Diffusion Tensor Orientation as a Microstructural MRI Marker of Mossy Fiber Sprouting After TBI in Rats.

Diffusion tensor imaging (DTI) metrics are highly sensitive to microstructural brain alterations and are potentially useful imaging biomarkers for underlying neuropathologic changes after experimental and human traumatic brain injury (TBI). As potential imaging biomarkers require direct correlation with neuropathologic alterations for validation and interpretation, this study systematically examined neuropathologic abnormalities underlying alterations in DTI metrics in the hippocampus and cortex following controlled cortical impact (CCI) in rats. Ex vivo DTI metrics were directly compared with a comprehensive histologic battery for neurodegeneration, microgliosis, astrocytosis, and mossy fiber sprouting by Timm histochemistry at carefully matched locations immediately, 48 hours, and 4 weeks after injury. DTI abnormalities corresponded to spatially overlapping but temporally distinct neuropathologic alterations representing an aggregate measure of dynamic tissue damage and reorganization. Prominent DTI alterations of were observed for both the immediate and acute intervals after injury and associated with neurodegeneration and inflammation. In the chronic period, diffusion tensor orientation in the hilus of the dentate gyrus became prominently abnormal and was identified as a reliable structural biomarker for mossy fiber sprouting after CCI in rats, suggesting potential application as a biomarker to follow secondary progression in experimental and human TBI.

Comparison of Language and Memory Lateralization by Functional MRI and Wada Test in Epilepsy.

The intracarotid sodium amobarbital procedure (ISAP or Wada test) lateralizes cerebral functions to the cerebral hemispheres preoperatively. Functional magnetic resonance imaging (fMRI) is increasingly used to characterize preoperative language and memory lateralization. In this study, concordance of fMRI with Wada was examined in patients with medically intractable seizures. The relationship of the distance between the epileptogenic focus to functional activation area with patients' post-operative deficits in language was also analyzed. 27 epilepsy patients with preoperative fMRI and Wada data were analyzed using established fMRI paradigms for language and memory. Activation of Broca's and Wernicke's areas were measured in three dimensions. Language and memory lateralization were determined, and standard neuropsychiatry Wada test procedures were used for comparison. The shortest distance between a language area to the border of surgical focus (LAD) was also measured and compared with postoperative language deficits. Our study found that concordance between fMRI and Wada testing was 0.41 (Kappa's 'fair to good' concordance) for language dominance and 0.1 (Kappa's 'poor' concordance) for memory. No significant correlation was found between LAD and post-op language deficit (p=0.439). A correlation was found between LAD and post-op memory deficit (p=0.049; the further distance from surgical lesion to language area is associated with less post-operative memory loss). Females demonstrated significantly increased postoperative seizure improvement (Fisher's p-value=0.0296; female=8; male=6). A significant association between handedness (right-handed subjects) and postoperative seizure improvement was found (p=0.02) as well as a significant trend for interaction of gender and handedness on postoperative seizure improvement (p=0.09). Overall, our results demonstrate fMRI as a useful preoperative adjunct to Wada testing for language lateralization in patients with medically intractable seizures.

Validity testing in veterans with epileptic seizures and psychogenic nonepileptic seizures.

OBJECTIVE: Identification of clinically meaningful subgroups among patients with psychogenic nonepileptic seizures (PNES) or epileptic seizures (ES) is of potential value for assessing prognosis and predicting therapeutic response. Invalid performance on validity tests has been associated with noncredible complaints and worse cognitive test scores, and may be one such classification criteria. We studied invalid performance in Veterans with PNES or ES, and the association of invalid performance with cognitive test scores and subjective complaints. METHODS: Patients were consecutive admissions to three veterans affairs (VA) epilepsy monitoring units. Evaluations included two validity tests: the Test of Memory Malingering (TOMM); and the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) over-reporting validity scales. We compared the frequency of invalid performance on the TOMM or MMPI-2-RF in patients diagnosed with PNES vs. ES. We evaluated the association of invalid performance with scores on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), and four subjective symptom measures including the Beck Depression Inventory-II, and Quality of Life in Epilepsy-31. RESULTS: Invalid TOMM performance was found in 25.3% of Veterans diagnosed with PNES and 10.8% of those with ES (p = .03). Invalid reporting on the MMPI-2-RF was found in 35.9% of the PNES group vs. 15.3% of the ES group (p = .01). Effects of valid vs. invalid reporting on external measures were similar for ES and PNES groups. Patients with invalid vs. valid TOMM performance had lower scores on the RBANS (p < .001). Patients with invalid performance had greater complaints on all subjective measures, with largest effect sizes for the MMPI-2-RF validity scales (p < .001). SIGNIFICANCE: In Veterans admitted for evaluation of poorly controlled seizures, invalid performance on validity tests was not uncommon. Cognitive test results and subjective reports from patients with invalid performance may not be credible. These observations have implications for the analysis of clinical trials, where primary and secondary outcomes often rely on self-report measures.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To 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 in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

