures experienced over time 1. On-demand Mode VNS: Stimulation of the left vagus nerve immediately after seizure has been reported to abort or reduce the intensity and duration of a seizure 2-4. ~70% of VNS patients use on-demand VNS report: 20% report experience seizure termination 30% report experience seizure attenuation 50% report experience no effect [1] VNS Study Group Neurology 1995 Feb; 45(2): [2] Morris et. al Epilepsy Behav 2003;4:740-5 [3] Boon et al. J Clin Neurophysiol Sept; 18(5): [4] Hammond et al. Epilepsia 31(Suppl. 2): S51-S59, 1990.

3 Study Protocol Study Population Adults (> 18 years old) Long-term users of VNS ( > 1 year ) 2-3 seizures a week Study Protocol Admitted to hospital for 6 days. No changes to AEDs or VNS settings. Continuous Video, EEG, ECG, VNS signals recorded 1 baseline seizure and 24 hours of non-seizure EEG used for training Subsequent seizures are detected and engaged by system Assessment Compare baseline and engaged seizures Examine Ictal and Post-ictal periods. Look for electrographic or behavioral change

4 Seizure Detection and VNS Activation System Computerized System VNS Patient EEG and ECG Acquisition EEG-ECG Based Seizure Detection Vagus Nerve Stimulator Electromagnet

5 Seizure Detection and VNS Activation System EEG Cap Electromagnet Vest Electromagnet Switch Box EEG/ECG Recorder Battery Seizure Detector Computer

6 EEG-Based Patient-Specific Seizure Detection EEG Ch 1 EEG Ch 2 EEG Ch Hours of Scalp EEG from 16 Pediatric Patients 93% Sensitivity 1 False Detections every 5 hours 6.8 +/- 2 seconds Detection Latency 1,1 1,2 1,8 2,1 2,2 2,8 18,1 18,2 18,8 Test Feature Vector Training Seizure Feature Vectors Training Non-Seizure Feature Vectors Classification: 2-Class Support Vector Machine [1] Shoeb et al. Epilepsy Behav 2004 [2] Shoeb et al. EMBS Conf. 2007

7 Case #1: Complex Partial Seizures Patient A is a 39-year-old woman with a long history of refractory complex partial seizures. Patient A s seizures last for 1-2 minutes and consist of repeatedly asking questions and blank stares. Patient A does not use magnet-mode VNS.

8 Baseline, Training Seizure

9 EEG-based Detection and VNS Activation

10 Why Was There No Effect? Seizure detection was too late? VNS stimulation parameters not optimally set? Patient not a responder to on-demand VNS?

11 Seizure-Associated Tachycardia Eye Flutter HR Acceleration Theta Waves

12 Seizure-Associated Tachycardia Temporal Theta Waves

13 EEG/ECG-Based Patient-Specific Seizure Detection EEG Ch 1 EEG Ch 2 EEG Ch 16 ECG Mean Heart Rate 1,1 1,2 1,8 2,1 2,2 2,8 18,1 18,2 18,8 ECG Accumulated Heart Rate Change ECG, 2,1 Test Feature Vector Training Seizure Feature Vectors Training Non-Seizure Feature Vectors Classification: 2-Class Support Vector Machine N i 1 ( HR[ i] HR[ i 1])

14 EEG/ECG-based Detection and VNS Activation Seizure Detected VNS Active

15 Stereotypical Seizure-Associated Tachycardia Training Seizure Test Seizure

16 False Detections

17 False Detections

18 Performance Summary 81 hour Test 1 False Detection every 2.5 hrs 5/5 Seizures Detected Latency: Relative To Theta Waves: 1.5 seconds Relative To ECG Acceleration: ~ 8 seconds

19 Case #2: Secondarily Generalized Seizures Patient B is a 41-year-old woman with a long history of secondarily generalized seizures. Patient B s secondarily generalized seizures consist of a 1 minute long tonic-clonic phase, and 30 minute post-ictal phase. According to patient B s caregiver, initiating VNS early in the ictal phase results in reduced anxiety and confusion during the post-ictal phase.

20 Baseline, Training Seizure

21 EEG-based Detection and VNS Activation Seizure Detected

22 EEG-based Detection and VNS Activation

23 Impact of Seizure-Triggered VNS Electrographic Training seizure Tonic-clonic phase: 55 seconds Post-ictal phase: 29 minutes Testing Seizure Tonic-clonic phase:65 seconds Post-ictal phase: 30 minutes Behaviorally, relative to the first seizure, patient B became oriented to her surroundings 10 minutes sooner following the end of the tonic-clonic phase of the second seizure. She was also significantly less anxious.

24 Performance Summary 24 hour test 0 False Detections 1/1 Seizures Detected Latency Poor. Due to small training set

25 Case #3: Tonic Seizures Patient C is 24 year old male with Lennox- Gastaut syndrome. Patient C suffers from daily episodes of tonic, atonic, or mycolonic seizures. Patient C does not use magnet-mode VNS.

26 Baseline, Training Seizure

27 EEG-based Detection and VNS Activation Seizure Detected

28 EEG-based Detection and VNS Activation

29 Conclusion Seizure Detection Detection of seizure onset using scalp EEG can be used to trigger on-demand VNS Fusion of EEG and ECG information can enhance seizure onset detection performance Neurostimulation More patients need to be enrolled in study before we can draw conclusions on impact of on-demand VNS.

Epilepsy: diagnosis and treatment. Sergiusz Jóźwiak Klinika Neurologii Dziecięcej WUM

Epilepsy: diagnosis and treatment Sergiusz Jóźwiak Klinika Neurologii Dziecięcej WUM Definition: the clinical manifestation of an excessive excitation of a population of cortical neurons Neurotransmitters: