bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Clobazam and Its Active Metabolite on GABA‐Activated Currents in Rat Cerebral Neurons in Culture
Authors: Nakamura Fumihiro , Suzuki Setsuo , Nishimura Shigeko , Yagi Kazuichi , Seino Masakazu
Published: August 2005

Summary: Purpose: The antiepileptic effects of clobazam, a 1,5‐benzodiazepine, have been well documented in animal experiments and clinical trials. However, the drug's mechanisms of antiepileptic actions are still undetermined. The purpose of this study was to learn how clobazam and its active metabolite modulate γ‐aminobutyric acid (GABA)‐activated currents in rat cerebral neurons in culture.

Methods: Whole‐cell voltage‐clamp recordings were performed on cultured cerebral neurons of the rat. Clobazam or its metabolite N‐desmethylclobazam was dissolved in the extracellular solution and applied for 2 s by pressure ejection from a micropipette. To maintain GABA‐activated currents, 2 mM Mg adenosine triphosphate (ATP) was added to the intracellular solution.

Results: GABA elicited outward currents that were mediated by GABAA receptor‐coupled Cl‐ channels. Applying clobazam with 10 μM GABA elicited enhanced outward currents. Flumazenil, an antagonist of the benzodiazepine receptor, inhibited the enhancing effect of clobazam. The enhancement ratio increased as much as 2.28‐fold in a dose‐dependent manner at a concentration of 3 μM clobazam. However, it started to decrease at a concentration of 10 μM clobazam. The metabolite N‐desmethylclobazam was tested in the same manner, and exhibited an identical dose‐dependent enhancement of GABA‐activated currents.

Conclusions: The antiepileptic effects of the 1,5‐ benzodiazepines are attributed to the enhancement of GABAergic inhibitory neurotransmission. The antiepileptic effects of clobazam are thought to depend mainly on its active metabolite N‐desmethylclobazam, which is present in high concentrations in patients who receive long‐term clobazam. Clobazam's enhancement of GABAactivated currents was most marked on weaker GABA currents. We therefore infer that clobazam acts more efficiently on tissues in which the release of GABA is diminished.
Severe, Uncontrolled Hypertension and Adult‐Onset Seizures: A Case‐Control Study in Rochester, Minnesota
Authors: Hesdorffer D. C. , Hauser W. A. , Annegers J. F. , Rocca W. A.
Published: August 2005

Summary: Purpose: Hypertension is an established risk factor for clinically detected stroke, which is in turn a risk factor for epilepsy. This relation suggested that hypertension, particularly severe and uncontrolled, might increase the risk of epilepsy in the absence of prior clinically detected stroke.

Methods: Subjects in this population‐based case‐control study were the 145 incident cases of first unprovoked seizure aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow‐up. Using the records‐linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, all blood pressure readings before each case's first seizure came to medical attention. Subjects were classified as hypertensive if they had at least two readings of 160/95 mm Hg or if there was electrocardiographic evidence for left ventricular hypertrophy.

Results: Severe uncontrolled hypertension increased the risk of unprovoked seizure. Left ventricular hypertrophy without diuretic treatment was associated with an 11‐fold increased risk of unprovoked seizure: left ventricular hypertrophy treated with diuretics did not increase the risk.

Conclusions: In the absence of clinically detected stroke, left ventricular hypertrophy without diuretic use may increase the risk of unprovoked seizures, and diuretic treatment may protect against this increased risk.
Study of Psychiatric Symptoms after Discontinuation of Antiepileptic Drugs
Authors: Kubagawa Tetsuji , Furusho Junichi , Maruyama Hiroshi
Published: August 2005

Summary: We studied 23 patients with epilepsy and a hallucinatory delusional state (group A) or other psychotic symptoms (group B) in whom antiepileptic drugs (AEDs) were successfully discontinued. Patients in group A had an earlier age at onset of both epilepsy and psychotic symptoms than those in group B. Both groups had similar seizure frequency and duration of AED therapy. The psychotic symptoms in group A patients started at the age 20.8 years and lasted longer than in group B patients; and antipsychotic drug treatment was generally effective, but the social adaptation (work/personal life) of the patients was poor. We considered that group A patients had schizophrenia rather than mere recurrence of epileptic psychosis.
Dipole Modeling in Epilepsy Surgery Candidates
Authors: Boon P. , D'Havé M. , Adam C. , Vonck K. , Baulac M. , Vandekerckhove T. , Reuck J. De
Published: August 2005

Summary: Purpose: The validity and clinical significance of dipole modeling in epilepsy surgery candidates is not fully established.

Patients and Methods: Interictal and ictal dipole modeling was performed in 43 patients with refractory complex partial seizures (CPS) and intracranial structural abnormalities demonstrated with optimum magnetic resonance imaging (MRI: space–occupying, n = 15; atrophic, n = 26; dysplastic, n = 2). Video–EEG monitoring showed CPS in all patients. In 12 patients, additional intracranial EEG monitoring demonstrated hippocampal seizure onset in 11 patients and medial occipital ictal onset in 1.

