VNS use for the treatment of refractory Epilepsy Anny Laforme Joanna Wai Ling Ma
VNS use for the treatment of refractory
Epilepsy
Anny Laforme
Joanna Wai Ling Ma
Content of the presentation
• Define refractory epilepsy
• Overwiew of available epilepsy treatments
• Adjunctive treatments for refractory epilepsy
• Vagus nerve stimulation
Definition of pharmacoresistant epilepsy
(World Health Organisation)
• Failure of 2 AEDs at therapeutic doses (efficacity and tolerability)
Epidemiology
• General population
• 0,4 to 1% of population has Epilepsy
• 10% of the population will experience seizure once in the lifetime
• Treated Epilepsy patients
• 60% are seizure free or have normal fonctionning with light limitation secondary to seizures
• 40% are limited in their fonctionning because of uncontrolled seizures
Ref: Canadian epilepsy alliance
Treatments
Pharmacologic Surgical
• Lifelong
• Possible side effect
• Numerous available combinations
• Low risk for health
• Only for refractory epilepsy
• Risk related to surgary and surgical site
• Varilable healing success rate
• Higher efficacy to control seizure than AED in
refractory Epilepsy (especialy in Temporal
region)
A Randomized, Controlled Trial of Surgery for Temporal-Lobe EpilepsySamuel Wiebe, M.D., Warren T. Blume, M.D., John P. Girvin, M.D., Ph.D., and Michael Eliasziw, Ph.D. for the Effectiveness and Efficiency of Surgery for
Temporal Lobe Epilepsy Study Group, N Engl J Med 2001; 345:311-318August 2, 2001DOI: 10.1056/NEJM200108023450501
Pharmacologic treatments
Factors influing AED choice (ILAE)
Specific AEDs variables Patient specific variables None-specific variables
• Type of epilesy
• Efficacity of AEDs
• Side Effects
• Idiosyncratic reaction (unusual
induvidual reaction to a drug)
• Chronic Toxicity
• Teratogenicity
• Pharmacocinetic
• Potential interractions
• Formulations
• Genetic
• Age
• Gender
• Comedication
• Coorbidity
• Insurance plan
• Physical capacity/ limitation
• Availability
• Cost
Surgical Treatments
Resective surgery VNS
• Multiple evaluations
• None surgical epilepsy area (focus)
• Possible implantation of electrods if non-
lesional epilepsy
• Surgical risk (infection, complication…)
• Irreversible
• None invasive
• All epilepsy type
• Possibility to ajust parameters
VNS fonctionning
Implanted generator with electrodes
transmitting stimulations to the
patient vagus nerve which send signal
to the brain.
Cont’d
• Action mecanism still uncertain
• Might decrease brain excitability
• Might desynchronize brain electricity
• Might modify the expression of neurotransmetors
• Might increase blood flow to the brain
Cont’d
• Efficacy increase in time
• Also use for refractory depression: VNS was first used to treat depression.
They notice a decrease of seizure in epileptic patient with depression
VNS programmation
Permanent setting (Regular treatment) On demand treatment
• Current
• Signal frequency
• Pulsation width
• Signal lenght (Total lenght-many pulsation per
signal)
• Inactive time
Regulation with magnet
• Current
• Pulsation width
• Signal lenght (Total lenght-many pulsation per
signal)
Parameters Unit Range Usual
Current Milliamps (mA) 0-3,5 1-2
Signal frequecy Hertz (Hz) 1-30 20-30
Pulsation Width Microseconds (µsec) 130-1000 250-500
Signal lenght Seconds (sec) 7-60 30
Inactive time Minutes (min) 0,2-180 5
Magnet
• Better side effect management for the patient and
family
• Stimulation on demand
• Facilitate post ictal period
• Stop stimulation by the patient in case of important
side effect
Side Effect
• Increase coughing
• Voice alteration
• Neck pain
• Dysphagia
• Side effect occur during stimulation only
• Side effect decrease over time
• Side effect can be control with ajustment of the device and by the magnet use
Cont’d
• No cognitive side effect
• No habituation (No decrease of efficacity)
• Efficacity increase in time (longue term use)
Dosing Notes
• Recommandations:
• Wait 2 weeks after the implant procedure before activating the device
• More office visits for the first few months to track patient response and side effects and
adjust stimulation parameters
• Alwayse dose to patient tolerance and ensure that the patient can tolerate settings
before leaving the office
• Give the patient time to adapt before making additionnal settings adjustment
Benefit
Increase of efficacy overtime
Efficacity
Quality of life
Positive impact of health care utilisation
PuLsE
Cont’d
• Objective:
• To evaluate whether VNS as adjunct to best medical pratice is superior than best
medical practice alone in improuving long therm health related quality of life
Cont’d
• Method:
• Prospective study
• Randomize
• Parallel group (1:1)
• Open-Label
• Long-Term
• 28 sites (Europe and Canada)
• Findings based on 96 subjects that have completed the initial phase and at least one follow-up between 3-12 months post intervention
Cond’t
• Endpoints
• Seizure control
• Adverse Event
• Health related Quality of live in Epilepsy inventory (quality of life score- QOLIE-89)
• Depression scales (CES-D and NDDI-E)
• Clinical Global Impression- improvement scale (CGI-I)
• AED load (quantity)
Cond’t
• Results:
Positive Neutral Negative
Significan diffrence in favor
of VNS + BMP
HRQOL (quality of life)
Seizure frequency
CGI-I (global impression)
Depression scales
AES load
Adverse Event (Side effect
related to surgery)
Cond’t
• Conclusion
• VNS therapy as a treatment adjunct to BMP in patient with pharmaco resitance focal
seizures was associated with a significan improvement in HRQOL compared with BMP
alone
Question? Comment?