bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Quantitative T2 Relaxometry and Memory in Nonlesional Temporal Lobe Epilepsy
Authors: Wendel J. D. , Trenerry M. R. , Xu Y. C. , Sencakova D. , Cascino G. D. , Britton J. W. , Lagerlund T. D. , Shin C. , So E. L. , Sharbrough F. W. , Jack C. R.
Published: March 2003

Summary:  Purpose: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre‐ and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy.

Methods: Pre‐ and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale–Revised (WMS–R) and the 30‐min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients.

Results: In left temporal lobe–onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right‐minus‐left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe–onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal–onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance.

Conclusions: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI‐determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.
Development and Validation of the Glasgow Epilepsy Outcome Scale (GEOS): A New Instrument for Measuring Concerns about Epilepsy in People with Mental Retardation
Authors: Espie Colin A. , Watkins Jessamy , Duncan Roderick , Espie Audrey , Sterrick Mark , Brodie Martin J. , McGarvey Christine , Curtice Lisa
Published: March 2003

Summary:  Purpose: To develop a measure for use with adults with epilepsy and mental retardation, capable of assessing both clinical and care concerns and of quantifying treatment outcomes.

Methods: Extensive validational and other psychometric evaluation was undertaken, comprising initial scale development work with 48 carers and 46 health practitioners, followed by formal field testing on a sample of 186 patients, using 384 respondents (160 clinicians, 141 staff, 83 family). Recognised qualitative methods were applied to identify central themes, and psychometric procedures generated data on validity, reliability, and component structure.

Results: A total of 1,007 items of concern was generated, which was reduced systematically to a representative set of 90 items. The GEOS‐90 comprises four subscales: concerns about “seizures,”“treatment,”“caring,” and “social impact,” each explaining ∼70% of variance. Subscales and factor scales had strong internal consistency (α≥ 0.82). Stepwise linear regression was applied to derive a short‐form version with similar structure. Thirty‐five items were retained (GEOS‐35; α≥ 0.89). Both scales discriminated moderately on clinical variables (number of seizure types, mono‐ vs. polytherapy, seizure frequency; all values of p < 0.05) and demonstrated concurrent validity with interview ratings from the ELDQOL (p < 0.05).

Conclusions: The GEOS scales appear valid and reliable for use with clinical populations of people with mental retardation.
Epilepsy in the Elderly: Some Clinical and Pharmacotherapeutic Aspects
Authors: Krämer Günter
Published: March 2003

Summary: The majority of epileptic seizures and epilepsies are no longer manifested in childhood and adolescence; instead their incidence is higher at the age of 65 years or older than during the first two decades of life. After cerebrovascular disorders and dementias, epileptic seizures and epilepsies now constitute the third most frequent neurologic problem encountered in the elderly. Important clinical features of epilepsy in the elderly related to the diagnosis include the most common seizure types and causes. Special features of drug treatment for epilepsy in the elderly result not only from the physiologic changes in the elderly but also from the particular pharmacology of the respective drugs. Because elderly patients very often require other long‐term medication in addition to antiepileptic therapy, drug interactions between different antiepileptic drugs and between antiepileptics and other drugs can be of major significance. Other special features of pharmacotherapy for epilepsy in the elderly include the presence of liver and kidney diseases.
Topiramate and Metabolic Acidosis in Pediatric Epilepsy
Authors: Takeoka Masanori , Holmes Gregory L. , Thiele Elizabeth , Bourgeois Blaise F. , Helmers Sandra L. , Duffy Frank H. , Riviello James J.
Published: March 2003

Summary:  Purpose: Topiramate (TPM) has been widely used as an adjunctive therapy for treating epilepsy. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3‐).

Methods: Clinical data from 30 children who received TPM as adjunctive therapy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3‐levels were assessed before, during, and after discontinuing TPM (n = 9). When multiple data were available, mean values were used for analysis.

Results: Of the 30 patients, 21 had a >10% decrease in HCO3‐ levels. The mean decrease in HCO3‐ among the 21 patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred, and HCO3‐ supplement was not needed, except for one patient who developed tachypnea from worsened acidosis after prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of efficacy, and in two because of anorexia. After discontinuing TPM, the serum HCO3‐ returned to the previous level before starting TPM in all nine.

