We propose cortical electrical stimulation therapy of a conceptually novel type. We systematically determine individual settings, stimulation site and seizure detection algorithm in a predictive model. In REC2Stim (Rational Extra-eloquent Closed-…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean and maximum duration of the seizure-free interval, motor performance, and
quality of life at the end of the study compared to these parameters prior to
implantation.
Secondary outcome
Spectral content in a time window prior and post stimulation, number of
interictal epileptiform discharges in a time window prior and post stimulation
Background summary
People with central lobe epilepsy (CLE), with seizures arising from the
precentral and postcentral gyrus, typically show a high rate of convulsive
seizures that do not respond to anti-epileptic drugs, with large impact on
quality of life. They often seek surgical relief, but since the area contains
the body*s indispensable sensorimotor representation, CLE surgery will lead to
permanent functional deficits. Surgical modifications such as multiple subpial
transections have rendered only 16% of the patients seizure free. Cortical
stimulation case studies in CLE have shown seizure frequency reduction of more
than 90%, but in our experience, stimuli in the central lobe can hardly be
applied without interfering with motor function. This means that patients with
CLE end up in a quandary without therapeutic solution.
Study objective
We propose cortical electrical stimulation therapy of a conceptually novel
type. We systematically determine individual settings, stimulation site and
seizure detection algorithm in a predictive model. In REC2Stim (Rational
Extra-eloquent Closed-loop Cortical Stimulation), at the start of a seizure, a
train of electric pulses is delivered to a nearby extra-eloquent area connected
with the epileptogenic area within the sensorimotor cortex. Success will
constitute a therapeutic modality for pharmacoresistant patients with an
epileptic focus in eloquent area.
Study design
This is a prospective study.
Intervention
Clinical intracranial EEG monitoring (normally 7-10 days) will be prolonged for
two days, for systematic testing of different stimulation settings and their
effect on interictal epileptiform EEG activity (as a surrogate marker for ictal
epileptiform activity), from which site and final parameters for chronic
stimulation will be determined. Upon removal of the clinically implanted
electrodes, a neurostimulator with sensing capabilities, Activa PC+S, will be
implanted and attached to two 4-lead intracranial electrode strips covering the
predefined stimulation site and the eloquent epileptogenic area.
During a data collection phase, stimulation-free data will then be collected to
train the seizure detection algorithm up to at least 50% sensitivity. When not
enough seizure data is collected, this phase will be extended. The next phase
is the REC2Stim phase, in which cortical stimulation is applied when seizure
activity is detected. When cortical closed-loop stimulation results in seizure
reduction in two consecutive months, a period of sham stimulation will follow.
The duration of which is dependent on the patient*s individual seizure
frequency. The REC2Stim phase can be extended if seizure frequency is not
decreased with at least 50%, and the principal investigator expects that this
seizure frequency can be reduced, and/or quality of life can be improved. In
that situation, sham stimulation will be delayed as well. Study participation
is one year. In case of delay of one or more phases, the participant is asked
whether he or she wants to continue participation or wants to end
participation. This question is repeated each year, unitl the patient decides
to end participation, the prinicpal investigator decides to end participation
in the study, or the Activa PC+S battery is depleted.
Study burden and risks
Participants have tried various anti-epileptic drugs and are not candidates for
epilepsy surgery. Therefore, they have no real therapeutic options left. Our
study is the only one focusing on these CLE patients. The study burden consists
of 2 extra monitoring days with tests; at least 15 post-implantation visits: 6
visits in the data collection phase (8 hours per visit), in which ictal data is
recorded, 9 visits in the REC2Stim phase in which intracranial EEG data is
streamed for one hour, and seizure detection algorithm and stimulus settings
may be adapted (9 x 2 hours); questionnaires to fill out before and after
implantation (2 x 45 minutes); and keeping a weekly diary to track number and
severity of seizures (48 x 10 minutes). Risks include disappointment or
depression when this treatment also proves ineffective; implant site infection
(2.5%); and intracranial hemorrhage (2.1%). When electrodes and/or
neurostimulator need to be explanted, there is the risk of the additional
surgery. These risks are estimated to be similar to other deep-brain
stimulations (in use for Parkinson*s disease and epilepsy). The potential
benefit may be large (seizure freedom without functional deficits).
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- at least 16 years of age
- potential central lobe epilepsy
- on average 2 or more seizures per day or ongoing EPC
- mentally and physically capable of giving informed consent
- minimally 3 anti-epileptic drugs been admitted without effect on seizure
frequency (refractory epilepsy)
Exclusion criteria
- coagulopathy, including use of anticoagulant or antiplatelet agents
- known allergy to the materials of the implant
- progressive neurological or systemic disease
- contra-indications to the presence of a chronically implanted device, such as
the need for repeated MRI, or concurrent infections
- any brain lesion that would place the patient at an elevated risk for bleeding
- any progressive brain disease, e.g. Rasmussen*s encephalitis or glioma
- presence of any active implanted metallic device, such as cardiac pace-maker,
vagal nerve or deep brain stimulator, cochlear implants, spinal cord stimulator
or metallic parts from non-medical origin
- presence of aneurysm clips
- SOZ outside eloquent cortex
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04158531 |
| CCMO | NL66795.041.18 |