Vns Therapy™ System For Weikong For Print
Upcoming SlideShare
Loading in...5
×
 

Vns Therapy™ System For Weikong For Print

on

  • 3,293 views

 

Statistics

Views

Total Views
3,293
Views on SlideShare
3,286
Embed Views
7

Actions

Likes
0
Downloads
30
Comments
0

1 Embed 7

http://www.slideshare.net 7

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Vns Therapy™ System For Weikong For Print Vns Therapy™ System For Weikong For Print Presentation Transcript

  • VNS Therapy ™ System for Epilepsy Patients VNSSS 05-11-1000-EC Wei Gong Memorial Hospital NOV15 2007 AST A Light on the Horizon
  • The Epilepsy Patients
    • Easy to Control:
      • 47% can be controlled by 1 AED
      • Only 17% can be controlled by added-on AED
    • Difficult to Control:
      • 39% of Total Epilepsy
  • 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
  • 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
  • What are patient looking for?
    • Quality of Life Improvement
    II Treatment’s Benefit – Treatment’s Side effect
  • What are patients looking for? B QoL SE Difficult to Control Group Value B QoL SE Easy to Control Group Value
  • 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
  • Seizure reduction: VNS + AED Medium (mean) seizure reduction in adults patients Add-on therapy for partial refractory epilepsy
    • Ref: J.A. French et al. Neurology 2004, 62: 1261-1273, Welinaton A et.al, CNS Drugs 2001: 15(2):137-163;
    • Gil-Nagel Rev Neurol 2005. 40(10):609-613; G Zaccara et al. Acta Neurol Scand 2006; 114:15-168;
    • T.A. Glauser Epilepsia 1999; 40 (Suppl.5) S71-S80; P. Genton et al. Acta Neurol Scan 2006; 113:387-394
  • Too Good to be True?
    • Unique Mechanism of Action
  • Mechanism of Action
    • VNS works by triggering the left Vagus to send electrical pulses into the brain
      • The Vagus is projected througth the NTS, Locus coeruleus, Raphe magnus nuclei, Limbic structure, Hypothalamus and Thalamus.
    • These neuro pathway are important for VNS’s positive effects.
  • 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)
  • Vagus Nerve and NTS Project to Key Brainstem Regions III- Henry TR. Neurology. 2002;59(suppl 4):S3-S14. KFN=K ö lliker-Fuse nucleus; LC=locus coeruleus; ICH=inferior cerebellar hemisphere; RMN=raphe magnus nucleus; PBN=parabrachial nucleus; NTS=nucleus tractus solitarius.
    • Parabrachial nucleus of pons has widespread cerebral projections
    • Locus coeruleus supplies norepinephrine
    • Raphe magnus nuclei supply serotonin
  • Vagus Nerve - NTS - PBN Project to Key Cerebral Regions
    • Limbic structures
      • Amygdala
      • Insula
    • Autonomic structures
      • Hypothalamus
      • Periaqueductal gray
    • Reticular structures
      • Thalamus
    III- Henry TR. Neurology. 2002;59(suppl 4):S3-S14. NTS=nucleus of the tractus solitarius; PBN=parabrachial nucleus; PAG=periaqueductal gray; CNA=central nucleus amygdala; PVN=periventricular nucleus of hypothalamus; VPM=ventral posterormedial nucleus of thalamus.
  • 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.
  • 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.
  • 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.
  • 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.
  • MOA Comparison
    • AED
      • Neurotransmitter inhibitor
      • Suppress both, epileptic and normal brain function
    • Cranial Surgery
      • Removal of epileptic region of brain
    • VNS
      • Does NOT suppress nor remove brain function
  • Not Only Seizure Control
    • “ Quality of Life of can not be maximized if we solely focus on seizure frequency and severity ”
    • Schachter, 26 th international epilepsy congress
  • VNS Therapy  Quality of Life Benefits
    • VNS Patient Registry: January 25, 2002
    • Data on file, Cyberonics, Inc.
    % of Registry Patients Better or Much Better * Constant Cohort Data * Fewer than 7% of patients reported any single measure worse
  • 15 children study on cognition, QoL, behaviour and mood
    • N=15, Mean Age=11 (4-17)
    • Seizure Reduction:
      • 6/ 15 children showed a 50% or more reduction in seizure frequency;
      • 1/15 became seizure-free.