Conclusions: Decreased HCO3‐ levels occurred in the majority of patients reviewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3‐ may cause significant consequences, such as severe acidosis or renal calculi. Monitoring HCO3‐ levels before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.
Antiepileptic Drug Withdrawal in Patients with Temporal Lobe Epilepsy Undergoing Presurgical Video‐EEG Monitoring
Authors: Yen Der‐Jen , Chen Chien , Shih Yang‐Hsin , Guo Yuh‐Cherng , Liu Li‐Ting , Yu Hsiang‐Yu , Kwan Shang‐Yeong , Yiu Chun‐Hing
Published: March 2003

Summary:  Purpose: To investigate antiepileptic drug (AED) withdrawal during video‐EEG monitoring in adult patients with temporal lobe epilepsy (TLE).

Methods: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4–6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS).

Results: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16–451 h) was required for completing the monitoring in each patient. Forty‐three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal.

Conclusions: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video‐EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.
Genetic Predisposition to Severe Myoclonic Epilepsy in Infancy
Authors: Benlounis A. , Nabbout R. , Feingold J. , Parmeggiani A. , Guerrini R. , Kaminska A. , Dulac O.
Published: March 2003

Summary:  Purpose: To address genetic predisposition to febrile convulsions (FCs) and epilepsy as an etiologic background of severe myoclonic epilepsy in infancy (SMEI).

Methods: Familial antecedents of epilepsy and FCs were analyzed in four groups of patients with SMEI (65 cases), FCs (57 cases), childhood absences (67 cases), and a control group of patients with no neurologic problems (64 cases).

Results: Patients with SMEI and those with FCs had significantly increased incidence of FCs in their relatives compared with those with absence epilepsy and with the control group. The incidence of epilepsy in relatives of patients with SMEI and absence epilepsy was increased compared with that in the control group and reached statistical significance. Epilepsy in relatives with SMEI had the characteristics of idiopathic generalized epilepsy.

Conclusions: A genetic predisposition could determine three types of epileptic syndromes: FCs, idiopathic generalized epilepsy, and SMEI.
On the Association Between Valproate and Polycystic Ovary Syndrome
Authors: Genton Pierre , Bauer Jürgen , Duncan Susan , Taylor Ann E. , Balen Adam H. , Eberle Andrea , Pedersen Birthe , Salas‐Puig Xavier , Sauer Mark V.
Published: March 2003

Summary: Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility, hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.
Newly Diagnosed Unprovoked Epileptic Seizures: Presentation at Diagnosis in CAROLE Study
Authors: Jallon Pierre , Loiseau Pierre , Loiseau Jérome ,   on behalf of Groupe CAROLE (Coordination Active du Réseau Observatoire Longitudinal de l'Epilepsie)
Published: March 2003

Summary:  Purpose: We describe first unprovoked seizures and newly diagnosed epilepsies at initial presentation, with a special emphasis on epilepsy syndromes, in a large cohort recruited in the mid‐1990s in France.

Methods: The French Foundation for Research on Epilepsy set up a network to conduct a prospective study of patients with newly diagnosed unprovoked seizures. Information was provided by 243 child or adult neurologists. Four neurologists classified each case according to the International League Against Epilepsy (ILAE) criteria. First‐seizure patients and patients with previously undiagnosed seizures were compared.

Results: Between May 1, 1995, and June 30, 1996, 1,942 patients aged from 1 month to 95 years were identified: 926 (47.7%) with a single seizure and 1,016 (52.3%) with newly diagnosed epilepsy. All but 17 patients had EEGs. In the first‐seizure and newly‐diagnosed‐epilepsy groups, neuroimaging studies were performed in 78.2 and 68.3% of patients, and medication prescribed in 54.1 and 89.6%, respectively. There were significant differences between the two groups with respect to age at onset and diagnosis, sex, etiology, several specific syndromes, as well as the type and presentation of initial seizure. In patients for whom the first seizure was convulsive, only sex, multiple seizures in a day or status epilepticus, and cryptogenic localization‐related syndrome differed between the two groups.

Conclusions: Approximately half of patients who first came to attention for an unprovoked seizure already met epidemiologic criteria for epilepsy. There were significant differences between the types of patients with a first seizure and those with newly diagnosed epilepsy. One or several seizures at diagnosis did not influence the diagnostic assessment of the patients but had a strong influence on the initiation of treatment.
The Effect of Lamotrigine on Epileptiform Discharges in Young Patients with Drug‐Resistant Epilepsy
Authors: Eriksson A‐S. , Knutsson E. , Nergårdh A.
Published: March 2003

Summary:  Purpose: In a double‐blind crossover study with lamotrigine (LTG), we investigated a possible relationship between the clinical responses and changes of the amount of epileptiform activity in EEG.

