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Objective: Seizure clusters are often encountered in people with poorly controlled epilepsy. Detection of seizure clusters is currently based on simple clinical rules, such as two seizures separated by four or fewer hours or multiple seizures in 24 h. Current definitions fail to distinguish between statistically significant clusters and those that may result from natural variation in the person's seizures. Ability to systematically define when a seizure cluster is significant for the individual carries major implications for treatment. However, there is no uniform consensus on how to define seizure clusters. This study proposes a principled statistical approach to defining seizure clusters that addresses these issues., Methods: A total of 533,968 clinical seizures from 1,748 people with epilepsy in the Seizure Tracker™ seizure diary database were used for algorithm development. We propose an algorithm for automated individualized seizure cluster identification combining cumulative sum change-point analysis with bootstrapping and aberration detection, which provides a new approach to personalized seizure cluster identification at user-specified levels of clinical significance. We develop a standalone user interface to make the proposed algorithm accessible for real-time seizure cluster identification (ClusterCalc™). Clinical impact of systematizing cluster identification is demonstrated by comparing empirically-defined clusters to those identified by routine seizure cluster definitions. We also demonstrate use of the Hurst exponent as a standardized measure of seizure clustering for comparison of seizure clustering burden within or across patients., Results: Seizure clustering was present in 26.7 % (95 % CI, 24.5-28.7 %) of people with epilepsy. Empirical tables were provided for standardizing inter- and intra-patient comparisons of seizure cluster tendency. Using the proposed algorithm, we found that 37.7-59.4 % of seizures identified as clusters based on routine definitions had high probability of occurring by chance. Several clusters identified by the algorithm were missed by conventional definitions. The utility of the ClusterCalc algorithm for individualized seizure cluster detection is demonstrated., Significance: This study proposes a principled statistical approach to individualized seizure cluster identification and demonstrates potential for real-time clinical usage through ClusterCalc. Using this approach accounts for individual variations in baseline seizure frequency and evaluates statistical significance. This new definition has the potential to improve individualized epilepsy treatment by systematizing identification of unrecognized seizure clusters and preventing unnecessary intervention for random events previously considered clusters., Competing Interests: Declaration of Competing Interest SC is the founder of EpilepsyAI, LLC. RM is the cofounder and owner of Seizure Tracker, LLC, cofounder of EpilepsyAI, LLC, and has received personal fees from Cyberonics, Courtagen, Engage Therapeutics, Brain Sentinel, Neurelis, UCB, and grants from the Tuberous Sclerosis Alliance. DG is on the medical advisory board of Magic Leap, and has received grant support from BIDMC and NIH T32NS048005. SH is on the Editorial Board of Epilepsy and Behavior. A patent application has been filed based on these results. The remaining authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: We conducted clinical testing of an automated Bayesian machine learning algorithm (Epilepsy Seizure Assessment Tool [EpiSAT]) for outpatient seizure risk assessment using seizure counting data, and validated performance against specialized epilepsy clinician experts., Methods: We conducted a prospective longitudinal study of EpiSAT performance against 24 specialized clinician experts at three tertiary referral epilepsy centers in the United States. Accuracy, interrater reliability, and intra-rater reliability of EpiSAT for correctly identifying changes in seizure risk (improvements, worsening, or no change) were evaluated using 120 seizures from four synthetic seizure diaries (seizure risk known) and 120 seizures from four real seizure diaries (seizure risk unknown). The proportion of observed agreement between EpiSAT and clinicians was evaluated to assess compatibility of EpiSAT with clinical decision patterns by epilepsy experts., Results: EpiSAT exhibited substantial observed agreement (75.4%) with clinicians for assessing seizure risk. The mean accuracy of epilepsy providers for correctly assessing seizure risk was 74.7%. EpiSAT accurately identified seizure risk in 87.5% of seizure diary entries, corresponding to a significant improvement of 17.4% (P = .002). Clinicians exhibited low-to-moderate interrater reliability for seizure risk assessment (Krippendorff's α = 0.46) with good intrarater reliability across a 4- to 12-week evaluation period (Scott's π = 0.89)., Significance: These results validate the ability of EpiSAT to yield objective clinical recommendations on seizure risk which follow decision patterns similar to those from specialized epilepsy providers, but with improved accuracy and reproducibility. This algorithm may serve as a useful clinical decision support system for quantitative analysis of clinical seizure frequency in clinical epilepsy practice., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: Due to variability in the patterns of propagation of interictal epileptiform discharges (IEDs), qualitative definition of the irritative zone has been challenging. Here, we introduce a quantitative approach toward exploration of the dynamics of IED propagation within the irritative zone., Methods: We examined intracranial EEG (iEEG) in nine participants undergoing invasive monitoring for seizure localization. We used an automated IED detector and a community detection algorithm to identify populations of electrodes exhibiting IED activity that co-occur in time, and to group these electrodes into communities., Results: Within our algorithmically-identified communities, IED activity in the seizure onset zone (SOZ) tended to lead IED activity in other functionally coupled brain regions. The tendency of pathological activity to arise in the SOZ, and to spread to non-SOZ tissues, was greater in the asleep state., Conclusions: IED activity, and, by extension, the variability observed between the asleep and awake states, is propagated from a core seizure focus to nearby less pathological brain regions., Significance: Using an unsupervised, computational approach, we show that the spread of IED activity through the epilepsy network varies with physiologic state., (Published by Elsevier B.V.)