Results: Spatiotemporal dipole mapping of averaged interictal spikes and epochs of early ictal discharges revealed two distinct dipole patterns. Patients with lesions located in the medial (± lateral) temporal lobe (n = 34) and medial occipital lobe (n = 1) uniformly presented a combined interictal dipole that consisted of a radial and a tangential component with a high degree of elevation relative to the axial plane. Eight of 9 patients with extratemporal lesions had a less stable dipole with a predominant radial component. Ictal dipole modeling identified the ictal onset zone correctly as compared with intracranial EEG recordings from bilateral hippocampal depth electrodes. Ictal dipoles showed a striking correspondence with the interictal dipoles in individual patients.

Conclusions: Interictal and ictal dipole mapping provided additional, reliable, and relevant localizing information in surgical candidates for refractory CPS. Ictal dipole analysis may limit the number of patients who require intracranial electrodes.
A Comparison Between One and Three Years of Treatment in Uncomplicated Childhood Epilepsy: A Prospective Study. II. The EEG as Predictor of Outcome After Withdrawal of Treatment
Authors: Andersson Thomas , Braathen Gunnar , Persson Anders , Theorell Klas
Published: August 2005

Summary: Purpose: We wished to evaluate the prognostic usefulness of various EEG parameters with respect to remission rates after discontinuation of antiepileptic drug (AED) therapy in children treated for epileptic seizures.

Methods: Two hundred forty‐four children with uncomplicated epileptic seizures were randomized to either 1 or 3 years of treatment with AEDs. The treatment was then discontinued in patients who had been seizure‐free during the last 6 months of their allotted time of treatment (n = 154). After treatment discontinuation, the children were followed for at least 2 years. EEG recordings were performed before treatment was initiated and at regular intervals during treatment.

Results: The overall relapse rate was 37%. In many children, the amount of epileptiform activity varied considerably between subsequent recordings made during the treatment. The remission rate was slightly higher for children whose last recordings before AED discontinuation were free of epileptiform activity as compared with children in whom such activity was present. However, children who had irregular generalized spike–wave (SW) activity in the recordings made before discontinuation of treatment had a clearly higher relapse rate (67%) both as compared with children without epileptiform activity (33%) and as compared with children with other types of epileptiform activity (33%) in their last EEG recordings before discontinuation. All children treated for only 1 year whose final EEGs displayed generalized irregular SW activity relapsed.

Conclusions: We conglude that the presence of epileptiform activity does not in itself necessarily influence prognosis after discontinuation of treatment but that certain types of such activity signal a high risk of relapse.
Cortical and Hippocampal Volume Deficits in Temporal Lobe Epilepsy
Authors: Marsh Laura , Morrell Martha J. , Shear Paula K. , Sullivan Edith V. , Freeman Hope , Marie Ariane , Lim Kelvin O. , Pfefferbaum Adolf
Published: August 2005

Summary: Purpose: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization‐related epilepsy of temporal lobe origin (TLE).

Methods: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3–mm spin‐echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range‐matched controls were examined with analysis of variance (ANOVA).

Results: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.

Conclusions: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra‐temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.
What is the Relationship Between Arachnoid Cysts and Seizure Foci?
Authors: Arroyo Santiago , Santamaria Joan
Published: August 2005

Summary: Purpose: Arachnoid cysts are sometimes encountered in MRIs performed for a variety of reasons. In patients with epilepsy, particularly those with refractory epilepsy, arachnoid cysts are often assumed to be related to their seizure focus. We conducted a study to investigate this putative relationship.

Methods: A retrospective study on the incidence of arachnoid cysts was performed in patients seen in our Epilepsy Clinic who had CT or MRI scans, interictal EEGs or ictal EEGS. Locations of seizure foci in these patients were defined from clinical and electrophysiologic data.

Results: Seventeen of 867 patients had arachnoid cysts. Twelve patients had temporal lobe cysts and only 3 of them had temporal lobe seizures. Four patients had frontal lobe cysts and only 1 had frontal lobe seizures ipsilateral to the cyst. One patient had a cerebellopontine angle cyst and frontal lobe seizures. Thus, clinical manifestations of seizures and EEG findings (interictal and/or ictal) indicated that the seizure focus was adjacent to the cysts in only 4 patients (23.5%).

Conclusions: Our findings suggest that arachnoid cysts are often an incidental finding in patients with epilepsy and do not necessarily reflect the location of the seizure focus.
Continuous Source Imaging of Scalp Ictal Rhythms in Temporal Lobe Epilepsy
Authors: Assaf Bassam A. , Ebersole John S.
Published: August 2005

Summary: Purpose: We wished to determine whether continuous EEG source imaging can predict the location of seizure onset with sublobar accuracy in temporal lobe epilepsy (TLE).