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.

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings.

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 analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics. RESULTS: Mean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus. CONCLUSIONS: RNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation. SIGNIFICANCE: Chronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.

Health-related quality of life in Veterans with epileptic and psychogenic nonepileptic seizures.

RATIONALE: Health-related quality of life (HRQoL) is compromised in civilians with epileptic seizures (ES) or psychogenic nonepileptic seizures (PNES). U.S. Veterans are a distinct patient group with regard to gender, age, and background. We studied HRQoL in Veterans and asked the following: (1) Is there a difference in HRQoL in Veterans with ES vs. PNES?; (2) What factors influence HRQoL in each group?; (3) What factors influenced the difference between seizure groups? METHODS: We studied consecutive Veterans entering the epilepsy monitoring units (EMUs) of three VA Epilepsy Centers of Excellence. Patients underwent continuous video-EEG monitoring. Seizure diagnoses followed established criteria. Health-related quality of life was measured with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Evaluations included the Structured Clinical Interview for Diagnostic and Statistical Manual-IV (DSM IV), the posttraumatic stress disorder (PTSD) Checklist (PCL), the Beck Depression Inventory II (BDI-II), and the Minnesota Multiphasic Personality Inventory-2 Restructured form (MMPI-2RF). Between-group differences were tested with Wilcoxon tests. Nested regression analysis was used to evaluate the influence of demographic, social, military, seizure-related, and psychological factors on QOLIE-31 scores. RESULTS: The median QOLIE-31 total score was 14 points lower in Veterans with PNES vs. ES (p < 0.001; Cohen's d = 0.73). Within each seizure group, psychological factors accounted for ≥50% of the variance in QOLIE scores while combined demographic, social, and seizure-related factors accounted for 18% (group with ES) and 7% (PNES). Psychological measures, particularly PCL and the BDI-II scores, accounted for all of the difference in QOLIE-31 total scores between Veterans with ES and those with PNES. CONCLUSIONS: Health-related quality of life as measured by the QOLIE-31 is worse in Veterans with PNES as compared with those with ES. Psychological factors account for the most of the variance in QOLIE-31 scores regardless of seizure type and also account for the difference between groups with PNES and ES. Demographic, military, social, and seizure-related factors have minimal influence on HRQoL. These results in U.S. Veterans are similar to those found in civilians despite differences in patient age, gender, and background.

2-Deoxy-d-glucose reduces epileptiform activity by presynaptic mechanisms.

