The RNS system is an FDA-approved treatment for drug-resistant epilepsy that involves surgically implanting a neurostimulator device to detect and respond to seizure activity. Clinical trials found that the RNS system provided a median seizure reduction of over 37% within 3 months for treated patients compared to a 25.2% reduction for the sham group. Long-term follow-up over 7 years found the RNS system maintained seizure control effectiveness and was safe, with no chronic neurological effects reported. The RNS system may be an option for patients who have failed two or more anti-seizure medications and are not candidates for resective epilepsy surgery.

1. RESPONSIVE NEUROSTIMULATION (RNS)
FOR INTRACTABLE EPILEPSY
James R. White, MD

2. RESPONSIVE NEUROSTIMULATION
(RNS)
MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

4. Patient Selection
• The RNS System is indicated for patients who:
• Have failed 2 medications
• Have partial onset seizures that are localized to 1 or 2 foci
• Other considerations:
• Patients who are not resective surgery candidates
• Temporal lobectomy patients can have a 70% chance of seizure freedom
• Patients at risk of neurological/cognitive deficits with resection
• For example, seizure onset over language cortex
• Equally effective across variety of patients:
– Treated and not treated with VNS
– Treated and not treated with epilepsy surgery
4

5. WHAT HAPPENS TO PATIENTS
WITH NEW ONSET EPILEPSY?
• % of patients controlled
with:
• First AED:
• 47%
• Second AED:
• 13%
• Third AED/combination
therapy
• 4%
• Total controlled: 64%
• Total not controlled: 36%

6. RNS® System Clinical Trials
6
Feasibility Trial
65 patients implanted
Pivotal Trial
Double blind RCT
191 patients implanted
Open Label Long-term Treatment Trial
7 year follow on study, 230 enrolled
New Post-approval study
300 pts to be enrolled at 30 centers
The safety and efficacy of the RNS® System is supported by Class I Evidence
from the prospective, double-blind, randomized, controlled pivotal trial.
Patients prospectively followed through 9 years, currently representing 1389
patient implant years.

7. Established seizure control that improves
over time
•Median % Seizure Reduction •Seizure-Free
Intervals
• ≥ 3 months: 37%
• ≥ 6 months: 23%
• ≥ 1 year: 13%
7
Heck CN, et al. Epilepsia, 2014.
Bergey GK, et al. Neurology, 2015.

8. Patient’s seizures are not
completely controlled.
• Most patients have a significant improvement in
seizures, but are not “cured”.
• 12.9% had at least 1 seizure-free period of 1 year
or longer.
• No participants were seizure-free over the entire
follow-up.
MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

9. PLACEBO EFFECT DURING PIVOTAL TRIALS
• The treatment group was compared to the sham control group:
• Treatment group: Device is fully functioning, stimulating when seizure
activity detected.
• Sham group: Has device implanted, but device is not stimulating.
• During blinded evaluation period, sham group was noted to
have seizure reduction:
• First month: 25.2% seizure reduction
• Third month: 9.4% seizure reduction
• Treatment group still significantly better than sham group
• This placebo effect is interesting and seen in other device
studies.
• Makes it more of a challenge to show that the device works!
• Shows how important it is have a control!

10. RNS® System is effective for both mesial
temporal and neocortical seizure onsets
10
Mesial temporal lobe onset (n=106)
• 70% median reduction in seizures1 (LOCF*)
• 66% responder rate1 (95% CI 57%–74%)
• Improvements in memory for mesial temporal
onset seizures2 (p<0.005)
Neocortical onset (n=122)
• 58% median reduction in seizures3 (LOCF*)
• 55% responder rate3 (95% CI 46–63%)
• Improvements in naming for neocortical onset
seizures2 (p<0.001)
*Last observation carried forward analysis, last 3 months
1 Van Ness, P, et al, American Epilepsy Society abstract, 2015
2 Loring DW, et al, Epilepsia, 2015
3 Jobst B, et al, American Epilepsy Society abstract, 2015

11. Improvement in all quality of life domains
Meador et al, Epilepsy & Behavior, 2015
• Total QOLIE-89
statistically
significantly higher
than baseline
• Statistically
significant group
improvements in
every subdomain
11

12. Long-term Safety
• Rate of serious adverse events similar to that of deep
brain stimulation for movement disorders
• Infection risk 3.5% per neurostimulator procedure1
• All reported infections were soft tissue
• No chronic neurologic or medical consequences
• Implant related hemorrhage 2.7%2
• No persistent, clinically significant neurologic sequelae
12
1 Based on device related SAEs
2 Not seizure related
Bergey et al., Neurology, 2015
Morrell et al., Neurology, 2011

13. MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

14. Procedure Overview
14
• Leads are placed at the seizure focus
– up to 2 leads are connected to the neurostimulator at once
– up to 4 leads can be implanted
• Neurostimulator is implanted into skull, underneath scalp
– Device conforms to skull, invisible underneath hair
• Standard stereotactic neurosurgical techniques and equipment

16. MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

17. Step 1: Personalized Detection
17
LHip
RHip
LHip
RHip
Physician determines which patterns will be detected

18. Detection and Responsive Stimulation
(Hippocampal Epileptiform Discharge)
18

19. RNS Neuropsych Outcomes
• Loring et al, Epilepsia, 2015
• Neuropsychological data was collected during the
open –label arm of the RCT of RNS.
• Primary Cognitive tests:
• Boston naming
• RAVLT
• Tests were performed at baseline, year 1 and year
2.
• 191 patients implanted in the Pivotal Trial.
• 175 patients had baseline neuropsych and year 1, year
2 or both.
MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

20. RNS Neuropsych Outcomes
• No significant cognitive declines noted through 2
years.
• Naming:
• All patients: significant improvement (p<0.0001)
• Neocortical group: significant improvement (p<0.001)
• Mesial temporal lobe group: no significant change
• Verbal learning:
• All patients: significant improvement (p<0.03)
• Neocortical group: no significant change
• Mesial temporal lobe group: significant improvement
(p<0.005
MINNESOTA EPILEPSY GROUP
SEIZURE CARE FOR ALL AGES

21. CONCLUSIONS
• The RNS is another weapon in our arsenal to try to
improve seizure control/quality of life in our
patients with intractable epilepsy.
• Careful selection of optimal patients is important:
• Good seizure localization
• Patient is not a resective surgery candidate
• RNS appears relatively safe from a memory
standpoint.

22. THANK YOU!