VAGAL NERVE STIMULATION

INTRODUCTION

• a new non-pharmacological antiepileptic therapy, approved in 1997 by the US Food and Drug Administration

• adjunctive therapy for adults and adolescents over 12 years of age whose partial onset seizures are refractory to antiepileptic medications.

Schematic drawing of the general placement of the vagusnerve stimulation system and bipolar stimulating lead

VNS Therapy: components

• Programmable pulse generator• bipolar lead• programming wand with accompanying

software • tunnelling tool • hand-held magnets

PULSE GENERATOR&BIPOLAR LEAD

The Model 400 NCP Tunneling Tool is used during implantation to

create a subcutaneous path between the device in the chest and the vagus nerve in the neck

Programming wand

MAGNETS

procedure

• Incisions1&2• Electrode pin placing• Vagus nerve connection• Generator connection• Checking system• Setting parameters• Replacement of generator

VNS

Lead connections close-up

Use of programming wand to adjust generator stimulatorparameters

programming

stimulation parameter settings

Vagus nerve anatomy andmechanism of action of VNS

Mechanism of action

• NTS-PBN-THALAMIC CIRCUIT• HIGH FREQUENCY STIMULATION-

UNMYELINATED FIBRES-EEG DESYNCHRONIZATION

• LOW FREQUENCY STIMULATION-MYELINATED FIBRES-EEG SYNCHRONIZATION

Mechanism of action

• In 1993, McLachlan posited that VNS decreased cortical epileptiform activity indirectly by influencing the reticular activating system.

• Krahl et al demonstrated that the anticonvulsant effect of VNS could be reduced experimentally by lesioning the locus ceruleus.

• Henry et al reported that VNS causes measurable changes in cerebral blood flow in the cerebellum, thalamus, and cortex and may activate inhibitory structures in the brain

Indication

• FDA indication: "... adjunctive therapy in reducing the frequency of seizures in adults and adolescents over 12 years of age with partial onset seizure, which are refractory to antiepileptic medications."

• Although the FDA indication for VNS excludes other types of epilepsy (ie, those without partial seizure), most epileptologists agree that the VNS indications are probably broader than that

indications

• CPS• GTCS• LGS• EPILEPTIC ENCEPHALOPATHIES• ATONIC • ABSENCE• JME

Efficacy, LABAR etal

• 24 pts,-medication resistant GTCS• Idipathic-7,symptomatic -17• Seizure frequency reduced by 46% after 3

months,• 11 pts had >50% reduction

Hosain etal in LGS

• AGE 4-14,13 PTS• 52% REDUCTION IN SEIZURE RATE IN 6

MONTHS• 3 HAD >90% REDUCTION• 2 HAD >75% REDUCTION• ONE HAD >50% REDUCTION

MURPHY etal,

• 12 children • 4-16 yrs,medically&surgically refractory

seizures• 5 had >90% red.• 4 pts able to reduce AED doses

MURPHY etal,

• 60 children ,pharmacoresistant epilepsy,27%-GTCS

• After 6 months med.red.in frequency of seizures 31%

• After 12 months 34%• After 18 months 42%

PARKER etal,

• 16 children with epileptic encephalopathy• 50% red. In 1yr significant improvement in• EEG• adaptive behaviour• QOL• language performance

PATWARDAN etal,

• 38 children• 10-18 months follow up• Seizure reduction in atonic-80%,absence -

65%,CPS-48%,GTCS-45%

Sirven etal,

• Refractory epilepsy in 45 pts• 50 yrs or older• After 3 months,12 had >50% red• At 1 yr 21 had >>50% red

RESPONDER RATES.E03,E05 STUDIES

EFFICACY

LONG TERM CONTROL

responder rates for several of the newer AEDs with VNS

compares responder rates for several of the newer AEDs with VNS. Odds ratios (OR) and associated 95% confidence intervals for at least a 50% decrease in seizure frequency in response to gabapentin,lamotrigine,topiramate,tiagabine, or VNS

OTHER BENEFITS

Non epileptic indications

• ALZHEIMER’S DISEASE• OBESITY• BIPOLAR DISORDER• OCD• PTSD• CHRONIC MIGRAINE• ANXIETY DISORDERS

Safety&tolerability

• Mechanical and electrical safety• Environmental considerations• Laboratory values• Long-term safety and tolerability,

(mortality,pregnancy,swallowing defects,obstructive sleep apnea)

• Effects on mood and behaviour in patients with epilepsy

safety

Adverse events,E05 STUDY

Clinical use of VNS for epilepsy

Clinical usage,programming

• Increments of current• Reviewed after 6-9 months• Off time reduction• Rapid cycling

Efficacy of rapid cycling vagus nerve stimulation in

pharmaco-resistant epilepsy

• Rapid cycling is more efficacious than SC in pediatric group, but not in adult group. Lennox-Gastaut syndrome in pediatric patients yields a greater response to RC.

Suresh G GURBANI etal,Neurology Asia 2004;

To conclude

• Untill 2008;nearly 43,000 pts were treated with VNS WORLD WIDE

• Patient education• Surgical implantation• Follow up programming visits• Titrate stimulation