A Study to Evaluate Thalamic Stimulation to Prevent Impaired Consciousness in Epilepsy


About this study

The purpose of this study is to investigate the feasibility and safety of thalamic CL stimulation in restoring consciousness in epilepsy patients.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1. All patients will have evidence of mesial temporal seizures based on either

1. Intracranial EEG monitoring with mesial temporal lobe onset

2. or scalp EEG evidence of temporal lobe seizures and other evidence of mesial
temporal lobe epilepsy.

2. Subject's seizure focus, based upon clinical history, semiology,
electroencephalographic (EEG) findings, and/or neuroimaging, shall demonstrate
bilateral or unilateral mesial temporal lobe epilepsy, and subject shall not be good
candidate for surgical resection.

3. Focal epilepsy with disabling seizure counts mean of ≥ 2 per month. Disabling seizures
are those with significant negative impact on the patient's life, involving impaired
conscious awareness. Seizures counts will be based on patient's self-report. Note that
patient's typically have more disabling seizures than they are able to self-report,
and may also have additional non-disabling seizures in addition to the disabling
seizures required for enrolment.

i. Mean seizure count ≥ 2 per month is established initially for the preceding 6
months at time of Enrollment, using seizures reported by the patient and/or caregiver.
Seizures during EMU admissions are not included.

4. Drug resistance to at least two antiseizure medications (ASM) with adequate dose and

5. Subject is willing to remain on stable ASM from the Baseline phase through the end of
the Randomized CL Stimulation phase. Stable is defined as same medications, but dose
adjustments are allowed within accepted therapeutic ranges. Also, short-term
benzodiazepines allowed for acute seizure worsening as in prior studies.

6. Apart from epilepsy, subject must be medically and neurologically stable and must have
no other medical condition in the opinion of the treating physician that would
preclude the patient from participation. This could include conditions like severe
ischemic cardiac disease, progressive dementia or other disorders that could affect
surgical eligibility or compliance.

7. The local treating epilepsy center has recommended the patient for brain stimulation
therapy on clinical grounds and without reference to this protocol.

8. Age 18 to 75 years, inclusive, at time of consent.

9. Ability and willingness to provide informed consent and participate in the study

10. Subject can interpret and to respond, in accordance with the study protocol, to the
advisory indicators provided by the device. This includes the ability to recharge the

11. Subject has seizures that are distinct, stereotypical events that can be reliably
counted by the patient or caregiver.

12. Subject can reasonably be expected to maintain a seizure diary alone or with the
assistance of a competent individual.

13. Subject can complete regular office visits and telephone appointments in accordance
with the study protocol requirements.

14. A female subject must have a negative pregnancy test and if sexually active, must be
using a reliable form of birth control for the duration of the trial, be surgically
sterile, or be at least two years post-menopausal.

15. Subject has been informed of his or her eligibility for resective surgery as a
potential alternative to the study, if such surgery is a reasonable option.

16. Subject speaks and reads English.

17. Subject's anatomy will permit implantation of the Medtronic Investigational Summit
RC+S generator within 20 mm of the skin surface.

18. Subject is capable of completing the proposed neuropsychology evaluation and will
score no lower than 2 standard deviations below average on the Wechsler Adult
Intelligence Scale.

Exclusion Criteria:

1. Subject has a contraindication to magnetic resonance imaging.

2. Subject has a significant substance abuse history (alcohol, prescription, or illicit
medications) within the preceding two years with evidence of impact on daily function.

3. Subject participated in another drug or device trial within the preceding 30 days.

4. Demonstrates that they fulfill criteria on any of the three subscale of the SCID-5-PD
for borderline, antisocial, or narcissistic personality disorders and these criteria
are then corroborated by psychiatric interview, and that this would significantly
affect participation in the study.

5. Suicide attempt in the past year.

6. Arrest for assault or possession of drugs or weapons with intent to sell/distribute in
the past year.

7. Subject is implanted with pacemaker, implantable cardiac defibrillator, cardiac
management product, or a medical device that interferes with the RC+S device. This
includes, but is not limited to, direct brain neurostimulators, spinal cord
stimulators, vagus nerve stimulators (VNS), and cochlear implants. Patients with a
vagus nerve stimulator implanted but turned off through the duration of the study may
be enrolled, provided their clinical status has been stable for at least one month
with VNS turned off. Alternatively, patients with a VNS may have the previously
disabled VNS removed at time of surgery to implant the Medtronic RC+S.