Methods: We retrospectively analyzed the earliest scalp ictal rhythms, recorded with 23‐ to 27‐channel EEG, in 40 patients with intractable TLE. A continuous source analysis technique with multiple fixed dipoles (Focus 1.1) decomposed the EEG into source components representing the activity of major cortical sublobar surfaces. For the temporal lobe, these were basal, anterior tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized according to its most prominent and leading source component. All patients underwent intracranial EEG studies before epilepsy surgery, and all had a successful surgical outcome (follow‐up >1 year).

Results: Most patients with ictal rhythms having a predominant basal source component had hippocampal‐onset seizures, whereas those with seizures with prominent lateral source activity had predominantly temporal neocortical seizure origins. Seizures with a prominent anterior temporal tip source component mostly had onset in entorhinal cortex. Seizures in some patients had several equally large and nearly synchronous source components. These seizures, which could be modeled equally well by a single oblique dipole, had onset predominantly in either entorhinal or lateral temporal cortex.

Conclusions: Multiple fixed dipole analysis of scalp EEG can provide information about the origin of temporal lobe seizures that is useful in presurgical planning. In particular, it can reliably distinguish seizures of mesial temporal origin from those of lateral temporal origin.
Periventricular Nodular Heterotopia: Epileptogenic Findings
Authors: Battaglia Giorgio , Granata Tiziana , Farina Laura , D'Incerti Ludovico , Franceschetti Silvana , Avanzini Giuliano
Published: August 2005

Summary: Purpose: We studied 17 patients with periventricular nodular heterotopia (PNH) to further investigate the electroclinical pictures and semiology of the associated seizures.

Methods: PNH was diagnosed by means of magnetic resonance imaging (MRI). The patients’ clinical and familial histories were carefully analyzed, and their electroclinical features and course of epilepsy followed for periods ranging from 10 months to 22 years. The electroclinical data were compared with those of previously reported PNH cases.

Results: The patients were subdivided into those with bilateral (7) and unilateral (10) PNH. The former were mainly characterized by structural abnormalities in the posterior cerebral fossa and multiple seizure types; the latter were characterized by the paratrigonal location of the malformation and, frequently, by elementary seizures with a visual or auditory onset. Focal seizures were drug resistant in most cases. The interictal EEG abnormalities were always focal and consistent with the location of the PNH. A previously unreported photic driving of posterior background activity was observed in all patients and was always consistent with the PNH location.

Conclusions: Conclusions: Our present findings and previously reported data show that bilateral and unilateral PNH cases are different in their morphological and electroclinical features and may be determined by different etiologies. The female predominance, frequent familial occurrence, and positive family history for epilepsy suggest that genetic factors may be involved in the genesis of bilateral and symmetrical PNH, whereas the presence of prenatal risk factors and its location in the watershed paratrigonal area suggest that vascular mechanisms may determine unilateral PNH.
Social Adjustment and Competence 35 Years After Onset of Childhood Epilepsy: A Prospective Controlled Study
Authors: Jalava Merja , Sillanpää Matti , Camfield Carol , Camfield Peter
Published: August 2005

Summary:Purpose:To study the effect of childhood‐onset epilepsy without other neurologic deficit on adult social adjustment and competence.

Methods:Social competence was studied in a prospective, population‐based cohort of childhood‐onset epilepsy after a mean follow‐up of 35 years. One hundred patients (60% of the total cohort) had no other neurologic problems (“epilepsy only”), and for each patient, two matched controls, a “random” control and an “employee” control were chosen.

Results:Good social outcome was significantly reduced in the “epilepsy only” cohort compared with random controls: education [cumulative odds ratio (COR), 2.4; 95% confidence interval (CI), 1.4–4.11; employability (COR, 7.3; 95% CI, 2.7–20.0); and marriage rate (COR, 3.7; 95% CI, 1.9–7.3). The patients with epilepsy rated their own ability to control their lives as “poor or missing” four times more frequently than the employee controls. Patients receiving antiepileptic polytherapy, but not monotherapy, were significantly less satisfied with their present life (OR, 6.7; 95% CI, 1.9–24.1) and felt their general health was significantly poorer (OR, 5.1; 95% CI, 1.2–21.3) than did the employee controls. Furthermore, patients with continuing seizures were significantly less satisfied with their present life (OR, 4.1; 95% CI, 1.1–15.1) than were employee controls.

Conclusions:Many patients with “epilepsy only” beginning in childhood have persistent and significant social‐adjustment and competence problems in adulthood.
Persistent Nonconvulsive Status Epilepticus After the Control of Convulsive Status Epilepticus
Authors: DeLorenzo R. J. , Waterhouse E. J. , Towne A. R. , Boggs J. G. , KO D. , DeLorenzo G. A. , Brown A. , Garnett L.
Published: August 2005

Summary: Purpose: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures.

Methods: One hundred sixty‐four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected.

Results: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after‐SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported.