Background: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa., Methods: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray's test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death., Results: 95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29-532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1-333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1-4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures., Conclusions: New-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.

Using approximations based on presumed U.S. time zones, we characterized day and nighttime seizure patterns in a patient-reported database, Seizure Tracker. A total of 632 995 seizures (9698 patients) were classified into 4 categories: isolated seizure event (ISE), cluster without status epilepticus (CWOS), cluster including status epilepticus (CIS), and status epilepticus (SE). We used a multinomial mixed-effects logistic regression model to calculate odds ratios (ORs) to determine night/day ratios for the difference between seizure patterns: ISE versus SE, ISE versus CWOS, ISE versus CIS, and CWOS versus CIS. Ranges of OR values were reported across cluster definitions. In adults, ISE was more likely at night compared to CWOS (OR = 1.49, 95% adjusted confidence interval [CI] = 1.36-1.63) and to CIS (OR = 1.61, 95% adjusted CI = 1.34-1.88). The ORs for ISE versus SE and CWOS versus SE were not significantly different regardless of cluster definition. In children, ISE was less likely at night compared to SE (OR = 0.85, 95% adjusted CI = 0.79-0.91). ISE was more likely at night compared to CWOS (OR = 1.35, 95% adjusted CI = 1.26-1.44) and CIS (OR = 1.65, 95% adjusted CI = 1.44-1.86). CWOS was more likely during the night compared to CIS (OR = 1.22, 95% adjusted CI = 1.05-1.39). With the exception of SE in children, our data suggest that more severe patterns favor daytime. This suggests distinct day/night preferences for different seizure patterns in children and adults., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: Seizure frequency variability is associated with placebo responses in randomized controlled trials (RCT). Increased variability can result in drug misclassification and, hence, decreased statistical power. We investigated a new method that directly incorporated variability into RCT analysis, Z V ., Methods: Two models were assessed: the traditional 50%-responder rate (RR50), and the variability-corrected score, Z V . Each predicted seizure frequency upper and lower limits using prior seizures. Accuracy was defined as percentage of time-intervals when the observed seizure frequencies were within the predicted limits. First, we tested the Z V method on three datasets (SeizureTracker: n=3016, Human Epilepsy Project: n=107, and NeuroVista: n=15). An additional independent SeizureTracker validation dataset was used to generate a set of 200 simulated trials each for 5 different sample sizes (total N=100 to 500 by 100), assuming 20% dropout and 30% drug efficacy. "Power" was determined as the percentage of trials successfully distinguishing placebo from drug (p<0.05)., Results: Prediction accuracy across datasets was, Z V : 91-100%, RR50: 42-80%. Simulated RCT Z V analysis achieved >90% power at N=100 per arm while RR50 required N=200 per arm., Significance: Z V may increase the statistical power of an RCT relative to the traditional RR50., (Published by Elsevier B.V.)

