Summary
Objective
To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE).
Methods
This ...randomized, single‐blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36‐month follow‐up.
Results
A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1‐sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English‐speaking, dominant‐hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients.
Significance
These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.
Objective
The RNS System is a direct brain‐responsive neurostimulation system that is US Food and Drug Administration–approved for adults with medically intractable focal onset seizures based on ...safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real‐world safety and effectiveness of the RNS System.
Methods
Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device‐related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow‐up.
Results
One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range IQR = 33%‐93%, n = 149) at 1 year, 75% (IQR = 50%‐94%, n = 93) at 2 years, 82% (IQR = 50%‐96%, n = 38) at ≥3 years, and 74% (IQR = 50%‐96%, n = 150) at last follow‐up (mean = 2.3 years). Thirty‐five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure‐free at last follow‐up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long‐lasting neurological consequences.
Significance
In this real‐world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.
Summary
Objective
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.
Methods
Randomized multicenter double‐blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow‐up.
Results
All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood.
Significance
Responsive stimulation to the seizure focus reduced the frequency of partial‐onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial‐onset seizures.
The hippocampus is the most common seizure focus in people. In the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models, but it is ...unknown whether this also holds true in humans. To address this question, we used immunofluorescence on control healthy hippocampus and surgical resections from mesial temporal lobe epilepsy (MTLE), plus neural stem-cell cultures and multi-electrode recordings of ex vivo hippocampal slices. We found that a longer duration of epilepsy is associated with a sharp decline in neuronal production and persistent numbers in astrogenesis. Further, immature neurons in MTLE are mostly inactive, and are not observed in cases with local epileptiform-like activity. However, immature astroglia are present in every MTLE case and their location and activity are dependent on epileptiform-like activity. Immature astroglia, rather than newborn neurons, therefore represent a potential target to continually modulate adult human neuronal hyperactivity.
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 patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3‐month follow‐up after MTL resection compared to seizure frequency 3 months before MTL resection.
Results
We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty‐five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow‐up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow‐up was 100% (mean: 94%; range: 50%‐100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure‐free at last follow‐up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%‐100%) at last follow‐up, with eight of fifteen seizure‐free. For those with more than 1 year of follow‐up (N = 21), 15 patients (71%) were seizure‐free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets.
Significance
Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.
Summary
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 additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.
Methods
Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded.
Results
Eighty‐two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0–376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording.
Significance
About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video‐EEG monitoring, and can contribute to treatment decisions.
Introduction The clinical results for the RNS System (NeuroPace, Mountain View, California, USA) closed-loop responsive neurostimulator for the treatment of medically intractable partial-onset ...seizures have been encouraging. The University of Southern California (USC) Neurorestoration Center and the Keck Hospital of USC have become the world's first institutions to implant an RNS System post U.S. Food and Drug Administration (FDA) approval. As one of the study centers, we review our experience with our group of patients who have been implanted with the RNS System. Methods A total of 40 surgeries by a single surgeon were performed on 10 patients (7 male and 3 female) with an average age of 39.2 years (24–66 years) and were followed for an average of 45 months (30–54 months). The average age at seizure onset was 14 years (birth–37 years) with an average of 4.7 (3–12) failed antiepileptic drugs. We reviewed the patients' charts for complications from the surgeries including infections requiring surgical intervention, hematomas, hardware failures, and death. Results Of the 40 surgeries, there were 10 initial implantations of the neurostimulator and leads, 24 neurostimulator replacements for expected end of neurostimulator service, 2 incision and drainage procedures (I & Ds) for soft tissue infection followed by 1 explantation and 1 reimplantation (same patient), and 2 revisions because of one lead that was damaged at the exit point between the skull and a titanium mesh and the second lead that was damaged at an acute bend over the skull (same patient). Eight of the patients had no complications and underwent an average of 2.7 neurostimulator replacements over 7 consecutive years to date. Each patient underwent routine postoperative computed tomography imaging of the brain, and none had any intracranial hematomas or misplaced leads requiring revision surgery. Finally, there were no deaths in our patient population. Conclusions Our experience with the NeuroPace RNS System over an average follow-up of 45 months suggests that the surgery and device are safe when placed by an experienced surgeon. Although there were no clinically significant hematomas or patient deaths, we did have 1 patient each with infection and lead damage at the point of exit from the skull. We compare the results of this study with other neuromodulation procedures for epilepsy to evaluate the safety and complications associated with the RNS System. Our initial experience suggests that the RNS System can be readily incorporated into an active epilepsy surgical center.
There is great concern for cognitive function after resective temporal lobe surgery for drug-resistant epilepsy. However, few studies have investigated postoperative anatomical changes, and the ...downstream effects of surgery are poorly understood. This study investigated volumetric changes after resective surgery and vagus nerve stimulation (VNS) for epilepsy.