2-Deoxy-d-glucose (2DG), a glucose analog that inhibits glycolysis, has acute and chronic antiepileptic effects. We evaluated 2DG's acute effects on synaptic and membrane properties of CA3 pyramidal neurons in vitro. 2DG (10 mM) had no effects on spontaneously occurring postsynaptic currents (PSCs) in 3.5 mM extracellular potassium concentration ([K+]o). In 7.5 mM [K+]o, 2DG significantly reduced the frequency of epileptiform bursting and the charge carried by postsynaptic currents (PSCs) with a greater effect on inward excitatory compared with outward inhibitory charge (71% vs. 40%). In 7.5 mM [K+]o and bicuculline, 2DG reduced significantly the excitatory charge by 67% and decreased the frequency but not amplitude of excitatory PSCs between bursts. In 7.5 mM [K+]o, 2DG reduced pharmacologically isolated inhibitory PSC frequency without a change in amplitude. The frequency but not amplitude of inward miniature PSCs was reduced when 2DG was applied in 7.5 mM [K+]o before bath application of TTX, but there was no effect when 2DG was applied after TTX, indicating a use-dependent uptake of 2DG was required for its actions at a presynaptic locus. 2DG did not alter membrane properties of CA3 neurons except for reducing the slow afterhyperpolarization in 3.5 but not 7.5 mM [K+]o. The reduction in frequency of spontaneous and inward miniature PSCs in elevated [K+]o indicates a presynaptic mechanism of action. 2DG effects required use-dependent uptake and suggest an important role for glycolysis in neuronal metabolism and energetics in states of high neural activity as occur during abnormal network synchronization and seizures. NEW & NOTEWORTHY 2-Deoxy-d-glucose (2DG) is a glycolytic inhibitor and suppresses epileptiform activity acutely and has chronic antiepileptic effects. The mechanisms of the acute effects are not well delineated. In this study, we show 2DG suppressed abnormal network epileptiform activity without effecting normal synaptic network activity or membrane properties. The effects appear to be use dependent and have a presynaptic locus of action. Inhibition of glycolysis is a novel presynaptic mechanism to limit abnormal neuronal network activity and seizures.

Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats.

We hypothesized that the acute response to traumatic brain injury (TBI) shares mechanisms with brain plasticity in the kindling model. Utilizing two unique, complementary strains of inbred rats, selected to be either susceptible or resistant to seizure-induced plasticity evoked by kindling of the perforant path, we examined acute electrophysiological alterations and differences in brain-derived neurotrophic factor (BDNF) protein concentrations after a moderate-to-severe brain injury. At baseline, limited strain-dependent differences in acute electrophysiological activity were found, and no differences in BDNF. Following injury, pronounced strain-dependent differences in electrophysiologic activity were noted at 0.5 min. However, the divergence is transient, with diminished differences at 5 min after injury and no differences at 10 and 15 min after injury. Strain-specific differences in BDNF protein concentration were noted 4 h after injury. A simple risk score model generated by machine learning and based solely on post-injury electrophysiologic activity at the 0.5-min timepoint distinguished perforant path kindling susceptible (PPKS) rats from non-plasticity-susceptible strains. The findings demonstrate that genetic background which affects brain circuit plasticity also affects acute response to TBI. An improved understanding of the effect of genetic background on the cellular, molecular, and circuit plasticity mechanisms activated in response to TBI and their timecourse is key in developing much-needed novel therapeutic approaches.

Psychiatric comorbidity and traumatic brain injury attribution in patients with psychogenic nonepileptic or epileptic seizures: A multicenter study of US veterans.

OBJECTIVE: To determine the frequency and severity of psychiatric disorders and attribution of seizures to traumatic brain injury (TBI) in veterans with verified psychogenic nonepileptic seizures (PNES) versus epileptic seizures (ES). METHODS: We studied 333 consecutive admissions to the monitoring units of three Veterans Administration epilepsy centers. All patients underwent continuous video-electroencephalographic recording to define definite PNES or ES. Evaluations included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, PTSD Checklist, Beck Depression Inventory II, and Patient Seizure Etiology Questionnaire. Interviews and questionnaires were completed prior to final seizure type diagnosis and patient debriefing. The primary outcome measure was a comparison of Axis I psychiatric diagnoses in patients diagnosed with PNES versus ES. RESULTS: A total of 81 patients were diagnosed with PNES, and 70 with ES. PTSD was the most frequent Axis I diagnosis in veterans with PNES (64%, vs 13% of those with ES; P < 0.001). Posttraumatic stress disorder (PTSD) was common regardless of deployment to a war theater or combat exposure. Mood, substance abuse, and anxiety disorders were also more common in the PNES group. TBI was cited as a likely cause of seizures by 47% of veterans with PNES versus 25% of those with ES (P = 0.01). PTSD and attribution of seizures to TBI were found in 30% of veterans with PNES versus 3% of those with ES (P < 0.001). SIGNIFICANCE: In veterans referred for inpatient seizure evaluation, PTSD was strongly associated with a diagnosis of PNES versus ES. The association of PNES with PTSD, attribution of seizures to TBI, or both, may prompt early consideration of PNES.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

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 neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

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, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Epilepsy Among Iraq and Afghanistan War Veterans - United States, 2002-2015.