Methods: Twelve patients, aged 4–21 years, with generalized drug‐resistant epilepsy who had responded to LTG, completed the study. Twenty‐four‐hour video‐EEGs were taken during control, placebo, and drug phases. The amounts of epileptiform discharges were estimated and compared with the clinical effects.

Results: The duration of periods of repeated epileptiform discharges was significantly reduced during the LTG phase compared with the placebo phase (n = 12, p = 0.04). Ten patients showed a reduction of the amount of epileptiform discharges in the LTG phase by a mean of 81% (range, 17–100%). Periods of repeated epileptiform discharges with duration longer than 30 s were significantly reduced in length (p = 0.03) and number (p = 0.04) during the LTG phase compared with the placebo phase. Shorter periods of epileptiform discharges and the numbers of single epileptiform discharges were not affected. In five patients there was a seizure reduction (≥50%) concomitant with the reduction of epileptiform discharges in the EEG. The behavior improved during LTG treatment in all patients. The patients became more alert, and their concentration and performance improved, according to their parents and the medical personnel.

Conclusions: LTG in dosages of 1–8 mg/kg body weight was found to depress relatively long episodes of interictal, repetitive, epileptiform activity in young patients with drug‐resistant epilepsy, whereas short episodes were not affected. It depressed seizures in about half of the patients studied but gave improvements of behavior in all patients.
The Absence of Interictal Spikes with Documented Seizures Suggests Extratemporal Epilepsy
Authors: Stüve O. , Dodrill C. B. , Holmes M. D. , Miller J. W.
Published: March 2003

Summary:  Purpose: To determine the demographic and clinical characteristics of patients who have documented epileptic seizures on long‐term video‐EEG monitoring who do not have interictal spikes.

Methods: The records of 1,223 monitoring studies from 919 patients who underwent noninvasive long‐term video‐EEG monitoring were reviewed. In 28 patients (3.0% of monitored patients, 4.4% of patients with electrographic evidence of epilepsy), no interictal spikes were found despite the occurrence of at least one recorded electrographic seizure. The demographic, medical, neuropsychological, and EEG data of these patients were compared with those of 28 matched control patients with documented interictal spikes.

Results: Extratemporal seizures were significantly more frequent in the patients with at least one recorded epileptic seizure but without interictal spikes compared with patients with epileptic seizures and interictal spikes (p = 0.031). The only other significant difference between the groups (p = 0.016) was a later age at seizure onset (18.3 vs. 10.7 years) for the patients without interictal spikes. Age at evaluation, gender, handedness, clinical seizure type, family history of epilepsy, history of febrile seizures, neuropsychological testing, and neurologic and psychiatric history did not differ between the two groups.

Conclusions: In patients with documented epilepsy without interictal spikes on EEG monitoring, the possibility of an extratemporal focus should be considered.
Pharmacokinetic Study of Levetiracetam in Children
Authors: Pellock John M. , Glauser Tracy A. , Bebin E. Martina , Fountain Nathan B. , Ritter Frank J. , Coupez René M. , Shields W. Donald
Published: March 2003

Summary:  Purpose: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open‐label, single‐dose study.

Methods: Twenty‐four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24‐h pharmacokinetic evaluation.

Results: In children, the half‐lives of levetiracetam and its metabolite ucb L057 were 6.0 ± 1.1 and 8.1 ± 2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1‐mg/kg dose were lower in children (Cmax, norm = 1.33 ± 0.35 μg/ml; AUCnorm = 12.4 ± 3.5 μg/h/ml) than in adults (Cmax, norm = 1.38 ± 0.05 μg/ml; AUCnorm = 11.48 ± 0.63 μg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 ± 0.36 ml/min/kg) was ∼30–40% higher in children than in adults. Levetiracetam was generally well tolerated.

Conclusions: On the basis of these data, a daily maintenance dose equivalent to 130–140% of the usual daily adult maintenance dosage (1,000–3,000 mg/day) in two divided doses, on a weight‐normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.
Clinical Features and Prognosis of Nonepileptic Seizures in a Developing Country
Authors: Silva W. , Giagante B. , Saizar R. , D′Alessio L. , Oddo S. , Consalvo D. , Saidón P. , Kochen S.
Published: March 2003

Summary:  Purpose: To determine the predictive value of clinical features and medical history in patients with nonepileptic seizures (NESs).

Methods: One hundred sixty‐one consecutive ictal video‐EEGs were reviewed, and 17 patients with 41 NESs identified. NES diagnosis was defined as paroxysmal behavioral changes suggestive of epileptic seizures recorded during video‐EEG without any electrographic ictal activity. Clinical features, age, sex, coexisting epilepsy, associated psychiatric disorder, social and economic factors, delay in reaching the diagnosis of NES, previous treatment, and correlation with outcome on follow‐up were examined.

