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An exploratory analysis from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray for acute treatment of seizure clusters assessed the use of a second dose up to 24 hours after the initial dose and effectiveness in potentially reducing the number of seizures.Seizures and doses were recorded in diaries.Of 175 patients enrolled, 163 received ≥1 dose of diazepam nasal spray and were included in the safety population; those patients received a total of 4390 doses for a total of 3853 seizure clusters. Less than half of these patients used a second dose a least once during the study (79 patients [48.5%]), with a total of 485 second doses for seizure clusters (12.6% of all seizure clusters). Among these 79 patients, 33 (41.8%) used only one second dose during the study (range: 1-82). The proportion of seizure clusters treated with a second dose over time was consistently low across 24 h: 0-4 h, 152 (3.9%); 4-6 h, 72 (1.9%); 6-8 h, 39 (1.0%); 8-12 h, 55 (1.4%); 12-16 h, 42 (1.1%); 16-20 h, 42 (1.1%); 20-24 h, 83 (2.2%). Rates of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs occurring within 1 day of a second dose were low (15.2% and 5.1%, respectively).Patients with epilepsy may experience seizure clusters lasting up to 24 hours, and little is known about the effectiveness of rescue therapies for that duration. The current labeling of the US Food and Drug Administration (FDA)-approved outpatient treatments for seizure clusters (rectal diazepam, intranasal midazolam, and diazepam nasal spray) allows for a second dose, if needed, for control. These findings support the safety profile of second doses, and the low use supports the effectiveness of diazepam nasal spray across 24 hours.

Objective Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement. Methods This phase 3, open‐label, repeat‐dose, safety study of diazepam nasal spray enrolled patients (6‐65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (5, very‐high frequency). Safety was evaluated based on treatment‐emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness. Results Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment‐related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate‐, high‐, and very‐high‐frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use. Significance Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of 5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.

Objective Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods A long‐term, phase 3, open‐label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no‐benzodiazepine group. Findings were similar in a sub‐analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. Significance This analysis of patients from a long‐term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub‐analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

OBJECTIVE: Classification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks. METHODS: We used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes. RESULTS: A total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types. SIGNIFICANCE: Quantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

The objective of this study was to describe serological association of musicogenic epilepsy and to evaluate clinical features and outcomes of seropositive cases. Through retrospective chart review, musicogenic epilepsy patients were identified. Among 16 musicogenic epilepsy patients, nine underwent autoantibody evaluations and all had high-titer glutamic acid decarboxylase 65-immunoglobulin G (GAD65-IgG; >20 nmol·L-1 , serum, normal ≤ .02 nmol·L-1 , eight women). Median GAD65-IgG serum titer was 294 nmol·L-1 (20.3-3005 nmol·L-1 ), and median cerebrospinal fluid titer (n = 4) was 14.7 nmol·L-1 . All patients had temporal lobe epilepsy, and bitemporal epileptiform abnormalities were common. Right temporal lobe seizures were most frequently captured when seizures were induced by music on electroencephalogram (3/4; 75%). Intravenous (IV) methylprednisolone and/or IV Ig (IVIG) was utilized in four patients, with one having greater than 50% reduction. Rituximab (n = 2) and mycophenolate (n = 1) were ineffective. Two patients underwent right temporal lobe resections but continued to have seizures. Vagus nerve stimulation was effective at reducing seizures in one patient by 50%, and an additional patient was seizure-free by avoiding provoking music. Right temporal lobe epilepsy was more common among patients with musicogenic epilepsy when compared to nonmusicogenic GAD65 epilepsies (n = 71, 89% vs. 47%, p = .03). GAD65-IgG should be tested in patients with musicogenic epilepsy, given implications for management and screening for comorbid autoimmune conditions.

Summary Two patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep-activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case one is a 59 year old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct eight hour long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case two is a 50 year old woman with known focal epilepsy also presented with memory complaints. Over the course of one year, she had two discrete two hour long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. While the etiology of accelerated long term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep-related seizures may contribute, and highlight the importance of video-EEG monitoring. This article is protected by copyright. All rights reserved.

