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Background and Objectives: Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months., Methods: This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records., Results: A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10)., Discussion: The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.

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.)

Cognitive impairment and personality disorders are severe comorbidities commonly observed in patients with epilepsy, and together they decrease the quality of patients' life. This study aimed to evaluate cognitive function and personality traits in patients with epilepsy with the Wechsler Adult Intelligence Scale-Chinese revised and Eysenck Personality Questionnaire and investigate the underlying influencing factors. Compared with the control group, our results showed that patients with epilepsy were presented with significant cognitive impairment and particular personality traits. Epileptic seizure-related factors including earlier age of onset, longer duration of epileptic history, and higher seizure frequency were significantly associated with the observed defects in cognition and personality traits. In addition, the temporal lobe was more likely to affect cognition and personality, and the left hemisphere was closely related to verbal intelligence quotient, which needs to be the focus of future research. These results will be instrumental for guiding the treatment of epilepsy.

Objective: In this study, we aimed to uncover distinct antecedents of autobiographic memory dysfunction in patients with epilepsy with early (childhood/adolescence) vs late (adulthood) disease onset., Methods: One hundred sixty-six adults participated: 92 patients with focal epilepsy, whose cognitive and psychiatric functioning were compared to that of 74 healthy controls. Predictors of autobiographic memory deficit were contrasted between patients with early-onset (n = 47) vs late-onset (n = 45) epilepsy., Results: Overall, people with epilepsy performed significantly worse on measures of both semantic and episodic autobiographic memory and showed markedly high rates of depressive symptoms and disorders (p < 0.001). Reduced autobiographic memory in patients with early-onset epilepsy was associated with young age at onset, more frequent seizures, and reduced working memory. In contrast, the difficulty that patients with late-onset epilepsy had in recalling autobiographic information was linked to depression and the presence of an MRI-identified lesion., Conclusions: This study reveals that memory deficits in people with focal epilepsy have differing antecedents depending on the timing of the disease onset. While neurobiological factors strongly underpin reduced autobiographic function in patients with early-onset epilepsy, psychological maladjustment gives rise to the impairments seen in patients with late-onset epilepsy. More broadly, these findings support the practice of subtyping patients according to distinct clinical characteristics to find individualized predictors of cognitive dysfunction., (© 2016 American Academy of Neurology.)

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness., Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients)., Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment., Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

Objectives: 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., Methods: A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation., Results: Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function., Conclusions: Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures., Classification of Evidence: This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Objective: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed., Methods: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis., Results: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering., Conclusions: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.

Objectives: Previous research has demonstrated that alpha2 agonists improve working memory performances in healthy individuals and in primates with prefrontal lesions. We conducted this study to determine whether the alpha2 agonist, guanfacine, could improve working memory performances in patients with frontal lobe epilepsy (FLE) and/or in those with focal epilepsy outside the frontal lobes (ie, temporal lobe epilepsy [TLE])., Methods: Fourteen patients with FLE, 13 patients with TLE, and 10 healthy controls completed immediate and delayed match-to-sample tasks before and after ingestion of 2 to 3 mg of guanfacine., Results: All 3 groups showed an increase in accuracy on the delayed match-to-sample task, but not the immediate match-to-sample task, following administration of guanfacine. Inspection of the group means revealed somewhat greater benefits for the control and FLE groups relative to the TLE group. Increased accuracy was not associated with slower performances in any group, suggesting that the cognitive benefits of guanfacine did not occur at the expense of increased sedation., Conclusions: These data suggest that guanfacine improves working memory in patients with FLE and may be a viable treatment for attenuating such deficits in this patient population.

The authors describe a 16-year-old patient with recurrent episodes of epileptic linear self-motion perception and occasional body tilts. Intracranial seizure monitoring located the seizure onset, caused by a circumscribed ependymoma, in the right paramedian precuneus. Electrical cortical stimulation of this area could reproduce the same vestibular sensations, which ceased after lesionectomy. The findings implicate the paramedian area of the precuneus in the processing of static and dynamic vestibular, probably otolithic, information.

Background: fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis., Objective: To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation., Methods: Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L-R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT)., Results: The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis., Conclusions: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.

A total of 340 patients age 50 years and older were compared with 30 patients younger than 50 years, all of whom had anterior temporal lobectomy for refractory epilepsy. Seizure outcome, neuropsychological test scores, and change in driving status were analyzed. Age and duration of epilepsy were related independently to outcome, but laterality of interictal sharp waves (an early epilepsy risk factor) and presence of tumor were not. Sixteen patients (52%) in the older group and 257 patients (75.6%) in the younger group (p < 0.008) were seizure free. Postoperative neuropsychological outcome and driving status were similar in older and younger patients.

Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation., Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures., Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline., Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred., Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta 1 and beta 2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

Background: Assessment of language organization is crucial in patients considered for epilepsy surgery. In children, the current techniques, intra-carotid amobarbital test (IAT) for language dominance, and cortical electrostimulation mapping (ESM), are invasive and risky. Functional magnetic resonance imaging (fMRI) is an alternative method for noninvasive functional mapping, through the detection of the hemodynamic changes associated with neuronal activation. We used fMRI, to assess language dominance in children with partial epilepsy., Methods: Eleven right handed children and adolescents performed a word generation task during fMRI acquisition focused on the frontal lobes. Areas where the signal time course correlated with the test paradigm (r = 0.7) were considered activated. Extent and magnitude of signal changes were used to calculate asymmetry indices. Seven patients had IAT, ESM, or surgery outcome available for comparison., Results: fMRI language dominance always agreed with IAT (6 cases) and ESM (1 case), showing left dominance in six and bilateral language in one. fMRI demonstrated left dominance in three additional children, and right dominance in one with early onset of left temporal epilepsy. Four children whose initial studies were equivocal due to noncompliance or motion artifacts were restudied successfully., Conclusions: fMRI can be used to assess language lateralization noninvasively in children. It has the potential to replace current functional mapping techniques in patients, and to provide important data on brain development.

In a prospective study lasting 6 months, we recorded on video 108 seizures with aura of 23 patients in an attempt to evaluate the mechanisms involved in the encoding of memories. In 88 of those seizures, we also recorded an EEG. The percentage of auras remembered decreased significantly with increasing severity of the seizures. The recollection of auras was also significantly dependent on the ictal EEG changes during the aura. Ninety-seven percent of the auras without EEG changes, 94% of the auras with unilateral EEG changes, and 73% of the auras with bilateral EEG changes during the aura were remembered. The spread of the ictal EEG pattern during the aura also showed a significant correlation with the severity of the ensuing seizure. Three patients with bitemporal epilepsy made up a considerable proportion of those who never remembered their aura before secondary generalized tonic-clonic seizures (2 of 3) and of those who had a transient postictal amnesia of their aura (2 of 3). The only patient who failed to remember a previously documented isolated aura also suffered from bitemporal epilepsy. During the second part of the study, we questioned whether information provided during the history could be helpful in defining the type of epilepsy syndrome or localizing the EEG seizure pattern of the 80 patients who had been admitted for presurgical epilepsy diagnosis. Localized (regional, unilateral, and independent left and right lateral) EEG seizure patterns occurred in 82% of the 51 patients with auras in their history as compared with 24% of the 17 patients who did not have auras in their history (p < 0.01).

We gave 58 patients with refractory partial seizures who were undergoing video-EEG telemetry a variety of memory tests shortly after the telemetry commenced, and we reassessed memory for this material 48 hours later. Thirty patients had one or more seizures during this period; 22 of these had complex partial seizures, secondary generalized seizures, or both. Eighteen patients did not have any seizures during the study period. Patients who had seizures forgot no more than patients who did not have seizures. There was no correlation between memory performance and the timing of seizures or the number of seizures. These findings indicate that isolated seizures do not generally cause patients to forget material they have recently learned.

Doubts concerning the localizing significance of auras in partial seizures have recently been expressed. Prompted by this, we studied this issue by re-examining two groups of patients; the first, studied retrospectively, consisted of patients in whom the site of origin of the seizures was known beyond a reasonable doubt; the second, studied prospectively, comprised patients in whom specific auras were correlated with the localization of interictal epileptiform EEG abnormalities and the final diagnostic impression. The data from the retrospective series were suitable for rigorous statistical analysis. The two groups yielded similar results: the frequency of auras in partial seizures and the localizing significance of those for which large enough numbers could be collected was high. We conclude that the type of aura, when elicited by careful history-taking, provides as useful localizing, but often not lateralizing, information as the EEG and modern high-technology procedures such as CT, MRI, and PET.

