Neuromodulation for Epilepsy
Vagus nerve stimulation
3
 MRI/diathermy safety recommendations
 Head or extremity scan only; coil =
transmit/receive
 Set output + magnet to zero mA before scan
 No MRIs on patients with lead breaks
 No diathermy (shortwave, microwave,
ultrasound) on VNS patients
Physician’s Manual. Houston, TX: Cyberonics, Inc.
4
Vagus nerve stimulation
8
Krahl S, et al. Epilepsia. 1998;39:709-714.
9
•
•
•
11 partial epilepsy patients received VNS
Upon initial VNS activation, each had 015H20-PET cerebral blood flow scans
Increased thalamic blood flow bilaterally
upon initial VNS activation correlated with
subsequent decreased seizures during 3
months of treatment (p<0.01)
(Henry et al. 1999)
VNS activation prolongs transcranial
magnetic stimulation cortical silent period
VNS OFF
108.9 ms
VNS ON
169.6 ms
Dean et al. 2001
Vagus nerve stimulation
Mean Decrease in Seizure Frequency Versus Baseline
Reduction (%)
30
28%
20
15%
10
0
Low (n=102)
P=0.04
Handforth A, et al. Neurology. 1998;51:48-55
High (n=94)
Patients with >50% Reduction in Seizures
50
Patients (%)
40
43.2%
42.7%
2 years
3 years
36.8%
30
23.0%
20
10
0
3 months
1 year
Last Visit Carried Forward (n=440)
Morris et al., Neurology. 1999;53:1731-1735.
Mean % Change in
Seizure Frequency*
Time
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
-50
6 Months
(n=47)
2 Years
(n=38)
-22%
-55
*Last visit
1 Year
(n=47)
-26%
-28%
3 Years
(n=35)
5 Years
(n=30)
7 Years
(n=17)
10 Years
(n=17)
12 Years
(n=12)
-25%
-30%
-42%
-49%
-52%
carried forward (LVCF)
complex partial seizures, and secondarily generalized tonic clonic seizures
†Simple partial seizures,
Uthman BM, et al. Neurology. 2004;63:1124-1126.
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Vagus nerve stimulation
Patients (%)
70
Month 3*
60
Year 1†
50
Year 2†
40
Year 3†
30
20
10
0
Hoarseness
*3-month results (high
Cough
Paresthesia
Dyspnea
stimulation only, n=152). Physician’s Manual, VNS Therapy Pulse Model 102
Generator, Cyberonics, Inc.; June 2002.
†Year 1, 2, and 3 results (all study patients, n=440). Morris GL III, Mueller WM. Neurology.
1999;53:1731-1735.
84 implants, patients < 19 years old
3 infections requiring explant
3 superficial infections which
resolved with antibiotics
2 revision surgeries due to lead
fractures
(Smyth et al., 2003)
VNS SUDEP rate=4.1/1000
patient years
Resective surgery candidates
SUDEP rate=9.3/1000 patient
years
(Annegers et al., 2000; Dasheiff et al., 1986)
8 cases of asystole during intraoperative
lead test
 2 completed surgery, 6 surgery stopped
 No morbidity or mortality
 All with lead test current 1.0 mA
 Now 103 and 104 lead test current is 0.25
mA; no recurrence