Objective: To identify the etiology of new-onset seizure in HIV-infected Zambian adults and identify risk factors for seizure recurrence., Methods: A prospective cohort study enrolling HIV-infected adults with new-onset seizure within 2 weeks of index seizure obtained clinical, laboratory, and neuroimaging data to determine seizure etiology. Participants were followed to identify risk factors for seizure recurrence. Risk factors for mortality were examined as mortality rates were unexpectedly high., Results: Eighty-one patients with CSF for analysis were enrolled and followed for a median of 306 days (interquartile range 61-636). Most (91%) were at WHO stage III/IV and 66 (81%) had a pre-seizure Karnofsky score ≥50. Prolonged or multiple seizures occurred in 46 (57%), including 12 (15%) with status epilepticus. Seizure etiologies included CNS opportunistic infections (OI) in 21 (26%), hyponatremia in 23 (28%), and other infections in 8 (10%). OIs included Cryptococcus (17%), JC virus (7%) and 5% each for tuberculosis, cytomegalovirus, and varicella-zoster virus. No etiology could be identified in 16 (20%). Thirty (37%) patients died during follow-up and 20 (25%) had recurrent seizures with survival being the only identifiable risk factor., Conclusions: HIV-infected adults with new-onset seizure in Zambia often have advanced HIV disease with OI being the most frequent seizure etiology. Seizure recurrence is common but no risk factors for recurrence other than survival were identified. These findings suggest an urgent need for immune reconstitution in this population. Initiating treatment for seizure prophylaxis where only enzyme-inducing antiepileptic medications are available could threaten antiretroviral efficacy., (© 2016 American Academy of Neurology.)

Objectives: The aim of the study was to describe patient characteristics and outcomes among HIV-positive adults presenting to a Zambian tertiary care hospital with new-onset seizures., Methods: From July 2011 to June 2013, adults with seizures and a known or probable diagnosis of HIV infection were screened for a cohort study. Demographic and clinical data were obtained, including information on engagement in HIV services and in-patient mortality. Analyses were conducted to identify characteristics associated with poor engagement in care and death., Results: A total of 320 of 351 screened adults were HIV-positive, with 268 of 320 experiencing new-onset seizures. Of these, 114 of 268 (42.5%) were female, and their mean age was 36.8 years. Seventy-nine of the 268 patients (29.5%) were diagnosed with HIV infection during the index illness. Among those who were aware of their HIV-positive status, 59 of 156 (37.8%) had disengaged from care. Significant functional impairment (Karnofsky score < 50) was evident in 44.0% of patients. Cerebrospinal fluid was not obtained in 108 of 268 (40.3%). In-patient mortality outcomes were available for 214 patients, and 47 of these 214 (22.0%) died during hospitalization. Patients with significant functional impairment were more likely to undergo lumbar puncture (P = 0.046). Women and the functionally impaired were more likely to die (P = 0.04 and < 0.001, respectively)., Conclusions: Despite the availability of care, less than half of HIV-infected people with new-onset seizures were actively engaged in care and in-patient mortality rates were high. In the absence of clinical contraindication, lumbar puncture should be performed to diagnose treatable conditions and reduce morbidity and mortality. Continued efforts are needed to expand community-based testing and improve HIV care retention rates. Qualitative studies are needed to elucidate factors contributing to lumbar puncture usage in this population., (© 2015 British HIV Association.)

Objective: To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure., Methods: Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome., Results: Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103-560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051)., Conclusions: EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis., (© 2015 American Academy of Neurology.)

A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging., (© The American Society of Tropical Medicine and Hygiene.)

