1. VNS Therapy ™ System for Epilepsy Patients VNSSS 05-11-1000-EC Wei Gong Memorial Hospital NOV15 2007 AST A Light on the Horizon
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3. Easy to Control Group 1st line AED: CAM, DIZ, DIL etc 2nd line AED: Top, Neuro, Oxb etc Seizure free with or without side effect Well management: 3-month prescription Tolerant side effect Controlled Seizure or free of seizure Satisfied and Happy Patient
4. Difficult to Control Group 1st line & 2nd line AED failure Multi-AED or Treatment-Resistant Seizure, and AED side effect Continue Multi-AED with side effect Surgical evaluation Search for alternative treatment Suffer from bad QoL Unhappy patients
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6. What are patients looking for? B QoL SE Difficult to Control Group Value B QoL SE Easy to Control Group Value
7. Do we have other tools? Product Side Effect CNS Vision Skin GU/ Reproduction Liver toxicity Others Carbamazepine v V (Diplopia) V, S-J Valporic Acid / Sodium v V, POD V B.W. Phenytoin v V Gum hyperplasia Lamotrigine V Rush, S-J (A: 1/1000, C: 1/50~1/100) Vigabatrin V Vision angle narrow B.W. Gabapentin V Topiramate V Glaucoma (23/82,500) Kidney stone (1.5%) B.W. VNS X X X X X x
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11. Vagus Nerve Projects to Key Brainstem Regions III- Henry TR. Neurology. 2002;59(suppl 4):S3-S14. STN=spinal trigeminal nucleus; NTS=nucleus tractus solitarius; DMN=dorsal motor nucleus of the vagus; AP=area postrema; NA=nucleus ambiguus; CN-X=cranial nerve X; RF=reticular formation. Bilateral projections on nucleus tractus solitarius (NTS)
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14. VNS on Human EEG Year Investigator Patients Result 1992 Hammond Partial epilepsy (n=9) VNS T herapy aborted Adults seizures (n=2) early in epileptic event 1993 Salinsky, Partial epilepsy (n=6) No statistically significant Burcheil Adults effects on EEG 2001 Olejniczak Presurgical evaluation VNS T herapy decreased (n=1) hippocampal spikes at Adults 30 Hz; increased at 5 Hz 2001 Koo Generali s ed and partial Generali s ed and focal onset seizures; high frequency spikes diminished during of interictal discharges; VNS T herapy (12 months) younger patients Henry TR. Neurology. 2002;59(suppl 4):S3-S14.
15. Serial EEGs of the same patient. Above: baseline EEG showing active multifocal independent epileptiform activity. Koo B. EEG changes with vagus nerve stimulation. J Clin Neurophysiol ; 18 (5): 434-441.
16. EEG 3 months after the patient received a VNS implant showing similar alternating paroxysms of spikes/spike and wave activity with periods of spike-free intervals during the time when stimulation is off. Koo B. EEG changes with vagus nerve stimulation. J Clin Neurophysiol ; 18 (5): 434-441.
17. EEG at 1 year showing further prolongation of intervals of spike-free period. Koo B. EEG changes with vagus nerve stimulation. J Clin Neurophysiol ; 18 (5): 434-441.
