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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 χ 2 )., 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., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: Due to the complex pharmacokinetic profiles of phenytoin (PHT) and fosphenytoin (FOS), achieving sustained, targeted serum PHT levels in the first day of use is challenging., Methods: A population based approach was used to analyze total serum PHT (tPHT) level within 2-24h of PHT/FOS loading with or without supplementary maintenance or additional loading doses among PHT-naïve patients in the acute hospital setting. Adequate tPHT serum level was defined as ≥20μg/mL., Results: Among 494 patients with 545 tPHT serum levels obtained in the first 2-24h after the loading dose (LD), tPHT serum levels of either

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., (© 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine whether seizure semiology is reliable in localizing and distinguishing seizures at 2 independent brain foci in the same patient., Design: Two masked reviewers localized seizures from 2 foci by their clinical semiology and intracranial electroencephalograms (EEGs)., Setting: Epilepsy monitoring unit of referral comprehensive epilepsy program., Patients: Seventeen consecutive patients (51 seizures) with sufficient video and intracranial EEG data were identified by reviewing medical records of 366 patients older than 10 years., Main Outcome Measures: The primary outcome measures were interobserver agreement between the 2 masked reviewers; the proportion of seizures localized by semiology; the proportion of localized seizures concordant with intracranial EEG localization; and comparison between concordant and nonconcordant seizures in latency of intracranial EEG seizure spread., Results: Interobserver agreement was 41% (κ score, 0.16). Only 30 of 51 seizures (59%) were localized by seizure semiology. The focus localized by semiology was concordant with the location of intracranial EEG seizure onset in 16 of 30 seizures (53%). No significant difference was observed between concordant and nonconcordant seizures in relation to the speed with which the EEG discharge spread from the location of seizure onset to another lobar region (P = .09, Wilcoxon rank sum test)., Conclusion: Clinical seizure semiology is not as useful as intracranial EEG in localizing seizure onset in patients with dual seizure foci.

Objective: Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients., Methods: Three separate experiments used healthy adults treated with lamotrigine (LTG) and topiramate (TPM), adults with epilepsy on LTG or TPM, and patients with idiopathic Parkinson's disease. Correlations were calculated for change scores on and off drugs in the first two experiments and for the single assessment in Experiment 3., Results: Across all three experiments, significant correlations were more frequent (chi(2)=259, P < or = 0.000) for mood versus subjective cognitive perception (59%) compared with subjective versus objective cognition (2%) and mood versus objective cognitive performance (2%)., Conclusions: Subjective perception of cognitive effects is related more to mood than objective performance. Clinicians should be aware of this relationship when assessing patients' cognitive complaints.

Background: Psychiatric disorders may occur in patients with intractable partial epilepsy after surgical treatment. Previous reports attributed the presence of psychological adverse events to specific pathological entities such as dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. The rationale for the present study is to evaluate the importance of the surgical pathology in individuals undergoing epilepsy surgery., Methods: The patients were separated into three groups based on the surgical pathology: group I ganglioglioma (N=25), group II DNETs (N=25), and group III mesial temporal sclerosis (N=25). Thirteen of the 75 patients (17.3%) had a preexisting psychiatric disorder. The most common preoperative psychiatric diagnosis was depression (N=4). Sixty-three of the lesions (84%) were restricted to the temporal lobe. The operative strategy included resection of the lesion and epileptogenic cortex. Sixty-two of the 75 patients (83%) were rendered seizure-free., Results: Eight of the 75 patients (10.7%) had an acquired psychiatric illness following surgical treatment. A mood disorder developed in three patients after surgery. No statistical difference emerged in preoperative psychiatric co-morbidity (no group difference; p=1.0) or in newly diagnosed postoperative psychiatric disease (group I vs. II, p=0.67; group I vs. III, p=1.0; and group II vs. III, p=0.67) within the three surgical pathology groups., Conclusion: This study indicates that the presence of psychiatric disease before and after surgery for intractable partial epilepsy, predominantly of temporal lobe origin, was independent of the pathological findings.

Object: The aim of this study was to determine whether ictal single-photon emission computed tomography (SPECT) is useful in localizing the site of seizure onset in patients in whom surgery for intractable epilepsy failed and who are being considered for repeated surgery., Methods: Subtraction ictal SPECT coregistered to magnetic resonance imaging (SISCOM) studies were retrospectively analyzed in 58 patients who were being evaluated for possible repeated resection for intractable partial epilepsy between January 1, 1996, and October 31, 1999. All patients had persistent seizures subsequent to an initial resection and underwent another excision. The SISCOM-demonstrated abnormalities were classified as concordant, discordant, or indeterminate, compared with the localization of the epileptogenic zone revealed on video electroencephalography monitoring. The ability of SISCOM to predict operative outcome was also determined in patients who had undergone repeated surgical procedures. The SISCOM studies revealed a localized hyperperfused alteration in 46 (79%) of 58 patients. Forty-one (89%) of these 46 patients had a SISCOM-demonstrated alteration in the hemisphere of the previous epilepsy surgery. Imaging changes in 33 (72%) of the 46 patients were at the site of the previous focal cortical resection. Eight (17%) of the 46 had SISCOM-demonstrated abnormalities remote from the lobe in which surgery had been performed but in the ipsilateral hemisphere. The hyperperfusion focus was in the contralateral hemisphere in the remaining five patients (11%). The site of the epileptogenic zone was concordant with the SISCOM focus in 32 (70%) of 46 patients. Twenty-six patients underwent repeated resection and were followed up for a mean of 44 months thereafter; 11 of these patients (42%) had a significant reduction in seizure tendency. Only five patients (19%) were seizure free. Ten (50%) of 20 patients with a concordant SISCOM focus compared with none (0%) of three patients with a discordant focus had a favorable surgical outcome (p = 0.23)., Conclusions: The SISCOM method might be useful in the evaluation of, and the surgical planning for, patients with intractable partial epilepsy in whom previous resective treatment has failed and who are being considered for reoperation.