      • 2/15 children had a 25—50% seizure reduction. .
    • QOL, Mood, Cognition
      • 13/15 children there was an improvement in NHS3 (National Hospital Seizure Severity Scale)
      • There were no changes in cognitive functioning.
      • 12 showed an improvement in QOL.
      • 11 improved in seizure severity and mood and 5 also in depressive parameters.
    • Conclusion: This study has shown a good anti-seizure effect of VNS, an improvement in seizure severity and in QOL and a tendency to improvement over time.
    Tove Hallbo¨o¨k et.al , Seizure (2005) 14, 504—513
  • QoL Improvement
    • In addition to experiencing fewer and less severe seizures, many VNS Therapy  patients and their doctors also report:
      • Improvements in their mood
      • Increased alertness
      • Improved memory
      • Possible reduction in number and doses of medications
      • Fewer visits to the emergency room
    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.
  • Responder Rate of VNS On Average, 49% of the patients are responders to VNS Therapy Total Patient number: 4432,  50% seizure reduction responder: 2172
  • Seizure Free Rate Total patients: 7174, Seizure free: 533, Seizure free rate: 7.4%
  • Reduction by Seizure type
    • Lennox-Gastaut Syndrome: 58% reduction after 6 months
    • LGS + Drop Attacks: 88% reduction after 6 months
    • LGS + Absence: 81% reduction after 6 months
    • Frost M. Epilepsia.2001;42(9)1148-1152.
    • Tuberous Sclerosis: 50 % reduction in 90% patients
    • Parain D. Paediatric Neurology. 2001;25(3):213-216.
  • Seizure Reduction by Age Group - Wheless V d - 47% 50% 53% 50% 50% 56% 56% 61% 61% 59% 0 10 20 30 40 50 60 70 (0-6) (7-11) (12-18) (19-35) (36-55) 3 months 12 months Wheless J et al. Neurology. 2002;59 (Suppl 4) S21-S25. 115/229 57/96 215/433 136/222 323/610 198/326 543/1080 349/626 477/1014 318/558 Patients (%) Patients with ≥50% Reduction in Seizures Age (Years) VNS is more effective in patients under 18
  • SAFETY Surgical Complications 1 Bruce DA, et al. Epilepsia. 1998;39(suppl 6):92-93. Epilepsy Clinical Studies (n=454)
    • Surgical Complication  0.5% 1
      • Infection without explant 1
      • Infection with explant 1
      • Hoarseness/temporary vocal cord paralysis 1
      • Hypoesthesia/lower left facial paresis 1
    1.8% 1.1% 0.7% 0.7%
    • Mortality
    0.0%
  • SAFETY Side Effects
    • Hoarseness,
    • Paresthesia,
    • Shortness of breath,
    • Dry cough.
      • decrease with time
      • only when stimulation is ON. (30sec/5min)
      • can be turned off by patient
  • Timing for VNS Therapy
    • Difficult to treat Epilepsy
    • Patient not suitable or resists cranial surgery
    • Patient suffers from poor Quality-of-Life
    • Patient suffers from mental depression, poor memory and alertness.
    • Possible drug reduction and to reduce drug side effects
  •  
  •  
  • VNS Case Manager Hotline Medical / Financial Evaluation Device Implantation (Case Manager assist) Monthly Followup (Case Manger assist)
  • PATIENT SATISFACTION
    • Over 70% of patients chose to get new VNS after old battery expired.
    • Ben-Menachen & French, 26 th international epilepsy congress
  • PATIENT SATISFACTION VNS v.s. AEDs
    •  Continuation rates at 3 years:
      • VNS: 72%
      • Levetiracetam: 37%
      • Topiramate: 30%
      • Lamotrigine: 29%
    • VNS Therapy are remarkably better than long-term continuation rates with other treatments for pharmacoresistant epilepsy
  • World Wide Experience
      • Now, over 50,000 patients have been treated with VNS Therapy within 75 countries
  • What VNS can bring to your patients:
    • Better QoL:
      • Mood improvement
      • Alertness increase
      • Memory increase
    • Better Efficacy to AED but much less side effects
    • 7.4% Seizure free rate
  • Thank you for your attention Q&A
  • What are patient looking for?