Dysembryoplastic neuroepithelial tumours (DNET) are a common cause of tumour-associated epilepsy, and are usually located in the temporal lobes. We present a case of multifocal DNETs in both infra- and supra-tentorial locations, in a 23-year-old man with a coincident Type I Chiari malformation, presenting with medically refractory focal seizures. The extensive anatomical distribution of the lesions suggests a genetic component in their tumourigenesis.

Purpose: To determine the effect of seizure focus location within the left hemisphere on the expression of regional language dominance., Methods: In this cross-sectional study we investigated 90 patients (mean age 23.3 ± 12.9 years) with left hemisphere focal epilepsy (mean age onset 11.7 ± 8.3 years). Eighteen patients had a frontal lobe focus and 72 had a temporal lobe focus (43 mesial; 29 neocortical). Subjects performed an auditory word definition language paradigm using 3 Tesla blood oxygen level dependent (BOLD) EPI functional magnetic resonance imaging (fMRI). Data were analyzed in SPM2. Regional laterality indices (LIs) for inferior frontal gyrus (IFG), and Wernicke's area (WA), were calculated using a bootstrap method. Categorical language dominance and mean LI were analyzed., Key Findings: Mean WA LI was lower for subjects with a mesial temporal focus compared with a frontal focus (p = 0.04). There was a greater proportion of atypical language in WA for subjects with a mesial temporal focus compared with a frontal focus (χ(2) = 4.37, p = 0.04). WA LI did not differ for subjects with a neocortical focus compared with a mesial focus or a frontal focus. Mean IFG LI and proportion of atypical language in IFG were similar across seizure focus groups. Age and age of onset were not correlated with mean laterality in WA or IFG. Epilepsy duration tended to be negatively correlated with WA LI (r = -0.18, p = 0.10), but not IFG LI., Significance: Temporal lobe foci have wide-ranging effects on the distributed language system. In contrast, the effects of a frontal lobe focus appear restricted to anterior rather than posterior language processing areas., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Background: Previous studies have shown that status epilepticus can lead to neuronal injury. However, the effect of a small number of isolated seizures is uncertain., Methods: We used structural MRI and neuropathology to study the effects of isolated seizures induced by kainic acid (KA), (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazole-4-yl)propanoic acid (ATPA), and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate in rats. A group of animals received normal saline. After seizure induction, animals were followed for 12 weeks., Results: ATPA and KA led to small but significant increases in ADC. There were no changes in T2 signal intensity or hippocampal volume. Blinded pathological examination showed no differences between animals receiving saline or glutamatergic agents., Conclusion: Our study suggests that isolated seizures cause minimal neuronal injury in rats., (Published 2011. This article is a US Government work and is in the public domain in the USA.)

Postictal behaviors and symptoms often require special assessment and treatment. We review risk factors for postictal delirium and psychosis and management of agitated and confused behaviors in patients after seizures. Medical and emergency staff require careful training to manage behaviors associated with postictal delirium and psychosis in order to protect patients while their confusion resolves. Treatment of postictal states requires recognition of underlying neurological and systemic disorders associated with seizures and delirium such as metabolic disorders and nonconvulsive seizures. There is incomplete information about the causes and optimal treatments for seizure-related psychosis, however, postictal behaviors can usually be managed safely., (Copyright © 2010 Elsevier Inc. All rights reserved.)

There is relatively little information on the underlying parameters that affect clinical features of the postictal period. Age-related physiological changes, including alterations in cerebral blood flow and metabolism, neurotransmitter function, and responses of the brain to seizure activity may affect postictal clinical phenomena. Some conclusions can be drawn. Elderly adults and children, particularly in the presence of diffuse cerebral dysfunction, may have more prolonged postictal confusion. Postictal dysphasia strongly suggests a dominant hemisphere focus, more often temporal, and Todd's paralysis is always contralateral to the epileptogenic zone. Much additional information could be derived from the vast amount of video/EEG monitoring data available., (Published by Elsevier Inc.)

Objectives: To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering., Patients and Methods: We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared., Results: All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05)., Conclusions: Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted.

