
Martha J MorrellStanford University | SU · Department of Neurology and Neurological Sciences
Martha J Morrell
MD
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Publications (202)
Brain-responsive neurostimulation is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS System do not experience meaningful seizure reduction. Initial titration of RNS therapy is typically similar for all patients, raising the possibility that treatment response might be e...
This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy.
Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes m...
INTRODUCTION
Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation of the thalamus can be an effective treatment for LGS, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the tha...
Hundreds of 90-s iEEG records are typically captured from each NeuroPace RNS System patient between clinic visits. While these records provide invaluable information about the patient’s electrographic seizure and interictal activity patterns, manually classifying them into electrographic seizure/non-seizure activity, and manually identifying the se...
The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experien...
Finding electrophysiological features that are similar across patients with epilepsy may facilitate identifying treatment options for one patient that worked in patients with similar brain activity patterns. Three non-linear iEEG (intracranial electroencephalogram) embedding methods of finding similar cross-patient iEEG records in a large iEEG data...
Neuromodulation devices are approved in the United States for the treatment of movement disorders, epilepsy, pain, and depression, and are used off-label for other neurologic indications. By 2035, advances in our understanding of neuroanatomical networks and in the mechanism of action of stimulation, coupled with developments in material science, m...
Understanding consciousness is one of the most important and challenging questions in modern science. Existing theories have pursued single unifying mechanisms but do not succeed in explaining consciousness. Importantly, the neural circuits that distinguish messages that arrive from the outside world and attain consciousness have remained unknown....
Consciousness is not explained by a single mechanism, rather it involves multiple specialized neural systems overlapping in space and time. We hypothesize that synergistic, large-scale subcortical and cortical attention and signal processing networks encode conscious experiences. To identify brain activity in conscious perception without overt repo...
The objective of this study was to explore using ECoG spectrogram images for training reliable cross-patient electrographic seizure classifiers, and to characterize the classifiers’ test accuracy as a function of amount of training data. ECoG channels in ∼138,000 time-series ECoG records from 113 patients were converted to RGB spectrogram images. U...
Objective
To establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention.
Methods
Data were retrospectively analyzed from prospective clinical trials of a direct brain-responsive ne...
Objective
Understanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings.
Methods
In patients impl...
Introduction:
Epilepsy affects more than 1% of the US population, and over 30% of adults with epilepsy do not respond to antiseizure medications without life-impacting medication-related side effects. Resection of the seizure focus is not an option for many patients because it would cause unacceptable neurological or cognitive harm. For these pati...
Background:
Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a hu...
Objective
Prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.
Methods
Adults treated with brain-responsive neurostimulation within 2 year feasibility or randomized controlled trials enrolled into a long-term prospective open label trial (LTT)...
Objective
To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain‐responsive neurostimulator (RNS) system.
Methods
We retrospectively identified all pa...
Purpose:
To determine the feasibility of using epileptiform events detected by continuous electrocorticographic monitoring via a brain-responsive neurostimulation system to supplement patient-maintained seizure diaries.
Methods:
Data were retrospectively analyzed from a randomized controlled trial of brain-responsive neurostimulation (RNS® Syste...
Objectives
Describe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).
Methods
Clinical seizures from eight patients (mean follow-up of 10.1 years) were analyze...
Objectives
Find interictal electrocorticographic (ECoG) biomarkers of clinical outcomes in mesiotemporal lobe (MTL) epilepsy patients.
Methods
In the NeuroPace® RNS® System clinical trials with 256 patients, 20 MTL patients with the most reduction in clinical seizures at Year 7 compared to baseline (upper response quartile; −96.5% median change) a...
Controlled clinical trials in adults with medically intractable focal seizures treated with the RNS ® System demonstrate that closed-loop responsive neurostimulation to the seizure focus reduces the frequency of disabling seizures, is well tolerated, and is acceptably safe. Seizure reductions begin with initiation of treatment and continue over tim...
Introduction
Identifying electrographic features that differentiate patients with the most favorable response to epilepsy treatments will aid in discovering disease biomarkers and treatment endpoints, and could enhance patient selection. The RNS® System provides responsive direct-brain stimulation and is FDA approved for the treatment of medically...
Introduction
In a randomized controlled trial of the RNS® System, patients with mesial temporal lobe epilepsy (MTLE) had improvements in verbal memory, with maximal benefit in those with poorer baseline memory scores. However, improvements were not correlated with changes in clinical seizures. Here ECoG data were used to retrospectively assess the...
Objective:
The objective of this study was to explore whether chronic electrocorticographic (ECoG) data recorded by a responsive neurostimulation system could be used to assess clinical responses to antiepileptic drugs (AEDs).
Methods:
Antiepileptic drugs initiated and maintained for ≥3 months by patients participating in clinical trials of the...
Objective
Subacute and long-term electrocorticographic (ECoG) changes in ambulatory patients with depth and cortical strip electrodes were evaluated in order to determine the length of the implant effect.
Methods
ECoG records were assessed in patients with medically intractable epilepsy who had depth and/or strip leads implanted in order to be tre...