8. Subject has confirmed active diagnosis of psychogenic or non-epileptic seizures.

9. Subject has confirmed diagnosis of primary generalized seizures.

10. Subject has experienced unprovoked status epilepticus in the preceding year.

11. Subject has had therapeutic surgery to treat epilepsy that may interfere with
electrode placement.

12. Subject has progressive neurological disorder or medical condition that would prevent
the participant to fully participate in the clinical trial.

13. Subject has severe chronic pulmonary disease or cardiac disease, local, systemic acute
or chronic infectious illness.

14. Subject is on anticoagulants and is unable to discontinue them peri-surgically, as
required by the neurosurgeon or Investigator.

15. Subject has significant platelet dysfunction from medical conditions or medications
(including, particularly, aspirin or sodium valproate). If platelet dysfunction is
suspected, subject can be enrolled only if a hematologist, the Investigator, and the
neurosurgeon judge it to be advisable.

16. Subject is ineligible for cranial surgery.

17. Subject scores equal to or below a full-scale intelligence quotient (FSIQ) of 70, as
measured by the Wechsler Adult Intelligence Scale.

18. Pregnancy.

19. Any condition or finding that in the judgement of the site PI significantly increases
risk or significantly reduces the likelihood of benefit from participation in the

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.


Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Gregory Worrell, M.D., Ph.D.

Closed for enrollment

Contact information:

Karla Crockett

(507) 538-4880


More information


  • Brain stimulation has emerged as an effective treatment for a wide range of neurological and psychiatric diseases. Parkinson's disease, epilepsy, and essential tremor have FDA indications for electrical brain stimulation using intracranially implanted electrodes. Interfacing implantable brain devices with local and cloud computing resources have the potential to improve electrical stimulation efficacy, disease tracking, and management. Epilepsy, in particular, is a neurological disease that might benefit from the integration of brain implants with off-the-body computing for tracking disease and therapy. Recent clinical trials have demonstrated seizure forecasting, seizure detection, and therapeutic electrical stimulation in patients with drug-resistant focal epilepsy. In this paper, we describe a next-generation epilepsy management system that integrates local handheld and cloud-computing resources wirelessly coupled to an implanted device with embedded payloads (sensors, intracranial EEG telemetry, electrical stimulation, classifiers, and control policy implementation). The handheld device and cloud computing resources can provide a seamless interface between patients and physicians, and realtime intracranial EEG can be used to classify brain state (wake/sleep, preseizure, and seizure), implement control policies for electrical stimulation, and track patient health. This system creates a flexible platform in which low demand analytics requiring fast response times are embedded in the implanted device and more complex algorithms are implemented in offthebody local and distributed cloud computing environments. The system enables tracking and management of epileptic neural networks operating over time scales ranging from milliseconds to months. Read More on PubMed
  • Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. Read More on PubMed
  • To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. Read More on PubMed
  • Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome and is often associated with pharmacoresistance. Patients with pharmacoresistant TLE may be candidates for epilepsy surgery, and anterior temporal lobectomy if indicated is the most effective known treatment and has the best chance of a seizure-free outcome. For many patients with TLE, epilepsy surgery is not an option, for example when the seizure onset zone co-localizes with eloquent brain function and cannot be resected, or the seizure onset zone is not well localized, or when seizures independently originate from both temporal lobes. For many of these patients, electrical stimulation is a viable treatment option, such as electrical stimulation of the hippocampus, or temporal neocortex, or thalamus. Animal and clinical studies in humans have demonstrated electrical stimulation is an effective and safe treatment. Moreover, successful application of responsive neurostimulation system in the treatment of temporal lobe epilepsy has been reported recently. This review is intended to provide a comprehensive review of the modern history of electrical stimulation of the hippocampus for the treatment of refractory medial temporal lobe epilepsy and discuss the anatomical basis, validity, side effects, stimulation paradigm and mechanism of hippocampus stimulation and the responsive electrical stimulation trials. Read More on PubMed
  • Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions. Read More on PubMed