Summary Objective To determine the outcome of implanting fewer electrodes over the hemisphere with less supporting presurgical localizing data. Methods We retrospectively reviewed our epilepsy surgery database at Mayo Clinic, Rochester, Minnesota, between January 1, 1999, and December 31, 2011, to identify patients who had an asymmetric number of electrode contacts implanted in each hemisphere for seizure localization. We scored each presurgical noninvasive data point (0, 0.5, or 1) to predict the likelihood of identifying seizure onset in the hemisphere with fewer intracranial electrode contacts (HFEC). An aggregate score was obtained for each patient. Results Thirteen (37%) of 35 patients had HFEC-onset seizures on intracranial electroencephalography (iEEG). The following factors predicted HFEC-onset seizures: (1) temporal lobe epilepsy (p = 0.02); (2) interictal scalp electroencephalographic discharges at the HFEC (p = 0.04); and (3) both interictal and ictal scalp EEG discharges at the HFEC (p = 0.01). The median (range) aggregate score was 2 (1–3) for patients with HFEC-onset seizures recorded on iEEG and 1 (0–3) for patients without HFEC-onset seizures (p = 0.001). Using this scoring model, the odds ratio of identifying HFEC-onset seizures on iEEG was 6.4 for each one-point increment in the aggregate score. The area under the receiver operating characteristic curve for this model was 0.84, suggesting excellent ability of the aggregate score to discriminate between patients with and without HFEC-onset seizures on iEEG. Significance Implanting electrodes on the basis of limited supporting presurgical data may be useful in selected patients, especially those with temporal lobe epilepsy, interictal scalp discharges involving the HFEC, or both interictal and ictal scalp discharges involving the HFEC. In addition, our proposed scoring system may be helpful in selecting patients with complicated epilepsy for implantation of an asymmetric number of intracranial electrodes in the hemispheres.

SUMMARY Purpose: To evaluate long-term seizure outcome in children with epilepsy and a focal or hemispheric neuroimaging abnormality. Methods: All children (

Partial seizure disorders account for the majority of epilepsy (Sander et al., 1990). In one tertiary center cohort of 2,200 patients, partial epilepsy was more than twice as common as symptomatic, cryptogenic, and idiopathic generalized epilepsies combined. Moreover, in that study, two-thirds of the partial seizure disorders localized to the temporal lobe (Semah et al., 1998). Unfortunately, despite optimal medical therapy, approximately 30% of patients continue to experience recurrent seizures (Sander et al., 1990 Wiebe, et al. 2001). In a recent well-designed trial studying patients who failed initial medication trials, seizure freedom was achieved in only 8% of patients with continued medical therapy compared to 58% of patients undergoing anterior temporal lobectomy (Wiebe, et al. 2001). However, physicians may be reluctant to consider surgery for temporal lobe epilepsy when structural neuroimaging appears normal. Temporal lobectomy has been shown to render about 80% of patients seizure-free in the setting of a magnetic resonance imaging (MRI)–apparent structural abnormality concordant to the seizure onset zone, such as mesial temporal sclerosis (MTS) (Cascino, 2004). On the other hand, patients with temporal lobe epilepsy and normal MRI have received less attention. In order to demonstrate the absence of a potentially epileptogenic structural lesion, it is critical that patients have high-resolution seizure protocol MRI with both T1- and T2-weighted images (Jack, 1996; Cascino, 2004). There are relatively few studies examining temporal lobectomy in patients with normal modern seizure protocol MRI. Existing research suggests significantly disparate rates of successful surgery in patients with nonlesional MRI, ranging from 18–63% of patients becoming seizure-free (Berkovic et al., 1995; Theodore et al., 1997; Sylaja et al., 2004; Cohen-Gadol et al., 2005; Jeha et al., 2006). Many of these studies were conducted during the 1980s and early 1990s (Berkovic et al., 1995; Radhakrishnan et al., 1998; McIntosh et al., 2004), prior to the widespread use of epilepsy neuroimaging protocols that are more sensitive for detecting MTS (Jack, 1996; Jack et al., 1996). Some of these studies used pathologic findings to categorize patients (McIntosh et al., 2004; Cohen-Gadol et al., 2006), information that is not available preoperatively for clinical prognostication. Other studies include heterogeneous patient populations and only small numbers of patients with nonlesional MRI (Holmes et al., 2000; Sylaja et al., 2004; Cohen-Gadol et al., 2005). Therefore, we sought to examine the efficacy of epilepsy surgery and noninvasive predictors of favorable outcome for patients with medically refractory temporal lobe epilepsy and a nonlesional high-resolution seizure protocol MRI.