Results: The study population included 70% female patients with a mean age of 33 years. Mean duration of NESs before diagnosis was 9 years. Forty‐one percent had coexisting epilepsy. The most frequent NES clinical features were tonic–clonic mimicking movements and fear/anxiety/hyperventilation. The most common psychiatric diagnosis was conversion disorder and dependent and borderline personality disorder. Seventy‐three percent of patients with pure NESs received antiepileptic drugs (AEDs), and 63.5% of this group received new AEDs. Fifty‐nine percent of the patients received psychological/psychiatric therapy. At follow‐up, 23.5% were free of NESs.

Conclusions: All seizure‐free patients had two good prognostic factors: having an independent lifestyle and the acceptance of the nonepileptic nature of the episodes. Video‐EEG monitoring continues to be the diagnostic method to ensure accurate seizure classification. Establishing adequate health care programs to facilitate access to new technology in public hospitals as well as the implementation of continuous education programs for general practitioners and neurologists could eventually improve the diagnosis and treatment of patients with NESs.
Focal Cortical Dysplasias in Eloquent Cortex: Functional Characteristics and Correlation with MRI and Histopathologic Changes
Authors: Marusic Petr , Najm Imad M. , Ying Zhong , Prayson Richard , Rona Sabine , Nair Dileep , Hadar Eldad , Kotagal Prakash , Bej Mark D. , Wyllie Elaine , Bingaman William , Lüders Hans
Published: March 2003

Summary:  Purpose: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features.

Methods: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics.

Results: Language or motor areas were colocalized with epileptogenic regions (n = 6 of 8, 75%), but were not mapped in regions of increased signal on fluid‐attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n = 5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells.

Conclusions: We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.
Lack of Neuronal Damage in Atypical Absence Status Epilepticus
Authors: Shirasaka Yukiyoshi
Published: March 2003

Summary:  Purpose: Whether status epilepticus of nonconvulsive epileptic seizures is harmful still remains controversial. To investigate this, the presence and/or extent of neuronal damage in patients with absence status epilepticus (ASE) and patients with complex partial status epilepticus (CPSE) was examined and compared.

Methods: Neuron‐specific enolase (NSE) in CSF was examined in the patients with ASE and compared with that of the patients having CPSE. Clinical aspects of these patients also were investigated.

Results: CSF NSE levels in ASE patients were lower than those of CPSE patients and were considered as the normal values. No clinical symptoms indicated neuronal damage in the ASE patients.

Conclusions: This study suggests that ASE does not induce neuronal damage. Serum NSE is not always correlated to CSF NSE, and determination of serum NSE levels may be an inappropriate method of estimating neuronal damage in some cases of ASE.
An Association between Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis and Human Leukocyte Antigens
Authors: Özkara Çigdem , Altintas Ayse , Yilmaz Erkan , Eskazan Esat , Erkol Gökhan , Özyurt Emin , Erdogan Ergun , Kuday Cengiz
Published: March 2003

Summary:  Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is one of the medically intractable epilepsies that may be remediable with surgery. Although the pathogenesis of HS still remains obscure, genetics may play a role as a predisposing factor, with the genetically controlled immune system as one of its aspects. Our aim in this study was to investigate whether there is any association between human leukocyte antigens (HLAs) that are related to chromosome 6 and this specific type of epilepsy.

Methods: HLA class I and II typing were performed with the microlymphocytotoxicity method on 65 Turkish patients with MTLE‐HS and on 184 healthy controls.

Results: Our study revealed a significantly high frequency of class II antigens HLA‐DQ2, ‐DR4, and ‐DR7 alleles and the combination of HLA‐DR4‐DQ2, and DR7‐DQ2 alleles.

Conclusions: The HLA alleles that occur with increased frequency in many HLA‐ associated conditions appear to serve as risk factors that increase susceptibility but are not essential for disease expression. Our data support the role of genetic factors in the development of HS, possibly related to early childhood events that may act as a trigger factor to initiate the cascade in genetically prone patients with specific HLA types to give rise to MTLE eventually.
Is a Cortical Spike Discharge “Transferred” to the Contralateral Cortex via the Corpus Callosum?: An Intraoperative Observation of Electrocorticogram and Callosal Compound Action Potentials
Authors: Ono Tomonori , Matsuo Atsuko , Baba Hiroshi , Ono Kenji
Published: March 2003

Summary:  Purpose: By means of the intraoperative electrophysiologic observation, we reevaluated the “transfer” theory that a transcallosal volley invoked by a cortical spike discharge in one hemisphere directly causes its contralateral counterpart via the corpus callosum (CC).