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23. Responder Rate of VNS On Average, 49% of the patients are responders to VNS Therapy Total Patient number: 4432, 50% seizure reduction responder: 2172
39. VNS referring center in Taiwan North Taiwan: CGMH VGH Cathy GH Central Taiwan: CMMH VGH-TC CHCH South Taiwan: CKUH CGMH-KS VGH-KS East Taiwan: Tzu-Chi
40. PATIENT SATISFACTION Testimonial Heather, 21 years of age VNS Therapy since 1992 I was sluggish and tired, had very few friends, and no social life. The only options were to add another medication or to increase the medications. “ ” Heather before VNS Therapy « Since VNS Therapy, my whole life has been completely changed. I graduated from high school. I have made friends and am able to have a normal life. I have a job that I love in a day care centre. The magnet stops the seizures and also decreases the length of the seizures. Not only do I have a new life but I feel great! »
83. On-going Research on VNS Disease Author Subjects Key Finding Depression Rush et al 30 patients Depression improvement Sackeim et al 60 patients Depression improvement, smaller, response predictors Sackeim et al Patients No adverse cognitive effects of VNS over time Marangell et al 30 Patients Continued improvement at 1 year Rush et al 240 Patients Ongoing Krahl et al Rats Antidepressant effects is Porsolt Swim Test Anxiety Group 8 Patients Ongoing Obesity Roslin et al 10 dogs Weight reduction in chronic model Roslin et al Patients Ongoing Alzheimer’s dz 10 Patients Initial results promising Migraine Ongoing
94. Pulse Generator: Physical Characteristics Model 102 Model 102R Model 101 Titanium Case 6.9 mm 52.2 mm 51.6 mm 6.9 mm 52.2 mm 51.6 mm 10.3 mm 54 mm 54 mm Weight 25 grams 27 grams 38 grams Header Polyurethane Polyurethane Epoxy Power Source Lithium Carbon Monofluoride Battery Lithium Carbon Monofluoride Battery Lithium Carbon Monofluoride Battery Longevity 6 - 11 years depending on stimulation parameters 6 - 11 years depending on stimulation parameters 8 - 12 years depending on stimulation parameters Cavity Single Dual Dual Serial #’s < 1,000,000 1,000,000 > 0
108. Program Setting: Physicians Experiences Duty cycle=(ON+4)/(ON+OFF) in sec Some physicians use the following progression to find the optimal duty cycles for their patients ON (sec) OFF (min) Duty Cycle (%) 30 5 10 30 3 16 30 1.8 25 30 1.1 35 21 0.8 36 14 0.4 41
109. ERDMC between 3 TRT of Refractory Epilepsy Parameters Before (range) After (range) Conservatively treated patients Cost HAD 875 (0-8494) 870 (0-6310) Cost clinic visit 114(39-243) 93(22-132) Cost AEDs 1305(44-6299) 1218(110-2885) Cost lab test 230(110-386) 241(110-441) ERDMC 2525(287-15254) 2421(387-7409) CPS(#/mo) 12(1-30) 9(0-30) Surgically treated patients Cost HAD 33(0-3398) 222(0-5339) Cost clinic visit 128(66-154) 66(22-110) Cost AEDs 986(84-2568) 881(90-3242) Cost lab test 18(11-33) 18(11-33) ERDMC 1465(205-5138) 1186(149-6393) CPS(#/mo) 17(0-210) 2.3(0-53) VNS-treated patients Cost HAD 3048(0-14561) 693(0-3155) Cost clinic visit 146(132-265) 89(6-132) Cost AEDs 1389(278-2307) 1498(416-2925) Cost lab test 243(0-331) 216(0-331) ERDMC 4826(631-16661) 2496(813-5432) CPS(#/mo) 21(2-180) 9.3(0-60)
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118. Program Settings: New Parameter Study Results *The data is similar to those found in the prior study to let FDA approval: 11% ( 75%) in 30 sec ON and 5 min OFF If the patients has shown no response after several months, then decreasing the OFF times may be appropriate Data on file. Cyberonics, Inc. Houston, TX Group ON (sec) OFF (sec) DC (%) N 75% responder A 7 18 28% 19 5% B 30 30 50% 19 0% C* 30 180 14% 23 13%
125. Heather, 21 years of age VNS Therapy since 1992 Since VNS Therapy, my whole life has been completely changed. I graduated from high school. I have made friends and am able to have a normal life. I have a job that I love in a day care centre. The magnet stops the seizures and also decreases the length of the seizures. Not only do I have a new life but I feel great! “ ”
126. Prevent Seizure Here is what some patients are saying: Before the VNS, I had so many seizures, I felt like a prisoner in my own home. Thankfully things are much better now. “ ” When I got the VNS implant, it changed my whole life. “ ” The longer we go, the better it gets. “ ” VNS Therapy brings seizure relief to many patients
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128. Can improve the quality of every day life Jerry, 44 years of age “ ” Since the implant, I have been able to live a normal life free from the side effects of medication... My life has regained a semblance of normality.
129. Kristen, 19 years of age VNS Therapy since 1997 I was nervous about the idea of having surgery when I first heard about VNS Therapy. But if I had known then how much better my life would be, I wouldn’t have waited so long to get it. And as it turned out, the surgery was not a big deal. I was back home in a couple of hours. “ ”
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132. Benefit of Early VNS Treatment – Quality of Life P=0.003 P< 0.002 Ref: J.Ben Renfroe and James W.Wheless Neurology 59 (4), S26-S30, 2002
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