( Ali et al., 2004; Tatum et al., 1999; Asconape et al.,1999)
PSGs on 4 VNS patients (1 with OSA)
More apnea and hypopnea during “on”
phase of duty cycle
1 OSA patient, VNS increased AHI from
4 to 11.3/hour
3 non-OSA patients, all AHI < 5/hour
No apnea/hypopnea with VNS at 20 Hz
Vagus nerve stimulation
60
50
40
Levi. Added n=151
Oxcarb. Added n=46
30
Zono. Added n=71
Same AEDs n=269
20
10
0
% sz change
Patient category
VNS
Case-matched control
Total number of patients
21
21
AED dose reduced
10 (48%)
2 (10%)
AED number reduced
9 (43%)
0 (0%)
Failed additional AED
4 (19%)
12 (57%)
Mean follow-up=13.2 months
(Tatum et al., 2001)
Vagus nerve stimulation
Vagus nerve stimulation
Programmable functions [initial]
Duty cycle
change, 3
mo vs. 12
mo
Number
of
patients
Median %
Median %
change szs change szs
@ 3 months
@ 12
months
Off > 3.0
min/Off > 3.0
min
174
-45%
-63%
Off > 3.0
min/Off < 1.8
min
71
-40%
-50%
Off < 1.8
min/Off < 1.8
min
21
-67%
-80%
Treatment A
Treatment B
Treatment C
On/Off time
7 sec/18 sec
30 sec/30 sec
30 sec/3 min
# Patients
19
19
23
Mean
current, mA
50%
responder
rate
0.87
0.80
0.93
31.6%
31.7%
26.1%
Seizure changes
Treatment group
Control group
Improved
Not Improved
52.5% of seizures
47.5% of seizures
40.7% of seizures
59.3% of seizures
(Morris 2003)
Vagus nerve stimulation






Epi. duration
Age
Epi. onset age
Prior epi. surgery
# prior AEDs
Concomitant AEDs





Epi. syndrome
Gender
Seizure rate
# current AEDs
# seizure types
Labar 2002
60
50
% of Patients
51%
40
EA (n = 120)
Control (n = 2785)
50%
*P=.001; †P<.001
35%
30
28%
26%
20
14% *
15%
10
0
4%
50
75
90
†
100
Reduction in Seizure Frequency, %
Renfroe JB and Wheless JW. Neurology. 2002;59(suppl 4):S26-S30.
32
Figure 1. Vagus nerve stimulation (VNS) efficacy in the mature adult.
Sirven J et al. Neurology 2000;54:1179-1182
45 patients > 50 years of age
A=3 months, all patients
B=12 months, study patients
©2000 by Lippincott Williams & Wilkins
Should I recommend VNS?
Yes-for patients with…
Should I recommend VNS?
Yes-for patients with…
Should I recommend VNS?
No-for patients with…
How do I manage VNS settings?
No specific stimulation is superior
How do I manage VNS settings?
No specific stimulation is superior
Video: A vagus nerve
stimulator patient’s
experiences
Neuromodulation for Epilepsy
 Transcutaneous VNS for 1 hour
three times per day
 5/7 patients had less seizures in
months 7-9 compared with baseline
 2/7 patients had more seizures in
months 7-9 compared with baseline
Epilepsia
Volume 47, Issue 7, pages 1213-1215, 19 JUL 2006 DOI: 10.1111/j.1528-1167.2006.00594.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2006.00594.x/full#f1
Figure
TRIGEMINAL NERVE STIMULATION FOR EPILEPSY:
LONG-TERM FEASIBILITY AND EFFICACY.
DeGiorgio, Christopher; Murray, Diana; Markovic,
Daniela; Whitehurst, Todd
Neurology. 72(10):936-938, March 10, 2009.
DOI: 10.1212/01.wnl.0000344181.97126.b4
Figure Adjusted mean daily seizure rate across timeBars
indicate standard error = 0.64.
©2009 American Academy of Neurology. Published by LWW_American Academy of Neurology.
2
Responsive Neurostimulator
(Morell 2011)(Neuropace)
Deep Brain Stimulation
for Epilepsy
(Fisher et al., 2010)(Medtronic)
30%
Control starts stimulation
Randomization
Active (n=43)
Median total seizure frequency percent
change from baseline
Control (n=43)
10%
Blinded Phase
Unblinded Phase
-10%
-30%
-50%
-70%
-90%
Baseline
Operative
M onth
1-2
M onth
2-3
M onth
3-4
M onth
4-5
M onth
5-6
M onth
6-7
M onth
7-8
M onth
8-9
M onth
9-10
M onth
10-11
M onth
11-12
M onth
12-13
1-month grouping
Includes subjects with at least 70 days of diary in each 3-month period
(ie, Mo 1-4, Mo 4-7, Mo 7-10, and Mo 10-13)(Fisher et al., 2010)
48
Thanks for your
attention.