Background/aims:
The RNS® System utilizes a cranially implanted neurostimulator attached to leads placed at the seizure focus to provide brain responsive stimulation for the treatment of medically intractable partial onset epilepsy. Infection and erosion rates related to the cranial implant site were assessed overall and by neurostimulator procedu...
Objective:
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.
Methods:
Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neu...
Objective:
Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.
Methods:
Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPac...
Closed-loop, responsive focal brain stimulation provides a new treatment option for patients with refractory partial onset seizures who are not good candidates for potentially curative epilepsy surgery. The first responsive brain neurostimulator (RNS® System, NeuroPace), provides stimulation directly to the seizure focus when abnormal electrocortic...
Purpose: To characterize cyclic day-night patterns of electrocorticographic epileptiform activity (EA) in patients with focal onset seizures. Methods: Epileptiform events as defined by the physician (also termed more generally as "epileptiform activity" or EA) were recorded in 65 patients with partial onset (also referred to as "focal onset") seizu...
The Seventh International Workshop on Advances in Electrocorticography (ECoG) convened in Washington, DC, on November 13-14, 2014. Electrocorticography-basecl research continues to proliferate widely across basic science and clinical disciplines. The 2014 workshop highlighted advances in neurolinguistics, brain-computer interface, functional mappin...
Objective:
Responsive neurostimulation decreases the frequency of disabling seizures when used as an adjunctive therapy in patients with medically refractory partial-onset seizures. The effect of long-term responsive neurostimulation on neuropsychological performance has not yet been established.
Methods:
Neuropsychological data were collected f...
Objective:
Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide ad...
The primary efficacy and safety measures from a trial of responsive neurostimulation for focal epilepsy were previously published. In this report, the findings from the same study are presented for quality of life, which was a supportive analysis, and for mood, which was assessed as a secondary safety endpoint.
The study was a multicenter randomize...
The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.
All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic...
The RNS(®) System is the first commercially available device to provide closed-loop responsive brain stimulation. The system includes a cranially implanted neurostimulator that continually monitors the electrocorticogram through one or two depth and/or subdural cortical strip leads that are placed at the seizure focus. When abnormal electrographic...
Neurostimulation is now an established therapy for the treatment of movement disorders, pain, and epilepsy. While most neurostimulation systems available today provide stimulation in an open-loop manner (i.e., therapy is delivered according to preprogrammed settings and is unaffected by changes in the patient’s clinical symptoms or in the underlyin...
To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.
Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS...
Medical electrical lead systems and related methods are described. The lead systems may be configured to be at least partially implanted in neural tissue of a subject, such as a brain of a subject. Some variations of the lead systems may comprise a lead body, an electrode connected to the lead body, and a bioactive agent. The electrode and/or lead...
What are the risks and benefits of using divalproex sodium (Depakote) for treating seizures? Are there people who should avoid this drug?
This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy.
A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator conn...
Relationships between reproductive hormone levels, bone turnover marker levels, bone mineral density, and rates of bone loss were evaluated in premenopausal women with epilepsy taking enzyme-inducing antiepileptic drugs (EIAEDs: phenytoin or carbamazepine) or lamotrigine. Calciotropic and reproductive hormone levels, bone turnover marker levels, an...
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Previous studies have shown that closed-loop or responsive neurostimulation can abort induced or spontaneous epileptiform discharges.
To assess the effectiveness of a programmable cranially implanted closed-loop neurostimulation system in the control of seizures originating from an area relatively inaccessible by open craniotomy.
A patient with dru...
Epilepsy is a common chronic neurological disorder effecting 1 to 2% of the population. Despite advances in anti-epileptic drug therapy, epilepsy surgery, and vagus nerve stimulation, approximately 30% of patients continue to have seizures. Intracranial stimulation is currently under investigation as an adjunctive treatment to anti-epileptic medica...
This chapter explores the case of a woman who was diagnosed with cardiogenic syncope. Review of systems revealed episodes of mild light-headedness associated with menses. She recalled several nights of intense dreams, diaphoresis, and disrupted sleep over a year. General and neurological examinations were unremarkable. A brain magnetic resonance im...
To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.
Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) thera...
Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in premenopausal women with epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss wou...
Epilepsy is a common chronic neurological disorder affecting approximately 1-2% of the population. Despite the available treatment options (pharmacotherapy, surgery, and vagus nerve stimulation), a large percentage of patients continue to have seizures. With the success of deep brain stimulation for treatment of movement disorders, brain stimulatio...
OBJECTIVE: To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy. METHODS: Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotri...
NeuroPace has developed an experimental therapy for epilepsy that utilizes intracranial electrodes (subdural and depth) bipolar electrode pairs to monitor key epileptic network sites for the onset of seizure. When the beginning of a seizure is detected, a sequence of high frequency electric stimuli is delivered to one or more of the electrode pairs...
The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and...
The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and...
The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and...
Scheduled and responsive direct brain stimulation may be an effective and safe therapy for medically intractable epilepsy.
Scheduled stimulation (open loop) has been provided via electrodes implanted in thalamic nuclei, the cerebellum and the hippocampus using devices commercially available for treatment of tremor and Parkinson's disease. Small pil...