Conclusions: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.
Evidence of Late‐Onset Infantile Spasms
Authors: Bednarek N. , Motte J. , Soufflet C. , Plouin P. , Dulac O.
Published: August 2005

Summary: Purpose: To underline the unusual but possible Occurrence of epileptic spasms (ES) in children >1 year of age.

Methods: Cases in whom onset of spasms occurred after 1 year of age were identified through a retrospective review of the records of all patients referred for ES to the Saint‐Vincent de Paul Hôpital (Paris) and American Memorial Hospital (Reims) between 1974 and 1994.

Results: Eighteen cases were identified among the 734 children referred for ES, 18 cases were identified where spasm onset time ranged from 12 to 38 months of age. In 1/3 of the cases, the diagnosis was suspected from the onset of clinical manifestations; in the remaining 2/3, diagnosis was delayed by a mean 6 months (range, 2–25 months). Neurobehavioral regression affected two‐thirds of the patients. Modified hypsarrhythmia was present in 11 patients; all but one exhibited major and diffuse spike‐ and slow‐wave activity. EEG abnormalities were detected in the frontal areas in 11 patients. Spasms were cryptogenic in 9 patients. Steroids were administered to 13 patients; these controlled the spasms in 6 patients. Outcome was favorable for both seizures; cognition favorable in only 2 of the 18 patients.

Conclusions: Beginning after the first year of life, ES, or late‐onset infantile spasms, are distinct from early Lennox‐Gastaut syndrome, although etiology, prognosis and treatment are similar to that for the classical infantile spasms.
Development and Cross‐Cultural Translations of a 31‐Item Quality of Life in Epilepsy Inventory
Authors: Cramer Joyce A. , Perrine Kenneth , Devinsky Orrin , Bryant‐Comstock Lynda , Meador Kimford , Hermann Bruce
Published: August 2005

Summary: Purpose: We report the development of a questionnaire to assess health‐related quality of‐life (HRQOL) in people with epilepsy and the process of cross‐cultural translations of the questionnaire.

Methods: A sample of 304 adults with epilepsy from 25 seizure clinics in the United States was used to derive an abbreviated questionnaire focusing on epilepsy‐related issues from a longer, 89‐item instrument (QOLIE‐89). A rigorous forward‐backward‐forward system was used for cross‐cultural translation.

Results: A 31‐item questionnaire (QOLIE‐31, version 1.0) resulted, comprising seven subscales covering genral and epilepsy‐specific domains. Subscale and total scores can be calculated. The subscales were grouped into two factors: Emotional/Psychological Effects (seizure worry, overall QOL, emotional well‐being, energy/fatigue subscales) and Medical/Social Effects (medication effects, work‐driving‐social limits, cognitive function subscales). Cross‐cultural translations were made from U.S.‐English into Danish, Dutch, German, Canadian French, French, Italian, Spanish, Swedish, and U.K. English Versions 1.1.

Conclusions: Our results support the reliability and validity of the QOLIE‐31 (U.S.‐English version 1.0) as a measure of HRQOLIE. Cross‐cultural translations into nine other languages make it feasible to use the QOLIE‐31 (version 1.1) in multinational clinical trials after validation in each population or concurrent with clinical trial.
Vagus Nerve Stimulation for Symptomatic Generalized Epilepsy: A Pilot Study
Authors: Labar Douglas , Nikolov Blagovest , Tarver Brent , Fraser Richard
Published: August 2005

Summary: Purpose: Patients with symptomatic generalized epilepsy (SGE) may have antiepileptic drug (AED)‐resistant mixed generalized seizures. Vagus nerve stimulation (VNS) reduces partial seizures and may help SGE.

Methods: We added VNS to stable AED therapy in five SGE patients. Nine‐month postoperative VNS treatment seizure rates were compared to a 1 ‐month preoperative baseline.

Results: All patients had mixed generalized seizures, EEG generalized slow spike‐and‐wave and behavioral abnormalities. Median number of previous AEDs taken was 6 (range 5–12). Median baseline seizure rate was 75honth (range 29–1 10). VNS produced a median seizure rate production of ‐41% (range ‐40%–85%). Adverse events reported in one patient each were: incisional infection, choking sensation and voice change; and coughing (noted by two patients). One patient discontinued VNS due to coughing.

Conclusions: We conclude that VNS may be useful add‐on therapy for SGE. A larger, controlled, and blinded trial may be warranted.
Epilepsy, Vagal Nerve Stimulation by the NCP System, Mortality, and Sudden, Unexpected, Unexplained Death
Authors: Annegers J. F. , Coan Sharon P. , Hauser W.A. , Leestma J. , Duffell William , Tarver Brent
Published: August 2005

Summary: Purpose: To determine rates of all‐cause mortality and of sudden, unexpected, unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to contrast the NCP experience with other epilepsy cohorts.