Summary Purpose: To compare mortality and subsequent unprovoked seizure risk in a population-based study of acute symptomatic seizure and first unprovoked seizure due to static brain lesions. Methods: We ascertained all first episodes of acute symptomatic seizure and unprovoked seizure due to central nervous system (CNS) infection, stroke, and traumatic brain injury (TBI). Subjects were residents of Rochester, Minnesota, identified through the Rochester Epidemiology Project’s records-linkage system between 1/1/55 and 12/31/84. Information was collected on age, gender, seizure type, etiology, status epilepticus (SE), 30-day and 10-year mortality, and subsequent episodes of unprovoked seizure. Results: Two hundred sixty-two individuals experienced a first acute symptomatic seizure and 148 individuals experienced a first unprovoked seizure, all due to static brain lesions. Individuals with a first acute symptomatic seizure were 8.9 times more likely to die within 30 days compared to those with a first unprovoked seizure [95% confidence intervals (CI) = 3.5–22.5] after adjustment for age, gender, and SE. Among 30-day survivors, the risk of 10-year mortality did not differ. Over the 10-year period, individuals with a first acute symptomatic seizure were 80% less likely to experience a subsequent unprovoked seizure compared with individuals with a first unprovoked seizure [adjusted rate ratio (RR) = 0.2, 95% CI = 0.2–0.4]. Discussion: The prognosis of first acute symptomatic seizures differs from that of first unprovoked seizure when the etiology is stroke, TBI, and CNS infection. Acute symptomatic seizures have a higher early mortality and a lower risk for subsequent unprovoked seizure. These differences argue against the inclusion of acute symptomatic seizures as epilepsy.

Summary: Purpose: To determine the extent to which periictal subtraction single-photon emission computed tomography (SPECT) may improve detection and definition of the epileptogenic zone in patients with focal malformations of cortical development (MCDs). Methods: Subtraction SPECT coregistered to magnetic resonance (MR) images (SISCOM) were constructed for 22 consecutive patients with focal MCDs who underwent periictal SPECT injection (18 ictal and four postictal). In the 17 patients who had epilepsy surgery, concordance between the site of SISCOM localization and site of surgical resection was determined by coregistration of SISCOM images with postoperative MRIs. Results: SISCOM images were localizing in 19 (86%) patients, including eight of the 10 with nonlocalizing MRI. Concordance of SISCOM localization was 91% with MRI localization, 93% with scalp ictal EEG localization, and 100% with intracranial EEG localization. Eight patients whose SISCOM localization was concordant with the surgical resection site had lower postoperative seizure frequency scores (SFSs; p = 0.04) and greater postoperative improvement in SFSs (p = 0.05) than the nine patients whose SISCOM was either nonconcordant or nonlocalizing. On multiple regression analysis, a model combining SISCOM concordance with surgical resection site and extent of MRI lesion resection was predictive of postoperative SFS (R2= 0.47; p = 0.03). Conclusions: Periictal subtraction SPECT using the SISCOM technique provides useful information for seizure localization in patients with focal MCDs, even when MRI is nonlocalizing.

