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?