Methods: A cohort of 791 individuals were followed for 1, 335 person‐years from implantation. Of the total cohort, 120 individuals had their NCP System devices deactivated. The 15 deaths which occurred during NCP System activation were reviewed for SUDEP by a panel. There were three additional deaths and 242.5 person‐years of monitoring after deactivation.

Results: The standardized mortality ratios for NCP System were 5.3, 95% confidence interval (CI) 3.0–8.7; and for the time period after device deactivation, 4.4, 95% CI 0.9–12.8. Six of the deaths during stimulation were considered definite or probable SUDEP and two as possible SUDEP. Seven were not considered to be SUDEP. The incidence of definite/probable SUDEP was 4.5 per 1,000 person‐years and 6.0 per 1,000 person‐years for definite/probable/possible SUDEP.

Conclusions: The mortality rates and standardized mortality ratios are comparable with studies of young adults with intractable epilepsy who were not treated with NCP System. These SUDEP rates are not significantly different from those reported in the recent studies of lamotrigine (LTG), gabapentin (GBP), and tiagabine (TGB). The higher rates of SUDEP in the NCP System cohort, as compared with recent drug trials, presumably is explained by the selection of relatively higher‐risk patients for the NCP System device.
Comparison of Effects of Valproate and Trans‐2‐en‐Valproate on Different Forms of Epileptiform Activity in Rat Hippocampal and Temporal Cortex Slices
Authors: Sokolova S. , Schmitz D. , Zhang C. L. , Löscher W. , Heinemann U.
Published: August 2005

Summary: Purpose: Reducing the extracellular magnesium or calcium or increasing the extracellular potassium induces different patterns of epileptiform activity in the hippocampus and the entorhinal cortex. Although in the low Ca2+ and K+ models, seizure‐like events (SLEs) develop in area CA1 of the hippocampus, only short recurrent discharges develop in the low Mg2+ model. In contrast, in low Mg2+, SLEs and late recurrent discharges (LRDs) are observed in the entorhinal cortex.

Methods: We compared the effects of valproate (VPA) and its major metabolite, trans‐2‐en‐VPA (TVPA), on all these different model activities using extracellular field potential measurements. We also investigated the equilibration time course of VPA in the slice by using VPA‐sensitive microelectrodes.

Results: Both drugs reversibly blocked most forms of epileptiform activity. The only exception was the LRDs in the entorhinal cortex. In paired experiments, TVPA appeared to be more effective than VPA bath applied with the same concentration to the same slice. With our measurements of the VPA concentrations in slices, we showed that the concentrations used were close to therapeutic drug levels.

Conclusions: If TVPA stands the toxicological tests, it might be a useful alternative in the treatment of seizures.
Clinical Usefulness of the Dipole Tracing Method for Localizing Interictal Spikes in Partial Epilepsy
Authors: Shindo Katsuro , Ikeda Akio , Musha Toshimitsu , Terada Kiyohito , Fukuyama Hidenao , Taki Waro , Kimura Jun , Shibasaki Hiroshi
Published: August 2005

Summary: Purpose: To clarify the clinical usefulness of the dipole tracing method in evaluation of interictal EEG spikes in patients with partial epilepsy.

Methods: Eight patients with partial epilepsy were studied. We compared the generator source of interictal spikes detected by the dipole tracing method with the results of magnetic resonance imaging (MRI), interictayictal measurement of cerebral blood flow (CBF) by single photon emission computed tomography (SPECT), interictal measurement of glucose metabolism by positron emission tomography (PET) and invasive electrocorticogram (ECoG).

Results: In 5 patients with mesial temporal lobe epilepsy (TLE), including 3 patients who underwent standard temporal lobectomy, the dipole tracing method showed results consistent with those of other examinations and better correlation with ECoG than with other noninvasive examinations. In a patient with mesial TLE who had defects in the skull due to previous surgery, the dipoles were located more laterally than expected. In a patient with frontal lobe epilepsy (FLE) who was finally proved to have an epileptogenic area in the lateral frontal area, the spike dipoles were identified in the medial side of the frontal lobe.

Conclusions: The dipole tracing method used in the present study is useful for localizing epileptogenic areas in patients with mesial TLE. However, in patients with partial skull defects and in those with FLE, the reliability of this method is still in accuracy of the lobe level.
Characterization and Comparison of Local Onset and Remote Propagated Electrographic Seizures Recorded with Intracranial Electrodes
Authors: Schiller Yitzhak , Cascino Gregory D. , Busacker Neil E. , Sharbrough Frank W.
Published: August 2005

Summary: Purpose: To compared the ictal discharge patterns between local onset and remote propagated electrographic seizures recorded with chronic intracranial electrodes.

Methods: The electrophysiological data from 88 consecutive patients who underwent chronic intracranial EEG monitoring were retrospectively reviewed. The early and late discharge patterns of electrographic seizures at local onset and distant propagated sites were determined by blinded visual inspection and computerized analysis.