Summary: Purpose: To evaluate the incidence and prognostic importance of acute postoperative seizures (APOSs) occurring in the first week after a focal corticectomy in patients with partial epilepsy of frontal lobe origin. Methods: We retrospectively evaluated 65 patients who underwent a frontal lobe cortical resection for intractable partial epilepsy between April 1987 and December 2000. All patients were followed up for a minimum of 1 year after surgery. Results: APOSs occurred in 17 (26%) patients. None of the following factors was shown to be significantly associated with the occurrence of APOSs: gender, duration of epilepsy, etiology for seizure disorder, use of subdural or depth electrodes, surgical pathology, or postoperative risk factor for seizures. Patients with APOSs were older at seizure onset and at the time of surgery (p = 0.003 and p = 0.05, respectively). At last follow-up, patients who had APOSs had a seizure-free outcome similar to that of individuals without APOSs (47.1% vs. 50.0%; p = 0.77). Patients with APOSs appeared less likely to have a favorable outcome [i.e., fewer than three seizures per year and >95% decrease in seizure activity (58.8 vs. 70.8%; p = 0.35)]. This result may not have reached statistical significance because of the sample size. No evidence suggested that precipitating factors or the timing of APOSs was an important prognostic factor. Conclusions: The presence of APOSs after frontal lobe surgery for intractable epilepsy does not preclude a significant reduction in seizure tendency. These findings may be useful in counseling patients who undergo surgical treatment for frontal lobe epilepsy.

Summary: Purpose: To determine whether a focal β-frequency discharge at seizure onset on scalp EEG predicts outcome of frontal lobe epilepsy (FLE) surgery. Methods: We identified 54 consecutive patients with intractable FLE who underwent epilepsy surgery between December 1987 and December 1996. A blind review of EEGs and magnetic resonance images (MRIs) was performed. Lesional epilepsy is defined as presence of an underlying structural abnormality on MRI. Results: Overall, 28 (52%) patients were seizure free, with a mean follow-up of 46.5 months. Presence of a focal β-frequency discharge at seizure onset on scalp EEG predicted seizure-free outcome in lesional (p = 0.02) and nonlesional (p = 0.01) epilepsy patients. At least 90% of patients who had either lesional or nonlesional epilepsy were seizure free if scalp EEG revealed a focal β discharge at ictal onset. Moreover, logistic regression analysis showed that focal ictal β pattern and completeness of lesion resection were independently predictive of seizure-free outcome. Ictal onset with lateralized EEG activity of any kind and postresection electrocorticographic spikes did not predict surgical outcome (p > 0.05). Conclusions: Only about 25% of FLE surgical patients have a focal β-frequency discharge at seizure onset on scalp EEG. However, its presence is highly predictive of excellent postsurgical seizure control in either lesional or nonlesional FLE surgical patients.

Purpose: High-dose i.v. opioids (e.g., alfentanil, 50 μg/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 ≤0. 1% (end-tidal) in 50% N 2 O, and i.v. fentanyl, 2 μg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 μg/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 ≤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 '5 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.

A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31-0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1-1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent manner. Chlorthiazide's toxic dose for 50% of animals tested (TD 50 ) could not be achieved even with dosing as high as 1,500mg/kg for furosemide; TD 50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.

We tested the hypothesis that major depression meeting DSM-III-R criteria or medical therapies for depression increase the risk for unprovoked seizures. Major depression was associated with a sixfold increased risk for unprovoked seizures (95% CI, 1.56-22). The risk remained increased even when controlling for age, sex, length of medical follow-up, and medical therapies for depression. In the absence of known prior neurological insult, major depression is associated with an increased risk for unprovoked seizures.

We asked whether acute symptomatic status epilepticus (SE) increases the risk for subsequent unprovoked seizure compared with less prolonged acute symptomatic seizure. We also explored whether the risk of unprovoked seizure differs by cause. We ascertained all first episodes of acute symptomatic seizure among residents of Rochester, Minnesota, through the Rochester Project's records-linkage system. Information was collected on seizure duration, age, sex, cause, and subsequent unprovoked seizure. At 10 years of follow-up, the risk of unprovoked seizure was 41% for those with acute symptomatic seizure with SE and 13% for those without SE. Controlling for age, sex, and cause, SE increased the risk for subsequent unprovoked seizure 3.3-fold (95% confidence interval, 1.8-6.1) compared with brief acute symptomatic seizures. Among patients with SE, the risk of unprovoked seizure was increased 18.8-fold for patients with anoxic encephalopathy, 7.1-fold for patients with a structural cause, 3.6-fold for patients with a metabolic cause. The increased risk for unprovoked seizure after SE compared with shorter seizures may be due to SE being a marker for severity of injury, damage caused by SE, or a biological substrate associated with the tendency to experience SE.