Methods: Twenty‐six patients who underwent corpus callosotomy were the subjects of this study. Intraoperatively, electrocorticograms from both hemispheres were simultaneously monitored with callosal compound action potentials (CCAPs) from the CC. Analysis was conducted on (a) the interhemispheric delay of bilaterally synchronous spike‐and‐wave discharges (BSSWs), and (b) the chronological relation between BSSWs and CCAPs.

Results: The side of prior spike discharges was never fixed but was occasionally reversed. Interhemispheric delays between the BSSWs were not constant, regardless of direction, and fluctuated in all patients. Most of the interhemispheric delays were distributed within 20 ms with a mode of 0 ms. The waveform of the CCAP was characterized by slow‐rising negative potential change that attained its peak after a cortical spike discharge. These findings were identical in all the patients regardless of whether the BSSWs were changed or unchanged after callosotomy.

Conclusions: If the “transfer” role of the CC is true, interhemispheric delays between BSSWs must be longer than interhemispheric axonal conduction time (about 20 ms), and a preceding cortical spike discharge must produce a CCAP and then a contralateral one in order of time. However, this hypothesis was not confirmed in the present study. We propose the interhemispheric recruitment of the epileptogenic state as a different role of the CC on epileptogenesis.
Masking Synchronous GABA‐mediated Potentials Controls Limbic Seizures
Authors: Barbarosie Michaela , Louvel Jacques , D'Antuono Margherita , Kurcewicz Irène , Avoli Massimo
Published: March 2003

Summary:  Purpose: We determined how CA3‐driven interictal discharges block ictal activity generated in the entorhinal cortex during bath application of 4‐aminopyridine (4AP, 50 μM).

Methods: Field potential and [K+]o recordings were obtained from mouse combined hippocampus–entorhinal cortex slices maintained in vitro.

Results: 4AP induced N‐methyl‐d‐aspartate (NMDA) receptor–dependent ictal discharges that originated in the entorhinal cortex, disappeared over time, but were reestablished by cutting the Schaffer collateral (n = 20) or by depressing CA3 network excitability with local application of glutamatergic receptor antagonists (n = 5). In addition, two types of interictal activity occurred throughout the experiment. The first type was CA3 driven and was abolished by a non‐NMDA glutamatergic receptor antagonist. The second type was largely contributed by γ‐aminobutyric acid type A (GABAA) receptor–mediated conductances and persisted during blockade of glutamatergic transmission. The absence of CA3‐driven interictal discharges in the entorhinal cortex after Schaffer collateral cut facilitated the GABA‐mediated interictal potentials that corresponded to large [K+]o elevations and played a role in ictal discharge initiation. Accordingly, ictal discharges along with GABA‐mediated interictal potentials disappeared during GABAA‐receptor blockade (n = 7) or activation of μ‐opioid receptors that inhibit GABA release (n = 4).

Conclusions: Our findings suggest that CA3‐driven interictal events restrain ictal discharge generation in the entorhinal cortex by modulating the size of interictal GABA‐mediated potentials that lead to large [K+]o elevations capable of initiating ictal discharges in this structure.
Familial Temporal Lobe Epilepsy with Aphasic Seizures and Linkage to Chromosome 10q22‐q24
Authors: Brodtkorb Eylert , Gu Wenli , Nakken Karl O. , Fischer Christine , Steinlein Ortrud K.
Published: March 2003

Summary:  Purpose: To describe the phenotypic expression of a new family with familial lateral temporal lobe epilepsy with aphasic seizures, and to compare the findings with the clinical features of previously reported families linked to chromosome 10q22‐q24.

Methods: Medical records were collected from 12 living affected members. The patients underwent a personal interview and a clinical neurologic examination. Results from interictal scalp EEGs and neuroimaging examinations were obtained.

Results: The cardinal ictal symptom was a brief sensory aphasia in eight of the patients. In four, this was accompanied by auditory symptoms, usually in the form of monotonous unformed sounds. Simple partial seizures with psychic or somatosensory seizures also were present. Visual ictal symptoms and complex partial seizures were absent. All patients had generalized tonic–clonic seizures. Magnetic resonance imaging (MRI) or computed tomography (CT) did not reveal morphologic correlates. Improvement with age seemed to occur in many patients. Significant linkage to chromosome 10q22‐q24 was established by testing 17 polymorphic microsatellite markers.