    • Mental health
    • Physical function
    • Physical role limitation
    • Emotional role limitation
    • General health
    • Social function
    • Vitality
    • Bodily pain
    0.01 0.1 1 10 100 More important to More important Clinicians to patients Odds Ratios (95% CI) Ref: P.M. Rothwell et.al BMJ 1997; 314:1580
  • 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
  • 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! »
  • DESCRIPTION
    • Proven Treatment for Epilepsy
    • Improves Quality-of-Life
    • Implantable stimulator delivers 24/7 therapy
    • Few Side-Effects
  • Mechanism of Action
  • World Wide Experience I
    • 1985 First animal studies (J. Zabara, Temple University)
    • 1988 First human implant (K. Penry, B.J. Wilder, E. Ramsay)
    • 1994 European community approval for RE (CE Mark)
    • 1997 US FDA commercial approval for RE
    • 2002 15,000+ patients treated worldwide
    • 2004 25,000+ patients treated
    • 2005 FDA approval for treatment in Resistant Depression
  • Patient Assistance Program
    • VNS Easy Access Program
      • Rental Program
      • Monthly payment + initial setting cost
    • VNS Case Manager helps with
      • Patients Education
      • Program Setting
      • Trouble Shooting
  • SURGICAL PROCEDURE
  • Pre-Implant: Summary
    • Power up the fully charged computer previously loaded with Programming Software
    • Attach Programming Wand (with working 9V battery) to computer
    • Pre-op I.V. antibiotic administration
    • Use computer and wand to perform generator “Communication Check” outside of sterile field in sterile package by performing an “Interrogation”
    • Program in patient initials and implant date
  • VNS System Implant: Positioning the Patient
    • Anesthesia administered
    • Patient in supine position with head turned to the right
  • VNS System Implant: Marking the Incision Sites
    • Transverse incision site on left neck marked, in skin crease midway between clavicle and mastoid process, for electrode placement (for thick neck, vertical incision used). Transverse incision performed to “hide” scar in neck.
    • Incision site marked at front fold of left axilla or on left frontal chest wall aligned to the center of clavicle for generator placement
    Clavicle Anterior fold of axilla incision site option Neck incision site
  • VNS System Implant: Platysma Divided
  • VNS System Implant: Palpating the Carotid Pulse
  • VNS System Implant: The Exposed Carotid Sheath
  • VNS System Implant: Isolating the Vagus Nerve
    • Expose > 3cm of nerve.
    • Use soft vessel loops to gently lift nerve.
    • Avoid excessive handling of nerve to prevent injury & preserve branches off the vagus.
    • Avoid letting the nerve dry out.
  • VNS System Implant: Creation of Generator Pocket
    • Incision made with creation of subcutaneous pouch superior to pectoralis major
  • VNS System Implant: Creating the subcutaneous tunnel
    • The tunneler is inserted in the neck incision and passed to the chest incision. The bullet tip and then steel shaft are removed leaving the plastic sheath.
    Tunneling Direction
  • VNS System Implant: Passing the Lead
    • The connector pin end(s) of the lead are inserted into the sheath of the tunneling tool at the neck opening. The sheath is pulled out through the chest incision.
    Tunneling Direction
  • VNS System Implant: Lead position after being passed
    • After pulling the sheath from the chest incision, the connector pin(s) are removed. The helical electrodes remain near the neck incision.
  • VNS System Implant: Final Electrode/Anchor Tether Placement
    • Use of the integrated anchor tether helps prevent force transfer to the electrodes.
    Negative Electrode Positive Electrode Anchor Tether Cephalad   Caudal
  •  
  • VNS System Implant: Routine System Diagnostic Test #1
    • Perform a Lead Test to make sure both components are functioning
    • If Lead Test fails, check all connections.
  • VNS System Implant: Strain Relief Bend
  • VNS System Implant: Silastic Tie-Down
    • Lead strain relief bend completed with lead attached to fascia using tie downs
  • VNS System Implant: Inserting the Pulse Generator
    • Secure pulse generator with suture to prevent migration.