Summary: Purpose: To evaluate the diagnostic yield and identify predictive factors of the surgical outcome in patients with intractable partial epilepsy undergoing chronic intracranial EEG monitoring (CIEM). Methods: The clinical, magnetic resonance imaging (MRI) and electrophysiologic data of 108 patients that underwent CIEM were retrospectively reviewed. The discharge pattern and spatial extent of the initial ictal discharge were determined by blinded visual inspection and computerized analysis. Results: The main predictive indicator for epilepsy surgery outcome in patients that underwent CIEM was the presurgical MRI findings. Most patients with hippocampal atrophy or complete lesionectomy were rendered seizure free after epilepsy surgery (83 and 80%, respectively), whereas only a small minority of patients with partial lesipectomy or no detected MRI lesion had seizure-free operative outcomes (21 and 22%, respectively). Multifocal independent initiation of the initial ictal discharge was associated with a poor surgical outcome. In contrast, the pattern and local spatial extent of the initial ictal discharge observed with CIEM failed to predict the surgical outcome. Conclusions: The main predictor of the surgical outcome in patients that underwent CIEM was the MRI findings, whereas CIEM had only limited use in localizing the epileptogenic zone in the absence of an MRI lesion. The reported findings indicate a low specificity of CIEM in defining the site of seizure onset, which in turn significantly impairs the reliability of CIEM in delineating the epileptogenic zone for epilepsy surgery. Further studies are required to define the indications and patient subpopulations who can benefit from CIEM before epilepsy surgery. Key Words: Epilepsy-Intracranial electrodesEpilepsy surgery-EEG-Hippocampal atrophy.

Summary: Purpose: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE. Methods: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1,1965 and December 31, 1984, we studied all first episodes of a febrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996). Results: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with non febrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2–0.9). No effect of duration or seizure type was shown after adjusting for other risk factors. Conclusions: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.

Summary: Objective: In the last decade several studies have been published on incidence, etiology, and prognosis of status epilepticus (SE) with population-based data from the United States and Europe. The aim of this review is to summarize the available information on the epidemiology of SE and to outline the sources of the variability in reported mortality after SE. Methods: Comparison of mortality studies in SE from the United States and Europe. Results: The incidence of SE is lower in Europe (9.9‐ 15.8/10,000) than in the United States (18.3‐41/100,000). The overall mortality after SE is similar in the two U.S. studies: the case fatality is 21% in Rochester, and 22% in Richmond. All European studies excluded SE after anoxic encephalopathy following cardiac arrest. This exclusion may partly explain the lower case fatality (around 10%) found in two of the European studies. The study from Bologna showed the highest case fatality (33%) even after exclusion of anoxic encephalopathy. The mortality in acute symptomatic SE was higher than for other forms of SE across all studies. Conclusions: Short-term mortality after SE occurs mainly in the acute symptomatic group. Based on published data, it is not clear if differences in early management and medical treatment have any impact on prognosis or whether the differences can be attributed only to differences in distribution of the underlying causes in acute symptomatic SE. Future studies should address this issue. Ke yW ords: Status epilepticus—Mortality— Prognosis. Status epilepticus (SE), usually defined as a seizure lasting at least 30 min, is considered a medical emergency. It occurs most frequently in the context of an acute systemic or neurological insult and less frequently in patients with epilepsy. There have been many published studies regarding mortality after SE, most of which are based on clinical series from tertiary care centers. The reported mortality varies from 7% to 46% (1‐15).