Conclusions: The epilepsy of this family appears to represent a variety of autosomal dominant lateral temporal lobe epilepsy. Aphasic seizures and a peculiar seizure‐precipitating effect of the activation of speech (initiation or perception) may serve as markers for identifying further families with this phenotype.
Effect of Gabapentin on the Anticonvulsant Activity of Antiepileptic Drugs against Electroconvulsions in Mice: An Isobolographic Analysis
Authors: Borowicz Kinga K. , Swiader Mariusz , Luszczki Jarogniew , Czuczwar Stanislaw J.
Published: March 2003

Summary:  Purpose: The objective of this study was the isobolographic evaluation of the interactions between the novel antiepileptic drug (AED) gabapentin (GBP) and a number of other AEDs against electroconvulsion‐induced convulsions in mice.

Methods: Electroconvulsions were produced by means of an alternating current (ear‐clip electrodes, 0.2‐s stimulus duration, tonic hindlimb extension taken as the end point). Adverse effects were evaluated with the chimney test (motor performance) and passive‐avoidance task (long‐term memory). Plasma levels of AEDs were measured by immunofluorescence or high‐pressure liquid chromatography.

Results: GBP (≤50 mg/kg) remained ineffective on the electroconvulsive threshold. According to the isobolographic analysis, GBP appears to act synergistically with carbamazepine, valproate, phenytoin, phenobarbital (PB), lamotrigine (LTG), and LY 300164. The pharmacokinetic events may be responsible for the interactions of GBP/PB and GBP/LTG, because only PB and LTG significantly elevated the plasma concentration of this AED. Conversely, GBP did not affect the plasma levels of other AEDs used in this study. No adverse effects were induced by combinations of GBP with these AEDs.

Conclusions: The isobolographic analysis revealed that combinations of GBP with other AEDs generally results in synergistic (supraadditive) interactions.
Hyperventilation‐induced High‐amplitude Rhythmic Slowing with Altered Awareness: A Video‐EEG Comparison with Absence Seizures
Authors: Lum Leanna M. , Connolly Mary B. , Farrell Kevin , Wong Peter K. H.
Published: March 2003

Summary:  Purpose: Hyperventilation‐induced high‐amplitude rhythmic slowing (HIHARS) in children may be associated with clinical episodes of altered awareness. The presence of automatisms has been proposed as a distinguishing feature that helps to differentiate absence seizures from nonepileptic causes of decreased responsiveness. This retrospective, controlled, video‐EEG study compared the clinical characteristics of episodes of HIHARS with loss of awareness with those of absence seizures.

Methods: The database of a tertiary Children's Hospital was searched for patients studied between April 1993 and April 1997 who had at least one episode of HIHARS with loss of awareness. The absence control group was obtained by selecting the next patient, after an HIHARS study subject, who met the following criteria: (a) had at least one absence seizure occurred during hyperventilation in the EEG recording, and (b) had a diagnosis of idiopathic generalized epilepsy. The video‐EEG and medical histories of all patients were reviewed and summarized.

Results: We reviewed video‐EEG recordings of 77 episodes of HIHARS with loss of awareness from 22 children and 107 absence seizures during hyperventilation from 22 children. Eye opening and eyelid flutter were seen more frequently in absence seizures, whereas fidgeting, smiling, and yawning occurred more frequently during HIHARS episodes. Arrest of activity, staring, and oral and manual automatisms were observed in both groups.

Conclusions: Automatisms are common in both HIHARS and absence seizures. Yawning, smiling, and particularly fidgeting occur more commonly and eye opening and eyelid flutter less commonly in HIHARS. However, episodes of HIHARS with loss of awareness clinically mimic absence seizures, and these conditions can be distinguished reliably only by EEG.
Effects of Educational Intervention on Changing Parental Practices for Recurrent Febrile Convulsions in Taiwan
Authors: Huang Mei‐Chih , Liu Ching‐Chuan , Chi Yun‐Chan , Thomas Karen , Huang Chao‐Ching
Published: March 2003

Summary:  Purpose: To evaluate the effects of educational interventions on parental practices for recurrent febrile convulsions (FC).

Methods: A 2‐year follow‐up, nonequivalent comparison group design was used to evaluate the intervention effects. Two educational interventions were provided for FC parents in southern Taiwan. The 326 parents voluntarily chose either to receive a mailed pamphlet (n = 196) or to attend a 2‐h educational program (n = 130). Five telephone interviews focused on investigating FC episodes and parental practices for seizures were conducted at months 3, 6, 12, 18, and 24 after the interventions.