    • Logo may face up or down.
  • VNS System Implant: Routine System Diagnostic Test #2
    • After the skin is closed, and before breaking the sterile field, perform a confirmatory Lead Test
    • After Lead Test, perform a confirmatory interrogation to make sure that the Pulse Generator is set to 0 mA
  • VNS System Implant: Closure
    • To minimi s e scarring, a subcuticular closure is recommended for both skin incisions.
  • Thank you !!!
  • Back up slide
  • Who can benefit from VNS Therapy  ?
    • People who are not candidates for brain surgery
    • People who do not want to have brain surgery
    • People who failed brain surgery
    • People suffering from epilepsy who have developmental disability (MRDD)
    People suffering from difficult-to-control seizures People with all seizure types People of all ages: kids, teens, adults, elderly
  • Refractory Epilepsy Occurrence
    • More than 30% of patients continue to have seizures in spite of multiple adequate trials with pharmacologic therapy. Seizures may persist in terms of frequency, severity, or duration, or in all 3 aspects.
  • Seizure Reduction – LGS - Frost (2001) V d - Frost M. Epilepsia .2001;42(9)1148-1152. 38% 58% 0 10 20 30 40 50 60 > 50% > 75% Seizure Reduction (n=24) Patients (%) 6 Months after implant
    • n = 50
    • mean age = 13yrs
    • mean onset age = 1.4yrs
    • # of ADE before implant = 9
    • >50% reduction @ 1m = 42% 3m = 58.2% 6m = 57.9%
    50% reduction in 58% of LGS patients after 6 months
  • Seizure Reduction – Drop Attacks (LGS) - Frost V d - 55% 47% 0 10 20 30 40 50 60 70 80 90 100 1 m 3 m Mean Reduction (%) Drop Attack Seizures p<0.0001 p<0.0001 Frost M. Epilepsia .2001;42(9)1148-1152. 88% 6m p=0.0002
    • Data Analyzed by Drop Attack seizures
    88% of Drop Attack Seizures are reduced after 6 months
  • Seizure Reduction – Absence (LGS) - Frost V d - 73% 48% 0 10 20 30 40 50 60 70 80 90 100 1 m 3 m Mean Reduction (%) Absence Seizures Frost M. Epilepsia .2001;42(9)1148-1152. 81% 6m
    • Data Analyized by Atypical Absence seizures
    81% of Absence seizures are reduced after 6 months
  • Seizure Reduction - Tuberous Sclerosis - Parain
    • n = 10
    • age range = 7 ~ 20
    • mean age = 13
    • 5 ~ 19 seziures/day
    • Seizure duration reduction in 30% of patients
    V d - Parain D. Paediatric Neurology. 2001;25(3):213-216. 48% 90% 0 10 20 30 40 50 60 70 80 90 100 50% 90% seizure reduction (%) Tuberous Sclerosis % of patients For TS patients, 90% of patients had 50% reduction
  • VNS Therapy System: Implanted Components
    • New Implants
    • Models 102 & 302
    Battery Replacement For Dual Cavity Generator Models 102R or 101 & 300
  • Mechanism of Action
    • The locus coeruleus (LC) may be involved in anticonvulsant effect.
    • Induces progressive EEG changes
    • Bilateral changes in blood flow. .
    • Increased blood flow in the thalamus correlate with long-term seizure control
  • VNS Therapy System – Other Components
  • Recent Advances in VNS therapy
      • VNS & seizure control
      • VNS & early treatment
      • VNS & drug reduction
      • VNS & medical cost reduction
      • VNS & patient satisfaction
      • Safety & side effects
      • On-going research
    •  In the EAR group (< 5 years after onset), 15% reported no seizures with VNS Therapy at 3 months compared with 4.4% of those in the control group.
    •  one patient in five reported no seizures with a loss of consciousness, and one in three with complex partial seizures reported complete control of the complex partial seizures at 3 months with earlier use of VNS Therapy.
    Seizure Control – 3 months after implant
  • Seizure Control – 3 years after implant
    •  An open-label, long-term study of 454 epilepsy patients using data from all 5 VNS Therapy controlled, clinical trials. The study compared the percentage of patients with seizure reductions of 50% over a 3-year period.