Results: Four early and three late electrographic seizure patterns were observed at the local onset sites. The four early patterns consisted of a rhythmic discharge in the beta range (“beta buzz”), rhythmic alpha‐theta activity, rhythmic sharp waves in the delta range, and an irregular spike discharge. The three distinct late‐discharge patterns consisted of a late beta buzz, rhythmic sharp theta activity, and a rhythmic polyspike and wave discharge. At remote propagated sites, electrographic seizures could be divided into two different types according to their early discharge pattern. The first was unique to remote propagated electrographic seizures and consisted of a rhythmic theta‐delta activity correlated with the concurrent activity at the local‐onset site. The second remote initiation type consisted of patterns indistinguishable from the earlier discharge patterns recorded at the local onset site.

Conclusions: The initial ictal discharge pattern recorded with intracranial electrodes can assist in differentiating local onset and remote propagated electrographic seizures, with rhythmic round theta‐delta activity being unique to distant propagated sites. Nevertheless, the initial discharge of a subclass of remote propagated electrographic seizures consists of an independent pattern indistinguishable from that observed at local onset sites.
A Single‐Blind, Crossover Comparison of the Pharmacokinetics and Cognitive Effects of a New Diazepam Rectal Gel with Intravenous Diazepam
Authors: Cloyd James C. , Lalonde Richard L. , Beniak Thomas E. , Novack Gary D.
Published: August 2005

Summary: Purpose: The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat®) with intravenously administered DZP.

Methods: Twenty healthy volunteers were enrolled in a single‐blind, randomized, double‐dummy, two‐period, crossover study. Subjects received either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood samples for DZP and desmethyldiazepam analysis were obtained before the dose and from 3 min to 240 h after the dose. Heart rate and blood pressure were measured over the first 24‐h period. Subjects also completed five repetitions of a neuropsychological test battery over the first 8‐h period.

Results: Diazepam rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second maximum of 447 ± 91.1 ng/ml at ∼70 min. The absolute bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP were less alert and performed less efficiently on the WAIS Digit Symbol test 6 min after the dose. Subjects receiving DZP rectal gel performed less well on the WAIS Digit Span test 1 h after the dose and required more time to complete the Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug administration.

Conclusions: Diastat® displayed rapid, consistent absorption and was well tolerated. Alterations in cognition were mild and dissipated within 4 h of drug administration. This new rectal drug‐delivery system offers an easy, safe, and bioavailable method to administer DZP.
Seizure Patterns of Mongolian Gerbils Subjected to a Prolonged Weekly Test Schedule: Evidence for a Kindling‐Like Phenomenon in the Adult Population
Authors: Scotti A. L. , Bollag O. , Nitsch C.
Published: August 2005

Summary: Purpose: Mongolian gerbils (Meriones unguiculatus) seize in response to sensory stimulation and forced exploratory behavior, but the incidence and severity of their seizures are variable. We wished to characterize the seizure pattern of gerbils from our breeding colony.

Methods: Ninety‐three gerbils aged 1–16 months were tested for a mean of 24 consecutive weeks and assigned to a category according to their seizure pattern. Frequency distribution histograms of the mean scores assigned every 5 weeks were plotted for each category. Mean age, number of seizures, onset of the first facial and forelimb myoclonus, and of the first generalized tonic‐clonic seizure (GTCS) were compared among categories. We performed correlation analysis between onset of seizures and animal age.

Results: From the 93 tested, no seizure‐resistant gerbils could be isolated. Four major categories were distinguished. Category 1, highly seizure‐sensitive gerbils (39%), exhibited seizures from the first few weeks of test on. Category 2, consisting of ‐37%, were seizure‐free for the first three to six consecutive tests, later developing facial and forelimb myoclonus and eventually GTCS. Because such progressive development of seizures was similar to that occurring upon electrical kindling, the gerbils were classified as kindled‐like (KL). Among KL gerbils, older individuals were significantly more refractory to seizures. In category 3, gerbils (10%) exhibited inconsistent seizure behavior. Category 4 consisted of significantly younger animals (11%) with rapid progress to generalized seizures.

Conclusions: Seizures of progressive severity can be induced in adult gerbils with a prolonged test regimen. As a consequence, the number of regularly seizing gerbils in a colony can be increased. Prolonged tests starting at a defined age may help characterize seizure development better in this genetic model of limbic epilepsy.
Ictal Scalp EEG in Unilateral Mesial Temporal Lobe Epilepsy
Authors: Pataraia Ekaterina , Lurger Stefanie , Serles Wolfgang , Lindinger Gerald , Aull Susanne , Leutmezer Fritz , Bacher Johanna , Olbrich Achim , Czech Thomas , Novak Klaus , Deecke Lüder , Baumgartner Christoph
Published: August 2005

Summary: Purpose: We wished to determine the predictive significance of unilateral hippocampal atrophy and interictal spikes on localization of ictal scalp EEG changes and assess whether ictal EEG provides information that might change treatment or influence prognosis in patients with such characteristics of epilepsy.