Results: Of the 326 FC children, 78 (23.9%) had recurrent FCs within the 2‐year follow‐up. Parents who only received pamphlets did not show significant improvements. Parents who attended the educational program demonstrated significant improvements in the recommended practices, particularly in protecting the convulsing child (8.3 vs. 36.1%; p = 0.02 by McNemar) and placing the child on his or her side (19.4 vs. 47.2%; p = 0.01). Nonrecommended practices including rushing the convulsing child to the hospital (88.9 vs. 30.6%; p < 0.01) and putting protective devices in the child's mouth (38.9 vs. 8.3%; p < 0.01) significantly decreased. By generalized estimating equation analyses, the types of interventions are the single significant factor influencing parental practice changes from initial to recurrent FCs.

Conclusions: Most parents used inappropriate practices for their child's initial FC. Compared with the mailed pamphlet, the educational program had significant improvements in recommended and nonrecommended practices from initial to recurrent FCs.
Is Refractory Epilepsy Preventable?
Authors: Arroyo Santiago , Brodie Martin J. , Avanzini Giuliano , Baumgartner Christoph , Chiron Catherine , Dulac Olivier , French Jacqueline A. , Serratosa José M.
Published: March 2003

Summary: About a third of the patients diagnosed with epilepsy will not be fully controlled with antiepileptic drugs (AEDs), and many of them will have frequent and disabling seizures. These patients will undergo multiple drug trials, most often without complete seizure remission. Moreover, refractory epilepsy is associated with increased morbidity (from seizures and medications), social isolation, unemployment, and overall reduced quality of life. There is evidence that refractory epilepsy can be a progressive disorder, which, if controlled early, might never develop into a full syndrome with all of its associated sequelae. The difficulty lies in identifying at an early stage patients who are likely to progress to intractability. No currently known markers enable clinicians to make this identification with confidence. Advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy may change this situation. Even now, we are able to identify many patients with a poor prognosis earlier than before, particularly in the pediatric population, in which syndromic classification may provide an approach to predict intractability. The early initiation of aggressive therapy may improve outcome and overall quality of life.
The Effect of Age on Seizure Semiology in Childhood Temporal Lobe Epilepsy
Authors: Fogarasi András , Jokeit Hennric , Faveret Eduardo , Janszky József , Tuxhorn Ingrid
Published: March 2003

Summary:  Purpose: Complex partial seizure is the characteristic seizure type observed in epilepsy arising from temporal lobe structures. The seizure evolution in adult patients is quite stereotyped and well characterized, manifesting initially with an aura, behavioral arrest, and oroalimentary and gestural automatism. A greater variability of semiology including motor features with tonic or myoclonic components, as well as a paucity of automatism, has been reported in young children with temporal lobe epilepsy. The aim of our study was to examine in more detail the effects of age on individual ictal features to be able to determine the critical age when lesional temporal lobe seizure semiology undergoes transition from the pediatric to the more adult‐type clinical pattern.

Methods: We performed a video analysis of 83 seizures from 15 children (aged 11–70 months) selected by post–temporal lobectomy seizure‐free outcome, looking specifically at the motor and behavioral (nonmotor) manifestations in relation to age of the children.

Results: All of the children younger than 42 months had seizures with early and marked motor features, which included tonic and myoclonic components and epileptic spasms. Parallel with age, the frequency of these motor components decreased, and in five of 11 children older than 3 years, motor features were totally absent. Analyzed quantitatively, we saw a linear and inverse correlation of the ratio of motor components with age at monitoring.

Conclusions: These findings support the hypothesis that events in brain maturation significantly affect clinical seizure semiology and may override the more typical localizing features seen in adult‐type temporal lobe epilepsy. These findings are important to consider in the early diagnosis of childhood temporal lobe epilepsy.
Interictal EEG Abnormalities in Patients with Psychogenic Nonepileptic Seizures
Authors: Reuber Markus , Fernández Guillen , Bauer Juergen , Singh Daman D. , Elger Christian E.
Published: March 2003

Summary:  Purpose: To examine interictal EEG abnormalities in patients with psychogenic nonepileptic seizures (PNESs).

Methods: (a) Retrospective study of EEG reports of 187 consecutive patients with PNES seen at the Department of Epileptology, Bonn, Germany; (b) Blinded, multirater comparison of EEGs of all PNES patients with no other clinically recognizable cause of EEG disturbance (n = 50) and healthy controls (n = 50).