    • The percentage of patients with 50% seizure reduction was 43% at 2 and 3 years.
  • Benefit of Early VNS Treatment – Seizure Control
    • Early Adjunctive Registry (EAR): n=120, VNS implant <5 yrs of 1st onset
    • Control group: n=2785, VNS implant>5 yrs of 1 st onset
    P=0.001 P<0.001 Ref: J.Ben Renfroe and James W.Wheless Neurology 59 (4), S26-S30, 2002
  • Medical Cost Reduction Resulted by AED / Surgery / VNS ERDMC In USD Ref: P. Boon et al. Epilepsia 43(1): 96-102, 2002
    • Epilepsy-related direct medical costs (ERDMC) include:
      • Cost of AEDs
      • Cost of visiting clinics
      • Cost of hospital admissions
      • Cost of lab tests
    P=0.0007 P=0.0036 VNS and Surgery both show significant decrease in ERDMC
  • VNS and Medical Cost Reduction – ICU / ER / WARD
    • Subject: 43 Patients
    • Method: Retrospective medical record
    • Sahlgenska University Hospital. Sweden
    Ref: Elinor Ben-Menachem et al. Neurology 59 (4), S44-S47, 2002
  • Patient Satisfaction of VNS v.s. AEDs
    •  Continuation rates at 3 years:
      • VNS: 72%
      • Levetiracetam: 37%
      • Topiramate: 30%
      • Lamotrigine: 29%
    • VNS Therapy are remarkably better than long-term continuation rates with other treatments for pharmacoresistant epilepsy
  • 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
  • Patient Identification
    • Patients who :
    • Have uncontrolled seizures despite 2 adequate AED trials?
    • Quality of life compromised due to uncontrolled seizures ?
    • Discontinue or switch therapies frequently?
    • Experience negative side effects associated AEDs?
    • Are not candidates for intracranial surgery?
    • Patient Identification Qualification form & Cyberonics Patient Registry
    • End-of-Service Replacement
    • If the answer to any of these questions is “yes,” you may have patients who could benefit from VNS Therapy.
  • Replacement of End-of-Service Generators (video)
  • VNS Therapy Surgical Complications Data on file. Cyberonics, Inc. Houston, TX; 2002. Data reported are for the most commonly reported surgical complications on all surgical cases including reimplants.
    • Post approval (n=17,019)
      • Infection (with and without explant) 1.3%
      • Hoarseness/temporary vocal cord paralysis 1.1%
      • Mortality 0.0%
  • Device Activation– Program Settings
    • Initial Activation – 2 weeks after implant
    • Initial program setting
        • 0.25 mA output current
        • 20-30 Hz frequency
        • 250-500 µ sec pulse width
        • ON 30 sec
        • OFF 5 minutes
    • Adjustment:
        • Slowly titrate output current over 4 weeks to 0.5-1.5 mA
        • Reduce pulse width from 500 µsec to 250 µsec
        • Again, try to increase output current and decrease pulse width
  • Advance Program Settings – Study Results
    • High setting is more effective than Low setting
      • (30 sec ON, 5 min OFF, 30 HZ(0.25-3.5mA)) vs (30 sec ON, 180 min OFF, 1 HZ(0.25-3.5mA))
    • Low setting were crossed over to high setting, a robust improvement in efficacy resulted: 21% to 40%
    • A significant improvement in efficacy was observed when:
      • Duty cycle (ON/ON+OFF time)  22%
      • OFF time  1.1 minutes,
    • A precise dose-response relationship for VNS therapy is still under investigation
  • Support from Cyberonic and CardioMed
    • Prognosis evaluation-PIQ
    • Patient education
    • Financial assistance
  • Agenda
    • What is VNS
      • Refractory Epilepsy
      • Mechanism
      • Picture of Product
    • Recent Advances in VNS therapy
      • VNS & seizure control
      • VNS & early adjunctive therapy
      • VNS & drug reduction
      • VNS & medical cost reduction
      • VNS & patient satisfaction
      • Safety & Side effects
      • Update research
    • Patient Identification & Selection
        • PIQ & Cyber data base
    • Implant Procedure
        • Procedure outline (replacement & new)
        • Pictures & movie
        • Possible complications
    • Program setting
        • Initial settings
        • Adjustment
    • Support from Cyberonic and CardioMed
  • Epilepsy-Epidemiology
    • Epilepsy is one of the most prevalent neurological disorders that can be effectively prevented and treated at an affordable cost. It is the most common serious brain disorder worldwide with no age, racial, social class, national nor geographic boundaries.