Summary: Purpose: Ictal single-photon emission computed tomography (SPECT) may be a reliable indicator of the ictal onset zone in patients with intractable partial epilepsy who are being considered for epilepsy surgery. The rationale for the illustrated case report is to evaluate the use of an innovation in SPECT imaging in a patient with nonlesional extratemporal epilepsy. Methods: We investigated the presurgical evaluation and operative outcome in a patient with intractable partial epilepsy. The ictal semiology indicated a “hypermotor” seizure with bipedal automatism. The electroclinical correlation and magnetic resonance imaging (MRI) did not suggest the appropriate localization of the epileptogenic zone. A subtraction periictal SPECT coregistered to MRI (SISCOM) was peformed. Results: SISCOM revealed a region of localized hyperperfusion in the right supplementary sensorimotor area. Chronic intracranial EEG monitoring confirmed the relationship between the localized SISCOM alteration and the ictal onset zone. The patient was rendered seizure free after surgical treatment. Conclusions: SISCOM may be used to identify potential candidates for surgical treatment of nonlesional extratemporal epilepsy. Periictal imaging may also alter the strategy for intracranial EEG recordings and focal cortical resection.

Neuroimaging has significantly altered the management of patients with partial epilepsy. Magnetic resonance imaging (MRI) has been demonstrated to be a reliable and accurate indicator of the common pathologic findings underlying a partial seizure disorder. Intracranial mass lesions have been shown to be highly coherent with the localization of the epileptogenic zone. An MRI-identified epileptogenic lesion affects the selection of patients for epilepsy surgery and alters the diagnostic evaluation and the operative strategy. The results of the MRI preoperatively have prognostic importance in patients undergoing surgical treatment for partial epilepsy. Patients with lesional epileptic syndromes are considered favorable candidates for surgical ablative treatment. Hippocampal volume studies may predict the neurocognitive outcome in patients undergoing temporal lobe surgery. The use of MRI has resulted in a reduction in chronic intracranial EEG monitoring at most epilepsy centers, especially in patients with lesional pathology. MRI may be a reasonable initial "screening" procedure in selected patients with intractable partial epilepsy before consideration of a presurgical evaluation. A classification of partial epilepsy is proposed, based on the results of MRI, that may be useful for patients being considered for surgical treatment. Importantly, preoperative MRI must be correlated with the electrophysiologic studies and ictal semiology before decision-making regarding surgical therapy.

We performed a retrospective study of 51 consecutive patients who underwent operation for intractable partial epilepsy related to low-grade intracerebral neoplasms between 1984 and 1990. All patients had medically refractory partial seizures and a mass lesion identified on neuroimaging studies. Lesionectomy was performed on 17 patients, and 34 had lesion resection and corticectomy. Mean postoperative follow-up was 4.4 years (range 2-8 years). Sixty-six percent of patients were seizure-free, and 88% experienced a significant reduction in seizure frequency. In 16 patients (31%), antiepileptic drugs (AEDs) were successfully discontinued. Twenty-five of 31 (81%) eligible patients obtained a driver's license after successful operation. Patients with complete tumor resection and no interictal epileptiform activity on postoperative EEG studies had the best operative outcome. Epilepsy surgery can result in long-term improvement in seizure control and quality of life (QOL) in selected patients with intractable tumor-related epilepsy. Our results should be useful to clinicians considering treatment options for patients with intractable seizures related to low-grade intracerebral neoplasms.

Fifty patients with medically refractory extratemporal seizures underwent epilepsy surgery at our institution between 1988 and 1992. Twenty-nine patients (group I) had an extratemporal (mainly frontal lobe) corticectomy, and 21 patients (group II) had an epileptogenic lesion extirpated without resection of the epileptic brain tissue. Comprehensive neurologic evaluation was performed preoperatively, soon after operation, and approximately 3 months postoperatively to assess operative outcome. Magnetic resonance imaging (MRI) in group I patients usually showed no abnormality or a large destructive lesion. Neuroimaging showed a foreign tissue lesion in most group II patients. Thirteen of the 29 patients who underwent corticectomy had at least one adverse event (AE) potentially related to operation at the time of initial assessment. Four of the 13 patients required a surgical procedure to treat the operative complication, but only 1 of the 13 patients had a persistent neurologic deficit at follow-up examination. Three of the 21 patients who received lesionectomy had acute and persistent neurologic morbidity. Patients undergoing cortical resection remained intubated longer postoperatively (p < 0.005), and required longer hospitalization after operation (p < 0.001) and in the intensive care unit (p < 0.001) as compared with the lesionectomy group. Results of this study may prove useful in counseling patients regarding neurologic outcome after extratemporal surgery.