Results: Of 187 consecutive patients with PNESs, 57 patients had PNESs and epilepsy (PNES+E), and 130 patients, PNESs alone. The diagnosis of additional epilepsy was based on ictal (video‐) EEG or on the critical assessment of all clinical data by an experienced epileptologist. Retrospective review of all available EEG reports showed that 92.9% of patients in the PNES+E and 53.8% in the PNES‐only group had one or more abnormal EEGs (median number of EEGs per patient, three; range, one to 42). In the PNES‐only group, EEG changes were nonspecific in 42.3% of patients. Only 50 of 130 patients with PNESs alone had no other clinically recognizable cause of EEG disturbance and entered the controlled study. In this study, 18% of patients and 10% of controls had abnormal EEGs. The frequency of epileptiform EEG changes was similar to that in previous population studies in both groups (2.0%).

Conclusions: PNESs often occur in patients with organic brain disease. Even in patients with PNESs alone and no clinically recognizable cause of EEG disturbance, nonspecific abnormalities are found 1.8 times as often as in healthy controls. Interictal EEG changes are common in patients with PNESs and, in isolation, should not be interpreted as evidence of epilepsy.
Nonsymptomatic Generalized Epilepsy in Children Younger than Six Years: Excellent Prognosis, but Classification Should Be Reconsidered after Follow‐up: The Dutch Study of Epilepsy in Childhood
Authors: Middeldorp C. M. , Geerts A. T. , Brouwer O. F. , Peters A. C. B. , Stroink H. , Van Donselaar C. A. , Arts W. F. M.
Published: March 2003

Summary:  Purpose: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy.

Methods: Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow‐up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis.

Results: The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic–clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow‐up, 75% had a TR of >6 months after 2 years, and 85% a TR of ≥1 year after 5 years.

Conclusions: In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent.
Herbal Remedies, Dietary Supplements, and Seizures
Authors: Tyagi Alok , Delanty Norman
Published: March 2003

Summary: The use of herbal remedies and dietary supplements is widespread throughout the world, and use may be increasing. These are taken for a wide range of perceived benefits, such as energy and memory enhancement and treatment of specific conditions. Individuals with and without epilepsy may use these substances and may not inform their treating physician unless specifically asked. Inquiry about herbal medicine and dietary supplement intake should now be part of routine clinical history taking. Anecdotal accounts suggest that some herbal substances may have anticonvulsant effect, but randomised double‐blind controlled trails are lacking. Alternatively many herbals and dietary supplements may predispose to seizures in individuals without epilepsy and worsen seizure control in those with epilepsy. In this article, we review the potential anticonvulsant and proconvulsant effects of herbal remedies and dietary supplements and discuss the potential interaction between these herbal substances and conventional anticonvulsant medications.
Levetiracetam, a New Antiepileptic Agent: Lack of In Vitro and In Vivo Pharmacokinetic Interaction with Valproic Acid
Authors: Coupez René , Nicolas Jean‐Marie , Browne Thomas R.
Published: March 2003

Summary:  Purpose: The novel antiepileptic drug (AED) levetiracetam (LEV; Keppra) has a wide therapeutic index and pharmacokinetic characteristics predicting limited drug‐interaction potential. It is indicated as an add‐on treatment in patients with epilepsy, and thus coadministration with valproic acid (VPA) is likely. These studies were performed to determine whether coadministration of LEV with VPA might result in pharmacokinetic interactions.

Methods: In vitro assays were performed to characterize the transformation of LEV into its main in vivo metabolite UCB L057. The reaction was examined for its sensitivity to clinically relevant concentrations of VPA. An open‐label, one‐way, one‐sequence crossover clinical trial was conducted in 16 healthy volunteers to assess further the possibility of any relevant pharmacokinetic interaction.

Results: Human whole blood and, to a lesser extent, human liver homogenates were demonstrated to hydrolyze LEV to UCB L057, its main metabolite. The reaction possibly involves type‐B esterases and is not affected by 1 mM VPA (i.e., 166 μg/ml). Pharmacokinetic parameters of a single dose of LEV (1,500 mg) coadministered with steady‐state concentrations of VPA (8 days of 500 mg, b.i.d.) did not differ significantly from the pharmacokinetics of LEV administered alone [area under the curve (AUC) of 397 and 400 μg/h/ml, respectively]. Furthermore, LEV did not affect the steady‐state pharmacokinetics of VPA.

Conclusions: These findings suggest the absence of a pharmacokinetic interaction between VPA and LEV during short‐term administration, and suggest that dose adjustment is not required when these two drugs are given together.