    • There are over 50 million sufferers in the world today, 85% of whom live in developing countries;
    • An estimated 2.4 million new cases occur each year globally;
    • At least 50% of cases begin at childhood or adolescence;
    • 70% to 80% of people with epilepsy could lead normal lives if properly treated;
    • In developing countries, 60% to 90% of people with epilepsy receive no treatment due to inadequacies in health care resources and delivery, and due to social stigma.
        • (Ref: http://www.who.int/mental_health/neurology/epilepsy/en/)
  • Cause of Epilepsy
    • Newborn: congenital malformation, brain injury during perinatal or encephalitis
    • Children and adolescent: injury from traumas, infections such as meningitis or encephalitis.
    • Adult and elders: brain tumor and stroke
    • (Ref: 最新癲癇病人手冊 關尚勇 2001)
  • Treatment Sequence for Refractory Epilepsy Surgery evaluation before VNS?
  • 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
  • Pulse Generator: Programmable Parameters Generator cycle is 24 hours per day.
  • Lead: The Electrodes and Anchor Tether --Negative Electrode --Positive Electrode --Anchor Tether NOTE: Sutures are for placement, not tying. (No metal/conducting electrode inside)
    • All lead models are currently available in two sizes based on helical inner diameter:
    • Model 302 (single pin of G102)
      • Model 302-20 (2.0 mm) Model 302-30 (3.0 mm)
    • Model 300 (dual pin of G102R, G100, G101)
      • Model 300-20 (2.0 mm) Model 300-30 (3.0 mm)
  • Lead: Physical Characteristics
  • Lead Models 300 & 302:
  • Vagus Nerve Schema with Lead Attachment Location Please Note: Drawing is not to scale and is for informational purposes only
  • Model 100 Single Pin Connector: Model 102 Prior/Fully Inserted
  • Dual Pin Connector: Model 102R Prior/Fully Inserted
  • Model 402 Tunneler
    • Contents:
      • 2 sleeves to accommodate both Lead models
      • Steel shaft
      • Steel bullet tip
  • Model 502 Accessory Pack
    • Contents:
      • Hex screwdriver
      • 4 tie-downs
      • Dual pin resistor for 101, 102R
      • Single pin resistor for 102
  • Programming System Components
    • A computer, Programming Software (Model 250), and Programming Wand (Model 201) communicate transcutaneously to the Pulse Generator
    • Easy to use
    • Used during
      • Surgical implant
      • Programming office visits
  • Model 201 Programming Wand
    • Model 201 Programming Wand
    • Intended for use only with the VNS Therapy System.
    • Hand-held device that transmits programming and interrogation information between a VNS Therapy Computer and the VNS Therapy Pulse Generator
  • Model 220 Magnets
    • Provide on-demand stimulation that may help abort or lessen the intensity of an oncoming seizure
    • Temporarily inhibit stimulation
    • Reset the Pulse Generator (in combination with the Programming Wand)
    • Test daily the functioning of the Pulse Generator
  • Cost Reduction after VNS Therapy
    • Epilepsy-related direct medical costs (ERDMC):
      • Cost of AEDs
      • Cost of visiting clinics
      • Cost of hospital admissions
      • Cost of lab tests
    Ref: P. Boon et al. Acta Neurochir 141:447-453, 1999 Pre- VNS Post- VNS (2 years) Range P value (Wilcoxon signed rank test) ERDMC US 8830 US 4215 US 615-11794 N=13 0.018 HP admission days 21 days 8 days 0-35 day N=13 0.023
  • 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
  • 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)
  • What is VNS
    •  An adjunctive therapy in reducing the frequency of seizures in patients whose epileptic disorder is dominated by partial seizures or generalized seizures, which are refractory to antiepileptic medication.