The age-adjusted prevalence of seizure disorder in United States veterans deployed in Iraq and Afghanistan conflicts (IAV) is 6.1 per 1,000 persons (1), compared with 7.1 to 10 per 1,000 persons in the general population (2,3). Persons with epilepsy are at risk of excess mortality in part because of comorbidity (4). Although patterns of comorbidity have been associated with mortality in IAV (5), the unique contribution of epilepsy to excess mortality in IAV is unknown. A cohort study was developed using inpatient, outpatient, and pharmacy data from the U.S. Department of Veterans Affairs, Veterans Health Administration (VA) to identify epilepsy, demographic characteristics, and baseline comorbidity for IAV who received VA care in 2010 and 2011. The VA's vital status records were used to identify 5-year mortality (2011-2015). The unadjusted Kaplan-Meier estimator and adjusted proportional hazards regression models tested the hypothesis that excess mortality is associated with epilepsy. IAV with epilepsy were more likely than those without epilepsy to have mental and physical comorbidity, and significantly higher mortality, even after controlling for demographic characteristics and other comorbid conditions (adjusted hazard ratio = 2.6; 95% confidence interval [CI] 2.1-3.2). IAV with epilepsy could benefit from evidence-based chronic disease self-management programs to reduce physical and psychiatric comorbidity, and linkages to VA clinical and other community health and social service providers.

Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients.

Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network.

Attributing seizures to TBI: Validation of a brief patient questionnaire.

PURPOSE: Traumatic brain injury (TBI) is an important cause of epilepsy and has also been associated with psychogenic nonepileptic seizures (PNES). We designed a brief questionnaire assessing patient beliefs regarding TBI as the cause of their seizures (Patient Seizure Etiology Questionnaire; PSEQ). This study reports content validity for the PSEQ. METHODS: Ninety Veterans undergoing comprehensive evaluation at 3 VA epilepsy centers completed the PSEQ, a series of questions regarding possible causes for their seizures, including TBI. The PSEQ was scored as YES vs. NO for TBI as the proposed cause of seizures. For each patient, two expert reviewers independently completed a structured chart review to determine whether TBI was the proposed cause of seizures (n=180 reviews). Kappa statistic was used to assess agreement between the PSEQ and each chart review and between the PSEQ and combined chart reviews where both reviewers agreed on a TBI seizure etiology. RESULTS: The PSEQ scored higher overall rates for a TBI seizure etiology than did expert chart reviews (40% vs. 28%; p<0.001). The PSEQ agreed with 82% of 180 independent chart reviews (sensitivity 88%; specificity 79%). Kappa statistic for agreement was 0.60. The two reviewers agreed on a probable TBI seizure etiology for 83% of chart reviews. The PSEQ sensitivity increased to 100% when both reviewers were in agreement. CONCLUSION: The PSEQ provides a direct, standardized measure of patient beliefs regarding TBI as the cause of their seizures and has moderate-substantial agreement with expert chart reviews.

Providing Quality Epilepsy Care for Veterans.

Quality epilepsy care depends on balancing seizure control with medication adverse effects and on understanding a patient's medical history and anxieties related to the illness.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

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.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: 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 patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

A Case of Celiac Disease, Epilepsy, and Cerebral Calcifications With Temporal Lobe Epilepsy.

This is a case report of a 55-year-old man with medication refractory right temporal lobe epilepsy since adolescence. He was found to have bilateral posterior cerebral calcifications on routine head computed tomography with confirmation on magnetic resonance imaging. He also had elevated antibody markers for celiac disease. He was diagnosed with the rare, but well-described syndrome of celiac disease, epilepsy, and cerebral calcifications (CEC). He failed a brief trial of gluten-free diet and went on to have a right temporal lobectomy with sustained freedom from disabling seizures. This case is an example of the growing recognition of neurologic disorders associated with celiac disease. It also provides an example of the characteristic radiographic sign associated with CEC.