In the present investigation, the dichotic word listening performance of a sample of 25 dysphoric neuropsychiatric patients who endorsed multiple partial seizure-like symptoms was compared with that of matched samples of normal controls and patients with mood disorders who did not endorse multiple seizure-like symptoms. Eighty percent of the patients who endorsed multiple episodic phenomena failed the dichotic listening task, compared with 8% of normal controls and 28% of patients with typical mood disorders. After treatment with carbamazepine, a subsample of polysymptomatic patients manifested significantly fewer seizure-like symptoms. This clinical improvement was typically associated with markedly improved dichotic listening performance in most cases. The results are consistent with our previous hypothesis that "subclinical" electrophysiological dysfunction may severely disrupt the normal transmission and processing of auditory information. Because it is sensitive to this type of presumed cerebral dysfunction and relatively specific, impaired dichotic listening performance is likely to be a useful clinical marker for this complex neuropsychiatric syndrome.

Neuropsychological performance data from 106 children with epilepsy were evaluated to determine the effects of seizure type and age of onset. The performance of children with partial seizures (N = 49) was similar to that of children with generalized seizures (N = 57). Only one of 13 tests showed a significant difference between groups, with children with partial seizures performing better on that test. The effects of age of onset were also similar in the two seizure groups. Children whose seizures began before the age of 5 years performed significantly worse than children whose seizures began later on four measures (Verbal IQ, Performance IQ, Trails A, and Trails B) and performed more poorly, but not significantly so, on the other nine measures in the battery. A breakdown of the partial group into simple partial, complex partial, and secondarily generalized partial seizure groups found a significant difference between the groups on only one variable, but there were suggestions in the data that the performance of the partial secondarily generalized group was worse than the other two groups. These results indicate that variables associated with an early onset of seizures, regardless of type, place a child at risk for cognitive dysfunction.

The antiepileptic effect of clorazepate when given with phenytoin was compared, in a randomized double-blind crossover study, to the effect of the standard regimen of phenobarbital plus phenytoin in patients with partial seizures. Thirty of 42 subjects preferred the clorazepate-phenytoin regimen (p less than 0.01). The same number of subjects had fewer seizures while taking clorazepate as had fewer seizures while taking phenobarbital. However, subjects had significantly more toxicity, objective and subjective, on the phenobarbital-phenytoin regimen (p less than 0.01 in both cases). In some subjects, increased toxicity due to phenobarbital outweighed better seizure control, so that clorazepate was preferred. As an add-on antiepileptic drug, clorazepate is well tolerated, effective, and preferred by most patients to phenobarbital.

The electroencephalogram (EEG) in a case of multiple personality was described. Despite conflicting reports in the literature we found no changes in the EEG which could not be ascribed to the normal changes seen in transitions from various states of alertness. The problems of differentiating multiple personality as a psychiatric entity in itself from those cases arising as a result of chronic partial or partial-complex epilepsy are discussed. Further research with more sophisticated electrophysiological data acquisition and data reduction equipment is suggested.

We assessed the hypothesis that psychopathology is overrepresented in patients with temporal lobe epilepsy (TLE) who experience ictal fear. Eleven such patients were matched with two control groups: patients who had TLE without ictal fear and patients who had generalized epilepsy. On several MMPI scales, the TLE-ictal fear group scored significantly higher than the two control groups, which did not differ significantly from each other. Furthermore, the TLE-ictal fear group had more MMPI clinical scales that were pathologically elevated, had significantly more patients with histories of admission to psychiatric hospitals, and had more MMPI profiles that were psychotic than either of the control groups.

In order to evaluate the effect of lateralization of epileptogenic lesions on mood changes (depression-mania) and anxiety (state and trait), twenty patients with complex partial seizures and nineteen controls were assessed with depression scales (Beck, Columbia M-D) and the State and Trait Anxiety Inventory. Nine patients had left temporal foci, eight had right foci, as assessed by the side of seizure onset during closed-circuit television-EEG telemetry recording. Left patients scored significantly higher than both right and control groups on depression and trait anxiety. Our results are consistent with those of previous reports on patients with localized epileptogenic and nonepileptogenic lesions. Patients with left side involvement seem more prone to experience dysphoric changes and depressive symptoms than those with right involvement.

There is much evidence that emotional stess can trigger both neurogenic and hysterical seizures in susceptible patients. We reviewed out experience with 37 patients whose seizures appeared to be precipitated at times by emotional stress and had not been controlled by anticonvulsant medication alone. Approximately 70 per cent of patients demonstrated substantial improvement in seizure control after psychiatric treatment and maintained this improvement during follow-up. The findings of this study suggest that patient characteristics associated with better prognosis include normal intelligence, partial (as opposed to generalized) neurogenic seizures, a diagnosis of hysterical seizures, a less severely abnormal EEG, and being hypnotizable. After psychiatric treatment, 32 per cent of patients had their anticonvulsant medication reduced and another 16 per cent had it discontinued.