Preoperative and latest postoperative (mean, 28 months) structural T1 magnetic resonance imaging scans were retrospectively obtained for 43 patients: 27 temporal lobe resections (TLRs), 6 extratemporal lobe resections, and 10 VNS, undergoing surgery for drug-resistant epilepsy between 2012 and 2017. Automated volumetric analyses of predefined cortical gray matter and subcortical structures were performed. Preoperative and postoperative volumes were compared, and the effects of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on volumetric changes were analyzed.
After TLRs, there were reductions in contralateral hemispheric gray matter, temporal lobe, entorhinal cortex, parahippocampal, superior temporal, middle temporal, inferior temporal (P = 0.02), lingual, fusiform, precentral, paracentral, postcentral, pericalcarine gyri, and ipsilateral superior parietal gyrus. After VNS, there was bilateral atrophy in the thalamus, putamen, cerebellum, rostral anterior cingulate, posterior cingulate, medial orbitofrontal, paracentral, fusiform, and transverse temporal gyri. There was a significant effect of surgery type but no effect of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on contralateral hippocampal gray matter change.
This is the first study to demonstrate volumetric decreases in temporal and connected regions after TLRs and VNS. These results provide interesting insight into functional network changes.
The objective of this study was to investigate the effect of epilepsy surgery on depression, anxiety, and quality of life (QOL) in a Hispanic, primarily immigrant, Spanish-speaking population with ...intractable epilepsy (IE).
Patients with IE from a comprehensive epilepsy treatment center in an urban, public healthcare setting who underwent resective brain surgery between 2008 and 2014 (N=47) and completed presurgical and postsurgical neuropsychological evaluation were retrospectively identified. Presurgical and 1-year postsurgical Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and QOLIE-31 ratings were analyzed as postsurgical outcome measures. One-tailed paired sample t-tests were used to evaluate whether scores improved postoperatively. Established severity level classifications of depression and anxiety (i.e., minimal, mild, moderate, or severe) were used to analyze changes in occurrence of depression and anxiety.
Medium to large improvements on the BDI-II and most QOLIE-31 subscales, with a smaller effect on the BAI and remaining QOLIE-31 subscales, were noted 1-year postsurgery. Levels of depression and anxiety were significantly reduced 1-year postsurgery. Depression, anxiety, and QOL improvements were robust and unaffected by gender, levels of education, or hemisphere of surgery.
This study supports the positive benefits of epilepsy surgery on depression, anxiety, and QOL in Hispanic, primarily undocumented immigrant, Spanish-speaking people with epilepsy (PWE) in the US. These results are useful for educating this particular population about the possible benefits of surgery for IE and can enhance presurgical counseling.
•Mood, anxiety, and QOL of underserved US Hispanics improve 1-year after epilepsy surgery.•This unique population's surgical outcomes are consistent with other populations.•Mood, anxiety, and QOL improved across 1-year ILAE seizure outcome groups.•These results are useful for educating Hispanics about benefits of epilepsy surgery.•Culturally responsive care for underserved, immigrant, and US Hispanics is presented.
•We report methods to prepare hippocampal slices from temporal lobectomy subjects.•This is the first application of using planar MEA to study human hippocampal tissue.•A portable system was designed ...and fabricated to transport human brain tissue.•A novel approach to induce epileptiform in human epileptogenic hippocampal slices is described.•Inter-ictal like activity was consistently observed in DG, CA1, and SUB subregions.
Temporal lobe epilepsy is a neurological condition marked by seizures, typically accompanied by large amplitude synchronous electrophysiological discharges, affecting a variety of mental and physical functions. The neurobiological mechanisms responsible for the onset and termination of seizures are still unclear. While pharmacological therapies can suppress the symptoms of seizures, typically 30% of patients do not respond well to drug control. Unilateral temporal lobectomy, a procedure in which a substantial part of the hippocampal formation and surrounding tissue is removed, is a common surgical treatment for medically refractory epilepsy. In this study, we have developed an in vitro model of epilepsy using human hippocampal slices resected from patients suffering from intractable mesial temporal lobe epilepsy. We show that using a planar multi-electrode array system, spatio-temporal inter-ictal like activity can be consistently recorded in high-potassium (8mM), low-magnesium (0.25mM) artificial cerebral spinal fluid with 4-aminopyridine (100μM) added. The induced epileptiform discharges can be recorded in different subregions of the hippocampus, including dentate, CA1 and subiculum. This new paradigm will allow the study of seizure generation in different subregions of hippocampus simultaneously, as well as propagation of seizure activity throughout the intrinsic circuitry of hippocampus. This experimental model also should provide insights into seizure control and prevention, while providing a platform to develop novel, anti-seizure therapeutics.
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