1. Mahmoud Taha MD KFSH-Dammam, KSA
VNS for epilepsy
Mahmoud Taha MD
KFSH-Dammam, KSA

3. 50% of intractable would be suitable for surgery
Epilepsy surgery
50% of intractable would be suitable for surgery
<10% of those suitable for surgery currently have operation in the UK
Epilepsia May;44(5):673-6

4. Criteria for medically intractable epilepsy
Quality of life
seizures interfere with the patient’s life enough for him/her or guardian and not the physician to consider surgery after counseling about risks
Adequate medical treatment
trial to toxicity with at least two major anti-epileptic drugs
patients uncontrolled after 2 years of medical management are unlikely to become seizure free without surgery even with newer drugs

5. Aims of surgery
Reduction of seizure frequency
Improvement of seizure pattern
Reduction of anticonvulsants drugs
Improve QOL

6. Pre-surgical Evaluation
Phase 1: Non-invasive
Phase 2: Invasive
Clinical assessment
Neuroimaging:
MRI, PET,SPECT
Electrophysiology
Routine EEG
24 H intensive video
Neuropsychological tests
Psychsocial evaluation
Electrophysiological
24 h intensive video monitoring( epidural, subdural, intracerebral electrodes)
Neuropsychological tests:Intracarotid amobarbital test
( WADA test)

7. invasiveness Resective surgery removal of diseased hemisphere
removal of diseased lobe
removal of epileptogenic tissue
Disconnection surgery:
functional hemispherotomy
division of corpus callosum (callosotomy)
multiple subpial transection
Functional operations:
neurostimulation (vagus nerve , VNS®)
Deep brain stimulation
Radiosurgery:
stereotactic lesioning
stereotactic radiosurgery
invasiveness

8. VNS: Historical background
1938, Bailey and Bremer reported that
vagal stimulation causes EEG changes
J Neurophysiol. 1938;1:
1951, Dell and Olson studied the route taken by the ascending influence from the nucleus of tractus solitarius (NTS).
Soc Biol Fil. Jul 1951;145(13-14):
1985, Zabara reported the effects of VNS on seizure control in animal studies.
1988, Penry, Wilder, Ramsay, and colleagues performed the first implant of a vagal stimulating device into a human.
Electroencephalography. 1985;61:S162

9. VNS Trials and approval
Two pilot studies (E01, E02), 14 patients found the mean percentage of seizure reduction in the patients to be 46.6%.
a randomized active control study (E03) was performed in 1992
In 1994, the European Community approved the use of VNS for seizure prevention and control.
1997, FDA approved the use of VNS as an adjunctive treatment for refractory partial-onset seizures in adults and adolescents older than age 12 years.

10. VNS: mechanisms of action
The precise mode of action of VNS, like that of the antiepileptic drugs (AEDs), is not known.
Areas possibly activated by VNS
include the medulla, cerebellum,
parabrachial nucleus, locus ceruleus,
hypothalamus, thalamus amygdala,
hippocampus, cingulate gyrus,
and contralateral somatosensory
cortex.

11. VNS: mechanisms of action (animals)
VNS inhibits seizures in multiple animal models of epilepsy.
VNS requires stimulation of C fibers, which is achieved with high-intensity, high-frequency stimulation; it produces desynchronization of the cortical EEG.
Investigators have suggested that VNS increases seizure threshold by causing widespread release of GABA and glycine in the brain.

12. VNS: mechanisms of action (human)
Ben-Menachem et al measured amino acid and neurotransmitter metabolite concentrations in cerebrospinal fluid (CSF) samples of patients on clinical trials of VNS before and 3 months after VNS placement and found paradoxical results.
On the other hand, free and total GABA levels were higher after long-term VNS
Epilepsy Res. Mar 1995;20(3):221-7
In 1993, McLachlan posited that VNS decreased cortical epileptiform activity indirectly by influencing the reticular activating system
Epilepsia. Sep-Oct 1993;34(5):918-23

13. fMRI Significant bilateral changes in blood flow: Thalamus (increase)
Hypothalamus (increase)
Insular cortex (increase)
Amygdala (decrease)
Hippocampus (decrease)
Posterior cingulate gyri (decrease)
Epilepsia. 1998;39(9):

14. Who is suitable? VNS: intractable epilepsy: 2 years, 2 drugs
Pre-op evaluation:
No resective lesion or multiple
Or failed resection
seizure type
not defined
age limit

16. VNS: technique aspects

18. VNS: stimulation parameters
Output current: mA (0.25mA steps)
Frequency: Hz
Pulse width: sec
On time: sec
Off time: 12 sec to 270 min
Independent programming of
stimulus parameters “on demand”
using magnet

20. Combined data, E01 - E05, n=440 VNS: how effective

21. Neurosurg Focus. 2012 Mar;32(3):E12. doi: 10.3171

22. VNS: predictive factors
a meta-analysis of 74 clinical studies with 3321 patients suffering from intractable epilepsy
average reduction of 45%
36% reduction in seizures at 3-12 months
51% reduction after > 1 year
Patients with generalized epilepsy and children benefited significantly.
Post-traumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome
J Neurosurg Dec;115(6):

23. VNS: long-term outcome
In 24 children (mean age y), the mean percentage of seizure reduction after 6 months to 7 years of treatment were as follows :
• % (n=24) (sixth month)
• 32% (n=20); (first year)
• 42% (n=16) (second year)
• % (n=11) (third year)
• 52% (n=10) (fourth year)
• 60% (n=8) (fifth year)
• % (n=8) (sixth year)
• % (n=6) (seventh year)
Eur J Paediatr Neurol. Jul 2010;14(4):334-9

24. VNS: Quality of life 40 children with MR/DD and refractory fits
VNS, 2 years f/up
At least 50% reduction in 25% patients
Medication reduced from 3.3 per case to 2.3
overall quality of life improved for the majority of subjects
using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores
Epilepsy Behav May;6(3):

25. VNS: cost effectiveness
Cost of each VNS is $ 10000
43 patients, refractory epilepsy have VNS
Unplanned hospital costs : ER, ICU, bed stay..
18 months pre VNS and 18 months post VNS
$ 3000 saving with VNS regardless response to VNS treatment.
Neurology Sep 24;59(6 Suppl 4):S44-7

26. VNS: Side effects
5%: voice alteration/hoarseness, cough, throat pain, nonspecific pain, dyspnea, paresthesia, dyspepsia, vomiting, infection
Most of these adverse effects have a negligible impact on the quality of life of treated patients and are reported as mild 99% of the time.
The effects appear during stimulation and tend to diminish over time
The NCP device is not affected by microwave transmission, cellular phones, or airport security systems.

27. conclusions VNS insertion is safe and effective Cost effective
Small side effects
Mechanism?
Small RCT especially in children
Long-term?