Methods: We analyzed EEG seizure patterns in 118 seizures in 24 patients with unilateral mesial temporal lobe epilepsy (MTLE) defined by typical clinical seizure semiology, unilateral hippocampal atrophy on magnetic resonance imaging (MRI) and unitemporal spikes on interictal EEG. Two blinded electroencephalographers independently determined morphology, location, and time course of ictal EEG changes.

Results: Lateralization was possible in 88.4–92.0% of seizures and always corresponded to the side of the interictal spike focus and of hippocampal atrophy on MRI. Although only 30.4–33.9% of seizures were lateralized at onset, a later significant pattern emerged (12.6–13.3 s after EEG seizure onset) that allowed lateralization in 82.4–91.O% of seizures with non‐lateralized onset. Interobserver reliability for lateralization was excellent, with a K‐value of 0.85. In most patients, either all (79.2–83.3%) or >50% (8.3–16.7%) of seizures were lateralized. In only a small proportion of patients (4.2–8.3%) were 40% of seizures lateralized. In 1 patient, no seizure could be lateralized by 1 electroencephalographer. The results of ictal EEG recordings did not alter the surgical approach and did not correlate with surgical outcome.

Conclusions: We conclude that unilateral hippocampal atrophy on MRI and unitemporal interictal spikes can predict localization of ictal scalp EEG changes with a high degree of reliability and that ictal EEG provides no additional localizing information in this particular patient group.
Brain Blood Flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: I. Acute Effects at High and Low Levels of Stimulation
Authors: Henry Thomas R. , Bakay Roy A. E. , Votaw John R. , Pennell Page B. , Epstein Charles M. , Faber Tracy L. , Grafton Scott T , Hoffman John M.
Published: August 2005

Summary: Purpose: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei.

Methods: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < O.05, corrected for repeated measures).

Results: In both the low‐ and high‐stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal‐central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortexes, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high‐stimulation group had greater volumes of activation and deactivation sites.

Conclusions: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left‐sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.
Newly Diagnosed Epilepsy in Children: Presentation at Diagnosis
Authors: Berg Anne T. , Shinnar Shlomo , Levy Susan R. , Testa Francine M.
Published: August 2005

Summary: Purpose: The current understanding of epilepsy has changed significantly in the past 2 decades. This report presents a description of newly diagnosed childhood‐onset epilepsy, with a special emphasis on epilepsy syndromes, in a large, prospectively ascertained community‐based cohort evaluated and diagnosed in the mid‐1990s.

Methods: Children, aged 0 through 15 years at the time of the first seizure, were prospectively identified at the time of diagnosis of epilepsy through the practices of 16 of the 17 child neurologists in Connecticut as well as five adult neurologists and seven pediatricians from January 1993 through December 1997. Parents were interviewed, and all relevant medical records were reviewed. Classification of seizures and of epilepsy syndromes was done for each child by each of three pediatric neurologists, Discrepancies were resolved in conference.

Results: A total of 613 children was recruited into the study. The median age at time of the first seizure was 5.3 years. Half the cohort was boys. Eighteen percent had a remote symptomatic etiology. Epilepsy syndromes were classifiable in all but four children, although some syndromes are, by definition, relatively nonspecific. In this childhood‐onset cohort, 58.6% of the syndromes were localization related, 29.0% generalized, and 12.4% undetermined as to whether focal or generalized. Benign rolandic epilepsy occurred in 10% of the cohort. Primarily generalized syndromes accounted for 20.6%, with childhood absence being the single most common syndrome in this subgroup (12.1% of the cohort). Secondarily generalized syndromes accounted for 8.5% of the total, with infantile spasms being the most common in this grouping (3.9% of the cohort).

Conclusions: This study presents a description of childhood‐and adolescent‐onset epilepsy as it is diagnosed and evaluated in the 1990s in one state in the United State and based on current classification guidelines. The results should be generalizable to the rest of the country. The prognostic value of early identification of epilepsy syndromes will be determined through subsequent follow‐up of this cohort.
Valproate‐Induced Biochemical Abnormalities in Pregnancy Corrected by Vitamins: A Case Report
Authors: Baggot Paddy Jim , Kalamarides Jeremy A. , Shoemaker James D.
Published: August 2005

Summary: Purpose: Valproate (VPA) is a teratogenic anticonvulsant (AED), but vitamin supplementation has been suggested to limit the effect of VPA on the fetus. Maternal urinary metabolites were monitored to assess the metabolic effects of VPA before and after vitamin supplementation.

Methods: A pregnant woman with epilepsy receiving VPA and ethosuximide (ESM) was given high‐dose multivitamins from 13 to 28 weeks' gestation. Maternal urinary metabolites were measured throughout the pregnancy by gas chromatography/mass spectrometry.