Objective: To reassess the value of neuroimaging of the emergency patient presenting with seizure as a screening procedure for providing information that will change acute management, and to reassess clinical and historical features associated with an abnormal neuroimaging study in these patients., Methods: A broad-based panel with topic expertise evaluated the available evidence based on a structured literature review using a Medline search from 1966 until November 2004., Results: The 15 articles meeting criteria were Class II or III evidence since interpretation was not masked to the patient's clinical presentation; most were series including 22 to 875 patients. There is evidence that for adults with first seizure, cranial CT will change acute management in 9 to 17% of patients. CT in the emergency department for children presenting with first seizure will change acute management in approximately 3 to 8%. There is no clear difference between rates of abnormal emergent CT for patients with chronic seizures vs first. Children <6 months presenting with seizures have clinically relevant abnormalities on CT scans 50% of the time. Persons with AIDS and first seizure have high rates of abnormalities, and CNS toxoplasmosis is frequently found. Abnormal neurologic examination, predisposing history, or focal seizure onset are probably predictive of an abnormal CT study in this context., Conclusions: Immediate noncontrast CT is possibly useful for emergency patients presenting with seizure to guide appropriate acute management especially where there is an abnormal neurologic examination, predisposing history, or focal seizure onset.

Purpose: Hypothalamic hamartomas (HHs) have been associated with uncontrolled seizures, and aggressive therapy including surgery is often recommended. However, some patients, particularly those with other findings associated with Pallister-Hall syndrome (PHS), have a more benign course., Methods: Thirty-seven of 40 PHS patients and 16 of 16 patients with isolated HH had a lesion confirmed on magnetic resonance imaging (MRI). Records for all patients were reviewed for the following information: presence of seizures, age at seizure onset, seizure type, seizure frequency, number of antiepileptic medications (AEDs) at the time of evaluation, past AEDs, MRI characteristics of the HH, presence of endocrine dysfunction, and presence of developmental and behavioral problems., Results: All isolated HH patients had a history of seizures, compared with 13 of 40 PHS patients (all PHS patients with seizures had hamartomas). In isolated HH, seizures started earlier in life, occurred more frequently, and were harder to control than those in patients with PHS. Isolated HH patients were more likely to have behavioral and developmental problems than were PHS patients. The T2 signal of the hamartoma was isointense to gray matter in the majority of PHS patients, but showed a significant increase in all but one patient with isolated HH., Conclusions: Patients with isolated HH have a distinct clinical phenotype, showing more severe seizures and neurologic dysfunction, HH showing increased T2 signal, and are more likely to have precocious puberty. In contrast, PHS patients usually have well-controlled seizures and other endocrine disturbances than precocious puberty. Patients with HH with or without seizures should be evaluated carefully for other clinical manifestations of PHS, particularly before surgery is considered.

Objective: To characterize the cognitive deficits in children with gelastic seizures and hypothalamic hamartoma and investigate the relationship of seizure severity to cognitive abilities., Methods: Eight children with gelastic seizures and hypothalamic hamartoma completed a neuropsychological battery of standardized and age-normed tests, including the Woodcock-Johnson Psycho-Educational Battery-Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III, and initial-letter word fluency measure., Results: All children displayed cognitive deficits, ranging from mild to severe. Gelastic/complex partial seizure severity was correlated with broad cognitive ability standard scores (r = -0.79; r2 = 0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures was also correlated with broad cognitive ability standard scores (r = -0.72; r2 = 0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score differences were found, with relative weaknesses in long-term retrieval (mean = 64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual processing differed from performance in long-term retrieval (p = 0.009) and processing speed (p = 0.029)., Conclusion: These findings are consistent with cognitive functions and affective/emotional states associated with conduction pathways of the hypothalamus involving cortical association areas and amygdala and hippocampal formation. These abnormalities can account for the prominent deficit found in integrating information in the processing of memories.

A 28-year-old woman with epilepsy developed the new onset of paroxysmal tongue tingling during subdural electrode monitoring. Her symptoms coincided with electrographic seizure activity arising from an area of the perisylvian region that had not previously been involved in her habitual seizures. At electrode removal, a focal 2 x 2 cm hematoma was detected and evacuated from beneath these electrode contacts. Unexpected episodic events may represent nonhabitual seizure activity related to the surgical procedure.