    • VNS Therapy delivers stimulation via a device implanted just under the skin in the left chest area. The pacemaker-like device sends mild, intermittent electrical impulses through a lead to the left vagus nerve, which then sends signals to the brain. Each device is programmed for the individual patient, and the patient has the ability to initiate or abort stimulation with the use of a hand-held magnet.
  • Patient Kit
    • Contents:
      • Patient Manual
      • 2 Magnets
      • Patient Emergency Information Card
    • To be given to patients immediately following surgery
  • New Benefits for 102 v.s 100
    • 1. 33% thinner
    • 2. 34% lighter
    • 3. single connector eliminate the risk of reverse polarity
    • 4. longer battery life (2X)
    • 5. longer warranty (2yr instead of 1yr)
    • 6. faster programming
    • 7. longer shelf life
  • The VNS Therapy System Components
    • Implement components:
      • Pulse Generator: Model 101, 102, 102R
      • Lead: Model 300, 302
    • Disposable components:
      • Tunneler Model 402
      • Accessory Pack Model 502
    • Programming and patient components:
      • Magnet Model 220
        • Watch-style (220-3) and Pager-style (220-4)
      • Programming Wand Model 201
      • Programming Software Model 250
      • Programming Computer
    No Latex in any product Pictures First
  • Patient assistance: Avenues program
    • AVENUES Program
    • Patient Videos
    • Website: www.vnstherapy.com
    • Power To Renew My Life Diary
    • VNS Therapy Phone Facts Teleconferences
    • Case Managers
  • Asystole from Lead Test in Surgery
    • Incidence of asystole during routine intraoperative lead test 1
      • Reported rate is estimated to be between 1 in 400 and 1 in 800 patients
      • Full recovery for all patients
    • Similar events were not reported in controlled, epilepsy clinical trials 2
    • Reason: anatomic differences, lead placement, anesthesia, or collateral current spread? 1,3
    1 Data on file. Cyberonics, Inc. Houston, TX; 2002. 2 Tatum WO, et al. Neurology. 1999;52:1267-1269. 3 Asconape JJ, et al. Epilepsia. 1999;40:1452-1454.
  • Program Setting: FAQ
    • When can I safely activate the device?
    • Ans: 2 weeks after surgery.
    • What are the most important things to remember when adjusting VNS parameters?
    • Ans:
      • monitor the patients for shortness of breath, throat tightness/discomfort, excessive hoarseness and discomfort with swallowing.
      • Follow the physician manual of Generator Sec 8 (approved by FDA)
      • Ensure the patient tolerance before leaving
    • How do I manage side effects?
    • Ans: Adjust pulse width first then the output current.
    • What are appropriate magnet settings?
    • Ans: Magnet settings should be programmed at 0.25 mA higher than the around-the-clock VNS therapy. Setting the output current of magnet higher than regular.
  • No Side Effects from AEDs and Safe
    •  No side effects associated with AEDs e.g.: sleeplessness, confusion, weight gain, memory loss
    • VNS Therapy is not associated with
      • interactivity toxicity 1,2
      • pharmacokinetic interactions 2
      • systemic neurotoxic effects 2
      • idiosyncratic reactions (rash, renal impairment, bone marrow suppression etc.) 2
    • No evidence of impaired fertility or harm to the fetus in animal studies 3 -> FDA granted approval VNS Therapy safety in women of childbearing age. The unique safety profile of VNS Therapy can contribute to the quality-of-life for patients. 4  1Henry TR. Neurology. 2002; 59 (suppl.4):S3-S14. 2Gates J, Huf R, Frost M. Epilepsy & Behavior. 2001; 2:563-567. 3Physician’s Manual: VNS Therapy Pulse Model 102 Generator. Houston, Texas: Cyberonics Inc.; 2003. 4Wheless JW et al. Neurology. 2002; 59 (suppl.4):S21-S25.
  • 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%
  • VNS chronology
    • 1988 EO1 Study-1st Human Implant
    • 1994 European Community Approval
    • 1997 5 Completed Controlled Studies (N=454)
    • 1997 US and Canadian approvals
    • 2004 >25,000 patients treated
  • Patient Selection
    • Limited success with any single AED or combination of AEDs 2
    • Response to first AED trial 2
    • Predictors related to intolerable side effects
    • Seizure frequency before initial therapy 2
    • Early age at onset 3
    • Cause or origin of seizures 2
    • Electroencephalographic (EEG) factors 3
    • Imaging with positron emission tomography (PET) 4
    • Cyberonic’s Patient Registry – PIQ for predicting treatment outcome.
