vns use for the treatment of refractory epilepsy · 2017-11-05 · vns use for the treatment of...
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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?