Objective: To examine the time course of alterations in glucose metabolism in relation to the interval from the last seizure, focus laterality, seizure frequency, and seizure type., Design: Metabolic study with the use of positron emission tomography with fludeoxyglucose F 18. Blinded scan evaluation with use of a standard template. Multivariate regression analysis of positron emission tomographic data., Setting: National Institutes of Health Clinical Center, Bethesda, Md., Patients: Thirty-two adults with intractable partial epilepsy and lateralized seizure onset documented by video-electroencephalographic monitoring., Main Outcome Measure: Normalized metabolic rate for glucose ipsilateral and contralateral to the epileptic focus., Results: The most dramatic changes occurred in inferior temporal regions; the midtemporal region was affected as well. Effects lasting 48 hours were found after both simple and complex partial seizures. The time course was different for the two types of seizures. The inferior temporal metabolic rate ipsilateral to the focus increased compared with the interictal rate during the 24-hour period following simple partial seizures; a nadir occurred in the second 24 hours. The rate then rose to an intermediate level after 48 hours. The relative to an intermediate level after 48 hours. The relative regional increase in ipsilateral metabolism following complex partial seizures persisted for 48 hours before falling., Conclusion: The brain may take longer than 24 hours after a partial seizure to return to its baseline state.

Antiepileptic drug (AED) levels are obtained frequently in clinical practice, but their complex relation to seizures or drug toxicity often makes interpretation of the results difficult. Research studies have not always taken into account clinical, as well as pharmacokinetic and pharmacodynamic, factors which may influence the drug level-effect relationship. AED levels should be drawn at an appropriate time in relation to drug ingestion and clinical symptoms. Systematic investigations in selected patients, during which several levels are obtained, may be more rewarding than routine measurements in a large clinic population.

We studied patients with partial and primary generalized seizures using fluorine-18-labeled 2-fluorodeoxyglucose and positron emission tomography. Interictal studies of patients with partial seizures showed regions of focal or lateralized hypometabolism in 15 of 17 patients with unilateral electroencephalographic foci. Several patients had more than one hypometabolic region. In 1 patient PET hypometabolism was contralateral to the electroencephalographic epileptic focus. Six of 10 patients without definite electroencephalographic foci also showed unilateral PET hypometabolic regions. PET during complex partial seizures in 3 patients showed hypermetabolism at the site of the hypometabolic focus. A postictal scan in 1 patient showed extension of interictal temporal hypometabolism to the frontal lobe as well. Interictal scans in 8 patients with primary generalized seizures did not reveal any hypometabolic regions. One patient scanned during an attack of absence status epilepticus showed a slight decrease in metabolic rate compared to the interictal scan. Temporal lobectomy has been performed in 6 patients with focal PET hypometabolism. PET may obviate the need for depth electrode study in some patients with intractable partial seizures.

Seventy-four patients with intractable seizures were followed up 6 to 57 months (mean 25 months) after intensive monitoring. At discharge from the hospital, 59% of the patients had at least a 50% reduction in seizure frequency and 63% had decreased antiepileptic drug toxicity. The findings at follow-up compared with those at admission showed reduced seizure frequency in 55% of the patients, diminished medication toxicity in 54%, and improved social adjustment in 38%. A change in the seizure diagnosis was the best predictor of a favorable outcome. Patients with impaired mental status were not less likely to improve. The relationship between seizure type and outcome was not significant, although patients with complex partial seizures tended to be less likely to improve. Intensive monitoring can lead to significant long-lasting improvement of patients with severe epilepsy.

We report the cases of 3 patients with medically intractable seizures in whom withdrawal of treatment with a long-acting benzodiazepine (clorazepate dipotassium, 2 patients; clonazepam, 1 patient) was followed by delirium with catatoniclike features. While an increase in seizure frequency occurred during withdrawal and prior to the onset of behavioral changes, electroencephalograms did not show epileptiform activity during the delirium. We compared these 3 patients with 10 others with intractable seizures in whom antiepileptic therapy was withdrawn without subsequent behavior changes. High-dose benzodiazepine therapy and a history of viral encephalitis may be risk factors for withdrawal delirium.