Results: Before multivitamin supplementation began, the patient had significantly increased excretion rates of α‐ketoglutarate, β‐lactate, pyruvate, lactate, methylmalonate, and other metabolites compared with normal pregnant women. During multivitamin supplementation, many previously increased excretion rates decreased significantly. Fetal head growth was normal up to 30 weeks, but then lagged. Bitemporal narrowing was noted at birth.

Conclusions: VPA may cause metabolic abnormalities in pregnancy. Many biochemical abnormalities attributable to VPA in this patient were corrected with high‐dose multivitamin supplementation. The specific relation between biochemical abnormalities and VPA teratogenesis remains to be determined.
Unidirectional Olfactory Hallucination Associated with Ipsilateral Unruptured Intracranial Aneurysm
Authors: Mizobuchi Masahiro , Ito Naoki , Tanaka Chiharu , Sako Kazuya , Sumi Yoshihiro , Sasaki Takehiko
Published: August 2005

Summary: Purpose: We describe a patient with complex partial seizure with unidirectional olfactory aura associated with ipsilateral unruptured aneurysm.

Methods and Results: The patient felt a sweet pleasant smell coming from behind her right side every time before the attack. Cranial magnetic resonance imaging (MRI) and three‐dimensional computed tomography (CT) angiography revealed a large aneurysm at the bifurcation of the right middle cerebral artery and compression of the right orbitofrontal cortex. Small spikes were recorded from the right orbitofrontal and superior temporal gyri and from the uncus by the cortical electrodes during clipping of the aneurysm.

Conclusions: The orbitofrontal cortex may have a function related to the ipsilateral directional olfactory sensation.
FOS Induction in Brain Associated with Seizure and Sustained Cortical Vasodilation in Anesthetized Rat
Authors: Mraovitch Sima , Calando Yolande
Published: August 2005

Summary: Purpose: By estimating the anatomical distribution of neurons expressing c‐fos protein, we sought to establish whether the intrinsic neurol systems known to be implicated in the cerebrovascular regulation were activated during the increase in cortical blood flow associated with epileptic seizures.

Methods: A single unilateral microinjection of the cholinergic agonist, carbachol, in the thalamic generalized convulsive seizure area was used in anesthetized rats to elicit recurrent episodes of electrocortical epileptiform activity and an increase in cortical blood flow. Neuronal expression of Fos protein was analyzed to identify activated brain regions.

Results: We identified two cortical vasodilatory responses: a sustained cortical vasodilatory response associated with the continuous low‐frequency, high‐amplitude spiking and a transient cortical vasodilatory response invariably related to the recurrent spike‐burst activity. The sustained cortical blood flow began to increase at 55–65 min, remaining significantly (p < 0.05) increased and reaching at the end of the experiment ≤182 ≤17% of the prestimulated control. The electrocortical epileptic activity and the cerebral cortical vasodilation were associated with a marked increase in Fos immunoreactivity in the entorhinal and piriform cortices, the dentate gyrus, the hippocampus, and the amygdala. Fos‐positive neurons also were found in specific thalamic nuclei, the cerebral cortex, the caudate‐putamen, the hypothalamus, the pontine parabrachial nuclei, the dorsal raphe, and the rostral ventrolateral medulla.

Conclusions: These results provide evidence that convulsive seizures elicited by cholinergic stimulation of the thalamus, in addition to limbic and somatic motor systems, activate central autonomic nuclei and their pathways, including those implicated in cerebrovascular regulation.
The Descriptive Epidemiology of Infantile Spasms Among Atlanta Children
Authors: Trevathan Edwin , Murphy Catherine C. , Yeargin‐Allsopp Marshalyn
Published: August 2005

Summary: Purpose: To determine the population‐based epidemiology of infantile spasms (IS) among Atlanta children.

Methods: By using data from a cross‐sectional, population‐based surveillance system that included 21 EEG laboratories, we identified children born in 1975–1977 in metropolitan Atlanta with IS. Cumulative incidence up to age 2 years was estimated from the number of children with IS born in the study area in 1975–1977, and age‐specific prevalence was calculated from the number of children previously diagnosed with IS who lived in the study area at age 10 years. Data regarding coexisting disabilities were available from the surveillance system for developmental disabilities.

Results: The cumulative incidence of IS was 2.9/10,000 live births; half of the children with IS had cryptogenic IS. The age‐specific prevalence of IS was 2.0/10,000 among 10‐year‐old children. Eighty‐three percent of 10‐year‐old children with a history of IS had mental retardation (MR, IQ ≤70); 56% of children with a history of IS had profound MR (IQ <20). Developmental outcome did not differ between the children with cryptogenic IS and those with symptomatic IS. Among the 10‐year‐old children with profound MR who were living in Atlanta at age 10 years, 12% had a history of IS. Fifty percent of children with IS developed Lennox‐Gastaut syndrome (LGS) before age 11 years.

Conclusions: The syndrome of IS is rare in the general population, yet a significant percentage of all children with profound MR and severe childhood epilepsy syndromes in the general population have a history of IS.