The goal is to provide a novel therapeutic option for temporal lobe epilepsy patients when focal impaired awareness seizures cannot be stopped by medications, surgical or laser ablation, or by neurostimulation. The goal is restore consciousness when seizures cannot be stopped. If successful, addition of bilateral thalamic stimulation to existing responsive neurostimulation to rescue consciousness would greatly alter clinical practice and patient outcomes. Importantly, previous approaches aim to stop seizures, whereas this study aims to use thalamic stimulation to improve a major negative consequence when seizures cannot be stopped. The potential impact extends beyond temporal lobe epilepsy to other seizure types, and may also extend more broadly to inform treatment of other brain disorders associated with impaired consciousness and cognition.
Impaired consciousness during seizures has a major negative impact on quality of life for people with epilepsy. Consequences include risk of motor vehicle accidents, drowning, poor work and school performance, and social stigmatization. Impaired ictal/postictal arousal may also compromise breathing leading to sudden unexpected death in epilepsy. Although the primary goal of epilepsy care is to stop seizures, restoring conscious awareness in patients whose seizures cannot be stopped (by medications, surgery or deep brain stimulation) could significantly improve outcome. Disorders of consciousness other than epilepsy have long been known to arise from dysfunction of subcortical-cortical arousal circuits. Deep brain stimulation (DBS) of the thalamic intralaminar central lateral nuclei (CL) is a promising approach to restore conscious arousal currently being trialed for chronic disorders of consciousness. Recent neuroimaging and EEG studies have shown that transient impaired consciousness in temporal lobe epilepsy (TLE) seizures also depends on subcortical-cortical arousal including thalamic CL. Translational studies from this research group further demonstrate depressed CL function in limbic seizures, and most importantly that thalamic CL stimulation has the potential to restore physiological and behavioral arousal in the ictal and postictal periods. DBS treatment of epilepsy has advanced rapidly with FDA approval of responsive neurostimulation (RNS, NeuroPace) and thalamic anterior nucleus stimulation (Medtronic). Investigational devices such as the Medtronic Summit RC+S provide a unique opportunity for responsive stimulation of up to four separate brain regions, enabling conventional sites such as hippocampus (HC) to be combined with innovative targets such as thalamic CL. Meanwhile, collaborators Mayo Clinic have developed the Epilepsy Personal Assistant Device (EPAD), a custom application running on a hand-held device with bi-directional communication with the RC+S. The EPAD will enable cloud-based data storage, seizure diaries, and automatic behavioral tests. Therefore, the goal is to develop and pilot test the feasibility and safety of bilateral thalamic CL stimulation using RC+S to restore conscious arousal in TLE seizures which are not stopped by conventional responsive neurostimulation, offering hope to greatly improve quality of life in these patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
5
Stimulation of the bilateral thalamic CL is a promising approach in human patients to improve conscious arousal. To restore conscious arousal by stimulation of the thalamic intralaminar CL it is necessary to provide bilateral stimulation, placing one lead in each thalamus. Bilateral thalamic CL stimulation was shown previously to improve human conscious arousal and is based on existing research in patients with disorders of consciousness.
The hippocampus has been a target for brain stimulation for seizure reduction in epilepsy. While the efficacy of HC stimulation varies considerably among different studies, the surgical procedure and therapeutic electrical stimulation are well tolerated by patients, with few peri-operative complications being reported, and histopathologic analysis not revealing a difference between stimulated and non-stimulated hippocampal tissue (Han et al. 2014)
Yale New Haven Hospital
New Haven, Connecticut, United States
Mayo Clinic
Rochester, Minnesota, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Change in Conscious Awareness
Evaluate levels of conscious awareness during and following seizures, based on a behavioral responsiveness scale. Behavioral responsiveness is delivered on a tablet device automatically when a seizure is identified by the neurostimulator device. Automatic Responsiveness Testing in Epilepsy has a score range of 0 to 18, where 0 is not consciousness and/or unable to interact appropriately to commands and 18 is conscious, aware, and able to interact appropriately to commands. This is measured at scheduled in weekly intervals prior to implant and continuously over the 45 months of participation that occur post-implant.
Time frame: Up to 45 months
Change in Seizure Severity
Evaluate changes seizure severity with the Liverpool Seizure Severity Questionnaire. Questionnaires will be given to patients to complete during in-person visits to evaluate changes in reported seizure frequency, which will also be compared to the objective seizure count from the Medtronic Summit RC+S device post-implant. The Liverpool Seizure Severity Scale 2.0 questionnaire produces a single unit-weighted scale that measures severity of the most severe seizures the patient experienced during the recall period. Score ranges are from 0 to 100, where 0 is the patient reports no seizures whereas 100 indicates frequent seizures with severe symptomology, including headaches, confusion, and delays in returning to tasks. Measured at each in-person visit from Baseline to End of Study (13 times over 45 months).
Time frame: Up to 45 months
Change in Quality of Life
Evaluate changes quality of life periodically with epilepsy-specific standardized assessment tools. Questionnaire will be given to patients to complete at in-person visits as to evaluate changes in quality of life. Quality of Life in Epilepsy Inventory is converted to a t-score range of 11 to 73, where 11 is a low quality of life with limited independence, low cognitive function, and significant seizure worry whereas a score of 73 indicates high levels of satisfaction in their health, minimal seizure worry, and high social function. Measured at each in-person visit from Baseline to End of Study (13 times over 45 months).
Time frame: Up to 45 months
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