    • 1Brodie MJ, Kwan P. Neurology. 2002;58(suppl 5):S2-S8. 2Kwan P, Brodie MJ. N Engl J Med. 2000;342:314-319. 3Ko TS, Holmes GL. Clin Neurophysiol. 1999;110:1245-1251. 4Dupont S, et al. Arch Neurol. 2000;57:1331-1336 .
  • Implant procedure of VNS system (video)
  • VNS Therapy - a breakthrough in treating difficult-to-control epilepsy
    • A clinically proven epilepsy treatment
    • Safe and has been used in over 50,000 patients
    • Helps to prevent seizures
    • Has minimal side effects
    • Can improve quality of every day life
    • Has long-term benefits
    • Is easy to live with
    • Gives people with epilepsy a sense of control over their lives
  • VNS Therapy A different mechanism of action
      • The mechanism of action of VNS Therapy might be:
        • Changes in metabolism of brain areas relevant to mood regulation
        • Alteration of key mood-regulating brain neurotransmitters 1,2
        • Changes in the HPA-axis 3
    1. George MS et al., Biological Psychiatry , 2000. 2. Dorr et al., The Journal of Pharmacology and Experimental Therapeutics , 2006. 3. O’Keane et al., Biological Psychiatry , 2005. 4. Data acquired from St. Louis University, analyzed at Medical University of South Carolina Center for Advanced Imaging Research by Xingbao Li, MD; 6 patients for 3 months of VNS Therapy, compared with baseline. Cortical/limbic brain specificity with VNS Therapy 4 Orbitofrontal cortex Left insula Mid-cingulate gyrus Left thalamus Left amygdala and hippocampus Position emission tomography (PET) P<0.05 for display, no significant decreases
  • VNS and Drug Reduction
    • 21 patients using VNS compared results to a case-matched control group in Tampa General Hospital Comprehensive Epilepsy Center
    Results : 1. 15 /21 patients decrease the usage of AEDs either in number or dose 2. Tiagabine was the most common AED reduced. Ref: W.O. Tatum et.al., Neurology 56: 561-563, 2001 n = 21 Dose reduction Dose remain 9 Patients w/ reduced number of AEDs 4 5 12 Patient w/ same number of AEDs 6 6
  • 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! “ ”
  • 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
  • Seizure Reduction Increases with Time Sperner (2002)
    • n = 95 in Europe
    • age range = 3 ~25yrs
    • mean age = 10yrs
    • onset, mean = 1.2yrs
    • duration, mean = 8yrs
    • 86% mentally retarted
    • 20% had surgery
    • 23% LGS
    V d - Sperner J. Neuropediatrics 2002;33:A22-A23. Reduction improves over time in addition to QoL improvement Patients (%) Patients with ≥50% Reduction in Seizures 50% 34% 0 10 20 30 40 50 60 3 m n=42/122 12 m n=42/84 54% 24 m n=20/37
  • 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.
  • 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. “ ”
  • Magnetic empowerment - a unique benefit of VNS Therapy 
    • By passing the special Magnet over the VNS Therapy device when you feel a seizure coming on, you may be able to:
      • Stop your seizure
      • Shorten your seizure
      • Decrease the severity of your seizure
      • Improve the drowsy post-ictal/
      • recovery period following your seizure
    Brady, 8 years of age VNS Therapy since 2000 The magnet has given us control over Brady’s seizures, where with drugs we had no control. You couldn’t put more medication in him to get his seizures to stop – you’d have to worry about overdosing. The magnet doesn’t hurt him. He has a magnet at school and we trained his teachers to use it. Brady’s mum “ ”
  • VNS Therapy  quality of life benefits
    • Even in patients who are not responders (less than 25% seizure change), quality of life improves
    VNS Patient Registry: January 25, 2002 Data on file, Cyberonics, Inc. % of Registry Patients Better or Much Better * Fewer than 8% of patients reported any single measure worse
  • 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