Purpose: To compare seizure frequency reported in the clinic with time to first diagnostic event during video-EEG monitoring. The effect of the artificial environment of the monitoring unit on self-reported seizure frequency was explored., Methods: The 155 consecutive patients were seen in the Washington University Epilepsy Center and subsequently underwent video-EEG monitoring during 2001. Of these, 112 had a diagnostic event during monitoring; 31 left without having a definite event; and 12 could not provide an estimate of seizure frequency in the clinic. The time to first event was compared with self-reported seizure frequency. The patients were then divided into three equal groups (tertiles) based on mean seizure frequency, and time to first seizure was compared between groups. Then the numbers of patients staying >7 days without ever having an event were compared between the low and high seizure-frequency groups. Finally, Kaplan-Meier survival curves were calculated., Results: No correlation was found between self-reported seizure rate and time to diagnostic event (r= 0.18; p = 0.06). Time to first event was 2.8 days in the low seizure-frequency group (mean, 2.2/month), 2.1 days in the medium (mean, 8.8/month), and 2.1 days in the high (mean, 24.1/month) groups, which were not significantly different (p = 0.19). Of patients in the low-frequency group, 79% had an event within 7 days., Conclusions: In the artificial environment of the monitoring unit, self-reported outpatient seizure frequency is not an accurate predictor of duration of video-EEG monitoring required to make a definitive classification of clinical events and should not contribute to the decision as to whether to refer a patient for monitoring.

Purpose: We investigated the association of severity of hypometabolism detected by positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) and persistence of interictal EEG focal slowing in patients with refractory temporal lobe epilepsy., Methods: Eighty temporal lobes of 40 consecutive patients with intractable temporal lobe epilepsy (mean age, 43.5 years) were studied. All patients underwent video-EEG monitoring, magnetic resonance imaging (MRI), and FDG-PET. Patients with either normal MRI or with unilateral mesial temporal sclerosis, but no other structural abnormality, were included. Interictal EEG delta slowing was graded as none, infrequent (one episode or less/hour), intermediate (more than one episode/hour), or continuous. PET hypometabolism was graded as none, mild, moderate, or severe., Results: The severity of temporal lobe hypometabolism with PET was significantly correlated with the amount of delta activity in the interictal EEG, independent of MRI findings (Spearman r = 0.46; p < 0.0005)., Conclusions: This observation suggests related underlying pathophysiologic mechanisms for metabolic and electrical dysfunction in temporal lobe epilepsy.

Phosphate mining operations in southeastern Idaho have exposed selenium (Se) that was originally sequestered in the subsurface. Sheep grazing in these areas have died as a result of high Se concentrations in forage and water. This study was designed to monitor the health status of sheep grazing in a natural environment with known elevated levels of Se. A total of 72 Columbia x Suffolk sheep were divided into 3 treatment groups that included control (Con), low selenium (LoSe) and high selenium (HiSe). The baseline phase of the study was conducted in an area with normal background Se levels in forage and water, and was grazed for 3 w by all sheep groups. The sheep then were moved onto reclaimed mine areas to begin the 4-w exposure phase. This was followed by a 2-w depuration phase where sheep again received normal Se levels in forage and water. The Con group was held on areas with normal Se levels of forage (< 0.32 ppm Se dw) and water (< 1.70 ppb Se). The LoSe group was held in an area of elevated forage Se (< 13.0 ppm Se dw) and normal Se levels in their water (< 1.70 ppb Se) during the exposure phase. The HiSe group was held on mining areas with elevated Se forage (< 49.0 ppm Se dw) and drinking water (340 to 415 ppb Se). Whole blood and serum levels in the HiSe group peaked at 1.32 and 0.99 ppm mean Se, respectively. The LoSe group had mean whole blood and serum Se levels of 0.75 ppm on day 42 and 0.32 ppm on day 35 respectively. The Con group maintained low Se levels in both whole blood and serum that ranged from 0.05 to 0.14 ppm and 0.06 to 0.13 ppm respectively. The Se exposure in the HiSe group was estimated 0.26 mg Se/kg body weight/d. One sheep in the HiSe group died and was diagnosed with Se toxicosis based on clinical signs, histopathology and tissue Se levels. Se in liver (3.90 ppm), kidney (1.90 ppm) and skeletal muscle (0.70 ppm) were indicative of high to toxic Se exposure. Two other sheep necropsied after the exposure phase also had Se concentrations in liver, kidney and skeletal muscle representative of high or toxic Se exposure (5.50, 3.50 and 1.10 ppm Se), but these sheep had no gross or histopathological signs of illness. More research is needed on the toxicology of Se in sheep grazing natural settings.

Purpose: High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES., Methods: After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant., Results: When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain., Conclusions: During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.