We studied 21 patients with complex partial seizures during phenobarbital (PB) or primidone withdrawal. Blood levels were measured daily, and seizure frequency was monitored by nursing staff and EEG-video telemetry. Patients were monitored for one week of baseline and for five weeks after PB tapering was initiated (withdrawal). Most were observed for at least one week after levels were undetectable. When ranked seizure counts were averaged, there was a tendency for seizure rates to be highest as PB levels passed through the range 15 to 20 mg/l, compared with rates at higher or lower PB levels. There was little or no relation between the rate of PB withdrawal, other drug therapy, or initial PB level and the ratio of highest seizure frequency to mean seizure frequency. Patients withdrawing from PB may be most likely to experience an increase in seizure frequency when their PB blood level falls below 20 mg/l.

We used serial positron emission tomography scans with [18F]2-deoxyglucose to study the effect of phenytoin on human cerebral glucose metabolism in 10 patients with seizure disorders. Local CMRglu for each patient was measured in 10 regions of interest. EEGs were performed during each procedure to match scans for state of consciousness and exclude data from scans with ictal activity. Serial scans without a drug change were performed in six control patients. Metabolic rates were significantly lower in two cortical regions while patients were taking phenytoin. No significant changes on repeat scan were seen in the control population. Measured across all regions of interest, metabolic rates were 13% higher when patients were off phenytoin (p less than 0.02).

We analyzed local cerebral metabolic rates of glucose (LCMRglu) in 20 regions from 22 patients with complex partial seizures, who were taking neither phenytoin nor phenobarbital and who had normal CTs. Results were compared with data from 19 normal controls. Ten patients had left temporal, eight right temporal, and four bitemporal or generalized EEG discharges. There were no significant differences between patient and control values in any of 20 regions of interest. LCMRglu was depressed at the site of the epileptic focus: L/R ratio was 0.85 +/- 0.12 (p less than 0.003 compared with control), 0.92 +/- 0.08 (p less than 0.05), and 0.84 +/- 0.1 (p less than 0.001), respectively, in mesial, superior, and inferior temporal regions for patients with left temporal foci; 1.7 +/- 0.96 (p less than 0.04), 1.1 +/- 0.1 (NS), and 1.15 +/- 0.04 (p less than 0.001) for patients with right temporal foci. Patients with left temporal EEG foci had significantly lower values than patients with right temporal foci in left superior frontal and thalamic as well as left temporal regions, while patients with right-sided EEG foci had depressed LCMRglu (compared with patients with left temporal EEG foci) restricted to right mesial temporal lobe. The patients with left temporal foci tended to have longer seizure histories (22.7 +/- 5.4 versus 11 +/- 5.6 years; p less than 0.001). There was an inverse correlation between length of seizure history and mean LCMRglu (r = 0.38; 0.1 greater than p greater than 0.05). Our study suggests that LCMRglu is not depressed in regions beyond the epileptic focus when patients are not taking drugs known to decrease cerebral glucose metabolism.

We used subdural electrodes to study the EEG features of simple partial seizures in 7 patients. We detected epileptiform discharges in 61 of 68 subdurally recorded simple partial seizures compared with 6 of 55 simple partial seizures recorded with scalp electrodes (p less than 0.0001). The onset of 36 nonmotor simple partial seizures was detected only by the medial and basal temporal subdural electrodes, and the onset of 25 simple partial seizures with motor manifestations was recorded by subdural electrodes only from the lateral cortex of the posterior frontal lobe. There was a close correspondence between the area first involved in the epileptiform discharge during simple partial seizures and the area first involved during complex partial and secondary generalized tonic-clonic seizures. Subdural electrodes may be effective in localizing the onset and spread of simple partial seizures, including those that arise from the medial temporal lobe.