Nonconvulsive status epilepticus (SE) accounts for approximately one-quarter of all cases of SE. The actual proportion may be higher because patients with nonconvulsive SE may go unidentified. This disorder may be divided into generalized (absence) or partial (complex partial) forms. Nonconvulsive SE may occur de novo or in patients with epilepsy. Absence SE is considered more frequent and is characterized by a continuous neurocognitive alteration. Complex partial SE may be associated with recurrent seizure activity and a cycling of the clinical states. Treatment includes antiepileptic drug(s) (AEDs) and avoidance of seizure precipitants. Electrophysiological studies are necessary to confirm the diagnosis of nonconvulsive SE and to monitor the response to AED therapy. Prompt recognition and treatment may be necessary to avoid neurological morbidity in select patients. Epilepsy with continuous spikes and waves during slow sleep (ESES) and the Landau-Kleffner syndrome are two rare childhood disorders that are difficult to classify but may be appropriate to include in a discussion of nonconvulsive SE.

We performed an extended follow-up study assessing the efficacy of stereotactic lesionectomy in 23 patients with foreign-tissue lesions and intractable partial epilepsy. Sixteen lesions involved functional or eloquent cortex as determined by anatomic localization. By definition, the surgical objective in these patients was excision of the lesion, and not the surrounding cerebral cortex. The mean duration of follow-up was 48.5 months (range 26-69 months). Seventeen patients (74%) had a significant reduction in seizures (greater than or equal to 90%) after lesionectomy. Thirteen patients (56%) had a class I operative outcome (seizure-free, single seizure episode, or auras only). Five of these patients were successfully discontinued from antiepileptic drug (AED) therapy. Patients with temporal lobe lesions were statistically less likely to be rendered seizure-free (p less than 0.05). Age at operation, duration of epilepsy, and underlying pathology were not significant predictors of seizure outcome. The anatomic distribution of extracranial EEG recorded epileptiform activity did not appear to be an important determinant of outcome. The absence of interictal epileptiform activity in the 3-month postoperative EEG correlated with a significant reduction in seizures. Long-term follow-up indicates that lesionectomy may be effective in select patients with medically refractory partial seizure disorders.

We developed a magnetic resonance imaging (MRI)–based technique for measuring the volume of the hippocampal formation. In this study, the relationship between volumes of the hippocampal formation and outcome (i.e., postoperative seizure control) after anterior temporal lobectomy for intractable epilepsy was analyzed in 50 consecutive patients in whom the surgical specimen did not contain an epileptogenic mass lesion. Outcome was classified as either satisfactory or unsatisfactory. A significant relationship was found between outcome and volume of the operated of hippocampal formation (p = 0.012), as well as a derived volumetric measure (nonoperated minus operated volume of the hippocampal formation) (p = 0.004). The association between outcome and nonoperated volume was borderline (p = 0.057). Thirty-four (97%) of 35 patients in whom the volumetric study and electroencephalography (EEG) concordantly lateralized the seizure disorder had satisfactory postoperative seizure control. Conversely, only 7 (42%) of 12 patients in whom the volume study was nonlateralizing and 1 (33%) of 3 in whom the EEG and volume study were discordant had a satisfactory outcome. We regard our MRI-based study of hippocampal formation volume as a noninvasive surrogate for the identification of moderate or severe mesial temporal sclerosis. The technique is a useful adjunct in a multidisciplinary, preoperative epilepsy evaluation when T2-weighted MRIs do not reveal an epileptogenic mass lesion. The reasons for the usefulness of this imaging technique are: (1) It is an independent source of information on seizure lateralization, (2) it will provide information as to expected postoperative outcome, and (3) it may aid in appropriately selecting patients for invasive preoperative monitoring studies.

The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy. The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer. In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region. In nonepileptic senescent primates, occasional very sparse supragranuler Timm granules were observed that were easily distinguished from the dense pattern observed in association with human epilepsy. The results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy.