bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsant Profile of Valrocemide (TV1901): A New Antiepileptic Drug
Authors: Isoherranen Nina , Woodhead José H. , White H. Steve , Bialer Meir
Published: March 2003

Summary:  Purpose: We sought to investigate the anticonvulsant activity of the new antiepileptic drug (AED), valrocemide or TV1901 (VGD) in various animal (rodent) models of human epilepsy to determine its anticonvulsant profile and safety margin.

Methods: VGD was administered intraperitoneally to CF no. 1 mice and orally or intraperitoneally to Sprague–Dawley rats. The anticonvulsant activity of VGD was examined in nine different animal models of epilepsy for its ability to block electrically, chemically, or sensorily induced seizures.

Results: In mice VGD afforded complete protection against maximal electroshock (MES)‐, pentylenetetrazole‐, picrotoxin‐, and bicuculline‐induced seizures and 6‐Hz “psychomotor” seizures with median effective dose (ED50) values of 151, 132, 275, 248, and 237 mg/kg, respectively. VGD was also effective in preventing sound‐induced seizures in Frings audiogenic‐seizure susceptible mice (ED50, 52 mg/kg). The median neurotoxic dose in mice was 332 mg/kg. After oral administration to rats, VGD was active in the MES test, with an ED50 of 73 mg/kg, and the median neurotoxic dose was 1,000 mg/kg. Intraperitoneal administration of 300 mg/kg of VGD to hippocampal kindled Sprague–Dawley rats blocked generalized seizures and shortened the afterdischarge duration significantly. VGD also provided complete protection from focal seizures in the corneally kindled rats (ED50,161 mg/kg).

Conclusions: The results obtained in this study suggest that VGD has a broad spectrum of anticonvulsant activity and promising potential as a new AED.
The Ontogeny of Partial Seizures in Infants and Young Children
Authors: Nordli Douglas R. , Kuroda Maxine M. , Hirsch Lawrence J.
Published: March 2003

Summary:  Purpose: To describe the clinical manifestations of partial seizures in the pediatric population as a function of age.

Methods: Using the database of the pediatric epilepsy monitoring unit (Children's Hospital of New York), clinical and EEG characteristics of partial seizures were distributed by age groups 0–2, 2–6, and 6+ years for 123 patients who had at least one such seizure with a clear EEG correlate during their admission. χ2 tests for trend were used to examine clinical and EEG features as a function of age.

Results: The frequency of aura, limb automatisms, dystonic posturing, secondary generalization, and unresponsiveness increased with age, whereas asymmetric clonus and symmetric tonic posturing decreased with age. There were no clear changes in the types of EEG ictal patterns observed with age; however, partial seizures emanating from the anterior regions of the brain tended to increase with age, whereas those from the posterior regions tended to decrease with age.

Conclusions: Important differences exist in the clinical expression of seizures between young children and adults. These findings will contribute to a better understanding of ictal ontogeny that will promote more accurate classification of seizures and of the epilepsies in young patients. Such efforts can be used to identify young patients for focal epilepsy surgery and to select appropriate anticonvulsive medications.
Destruction of Peripheral C‐Fibers Does Not Alter Subsequent Vagus Nerve Stimulation‐Induced Seizure Suppression in Rats
Authors: Krahl Scott E. , Senanayake Shayani S. , Handforth Adrian
Published: March 2003

Summary:  Purpose: Early animal studies of the therapeutic mechanisms of vagus nerve stimulation (VNS) suggested that seizure suppression requires maximal activation of small, unmyelinated vagal C fibers. However, effective therapeutic stimulation parameters appear to be subthreshold for these fibers in humans, and there are no clinical reports of the autonomic side effects that would be expected if these fibers were maximally activated. We report here that selective destruction of C fibers with capsaicin does not affect VNS‐induced seizure suppression in rats.

Methods: Rats were pretreated with capsaicin or vehicle in three injections over a 2‐day period. A cuff electrode was later implanted on the left cervical vagus nerve. Two days after surgery, VNS was given to half of the capsaicin‐ and vehicle‐treated rats. The remaining rats were connected to the stimulator but did not receive VNS. Thirty seconds after VNS onset, seizures were induced by pentylenetetrazol (PTZ), and seizure severity was measured. Two days later, the reciprocal VNS treatment was given, and PTZ‐induced seizure severity was again measured.

Results: VNS effectively reduced seizure severity in both capsaicin‐ and vehicle‐treated rats as compared with their non‐VNS baselines.

Conclusions: These results indicate that activation of vagal C fibers is not necessary for VNS‐induced seizure suppression.
Estimating the Costs of Epilepsy: An International Comparison of Epilepsy Cost Studies
Authors: Kotsopoulos Irene A. W. , Evers Silvia M. A. A. , Ament André J. H. A. , De Krom Marc C. T. F. M.
Published: March 2003

Summary:  Purpose: To compare systematically the national and per capita estimates of the cost of epilepsy in different countries.

Methods: Studies for this literature review were selected by conducting a Medline literature search from January 1966 to March 2000. Key methodologic, country‐related, and monetary issues of the selected epilepsy cost studies were evaluated to compare their direct cost estimates and to explore their distribution. The results of the selected studies were made comparable by converting them with different types of conversion factors and expressing them as a proportion of the national expenditure on health care.

Results: Ten epilepsy cost studies were reviewed. The proportion of national health care expenditure on epilepsy shows a range of 0.12–1.12% or 0.12–1.05% depending on the type of conversion factor. The list of cost components included in the estimation of the direct costs of epilepsy differs from study to study. A comprehensive list is associated with a decrease in the contribution of drug and hospital costs to the total direct costs of epilepsy.

Conclusions: This study highlights the importance of studying the economic consequences of epilepsy and of interpreting the results on the international level. The results of epilepsy cost studies can provide insight into the distribution of the costs of epilepsy and the impact of epilepsy on the national expenditure on health care.
The Costs of Childhood Epilepsy in Italy: Comparative Findings from Three Health Care Settings
Authors: Guerrini R. , Battini R. , Ferrari A. R. , Veggiotti P. , Besana D. , Gobbi G. , Pezzani M. , Berta E. , Tetto A. , Beghi E. , Monticelli M. L. , Tediosi F. , Garattini L. ,   theEpilepsy Collaborative Study Group, Russo S. , Rasmini P. , Amadi A. , Quarti P. , Fabrizzi R.
Published: March 2003

Summary:  Purpose: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services].

Methods: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non–drug‐resistant epilepsy; and (d) those with drug‐resistant epilepsy. Over a 12‐month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency.

Results: A total of 189 patients was enrolled by two teaching‐CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug‐resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non–drug‐resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching‐CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs.

Conclusions: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.
Vigabatrin Visual Toxicity: Evolution and Dose Dependence
Authors: Malmgren Kristina , Ben‐Menachem Elinor , Frisén Lars
Published: March 2003

Summary:  Purpose: To investigate the prevalence and prognosis of visual field defects (VFDs) in epilepsy patients with and without vigabatrin (VGB) treatment; to investigate the possible relationship between VFDs and cumulative VGB dose, and to characterise the evolution of VFDs.

Methods: A cohort of 155 presurgical candidates who had undergone full‐field Goldmann perimetry (GP) was studied, 99 (64%) of whom had been treated with VGB. All GPs were reevaluated in 1998 by one experienced examiner, blinded to medication. Duration of treatment and total VGB dose were related to perimetric results.

Results: Twenty‐five (16%) of the 155 patients had VFDs: Nineteen (19%) of the 99 VGB‐treated patients, and six (11%) of the 56 patients unexposed to VGB. VGB‐treated patients with VFDs had been treated significantly longer than those without VFDs. Cumulative VGB dose could be calculated for 84 patients. The prevalence of VFDs increased significantly with increasing total VGB‐dose, from 4% in the 51 patients who had been exposed to ≤1 kg VGB, to 75% in the eight patients with a total dose of 3–5 kg of VGB. Sixteen VGB‐treated patients were reexamined 2–10 years later. In the 12 where evaluation was possible, all still had VFDs, which had worsened in five cases (42%) and improved in none.

Conclusions: This study indicates a strong relationship between VFDs and duration and total dose of VGB. VFDs were irreversible and in a substantial percentage progressive. Similar VFDs may, however, also be found in patients unexposed to VGB. A model of the evolution of the VFDs in VGB toxicity is introduced, and a new simple visual field test is proposed.
Classification of Epileptic Seizures: A Comparison of Two Systems
Authors: Parra Jaime , Augustijn Paul B. , Geerts Yvette , Van Emde Boas Walter
Published: March 2003

Summary:  Purpose: Extensive experience with video‐EEG seizure monitoring, notably in the setting of epilepsy surgery programs, has exposed the limited value of the current International Classification of Epileptic Seizures (ICES) for providing relevant localizing information. To overcome this limitation, a Semiologic Seizure Classification (SSC) has recently been proposed. This study aimed to assess and to compare the usefulness and reliability of both systems in the setting of a tertiary epilepsy center.

Methods: Three epileptologists independently reviewed video‐taped seizures, randomly selected from the archive of the Epilepsy Monitoring Unit. They were blinded to the EEG findings and final diagnosis and classified all seizures according to both classifications.

Results: One hundred thirty‐eight seizures from 60 patients (age range, 2–59 years) were reviewed (maximum, three seizures per patient). Fifty‐five seizures from 20 patients were recorded in the setting of presurgical evaluations, and the remainder as part of regular diagnostic evaluations. The average interobserver agreement was higher for SSC (63.3%, κ = 0. 56) than for ICES (38.6%, κ = 0.41). Some categories of SSC, such as hypermotor or automotor, had the best interobserver agreement, and were strongly correlated with the anatomic localization of the seizures (frontal and temporal lobe, respectively). All reviewers agreed that SSC provided a better description of the seizures than did ICES, in 60% of the patients.

Conclusions: SSC provides a more comprehensive picture of epileptic seizures than does ICES, notably in patients with localized epilepsy syndromes, and appears to be very useful and reliable, particularly in the setting of specialized epilepsy centers.
Neuropathological Findings in a Patient with Epilepsy and the Parry–Romberg Syndrome
Authors: DeFelipe Javier , Segura Tomás , Arellano Jon I. , Merchán Angel , DeFelipe‐Oroquieta Jesús , Martín Pilar , Maestú Fernando , Y Cajal Santiago Ramón , Sánchez Alicia , Sola Rafael G.
Published: March 2003

Summary:  Purpose: The Parry–Romberg syndrome is an unusual disorder frequently associated with epilepsy. The origin of this disease, and the cause of epilepsy, are unknown. This study is the first reported case of the Parry–Romberg syndrome, with intractable temporal lobe epilepsy, in which detailed microanatomic analyses have been performed on resected brain tissue obtained after surgical intervention.

Methods: Standard histopathologic methods and correlative light and electron microscopy, combined with immunocytochemical techniques, were used to study in detail the synaptic microorganization of the resected hippocampal formation.

Results: After surgery, the patient was seizure free (follow‐up period of 4 years and 7 months). The resected temporal lobe showed a variety of dramatic microanatomic alterations (small groups of ectopic cells, neuronal loss, gliosis, and activated microglial cells) in mesial structures, including the entorhinal cortex, subiculum, and dentate gyrus. At the electron‐microscopic level, we found that in the dentate gyrus, the number of synapses in the cell‐sparse region adjacent to the ectopic mass of neurons was almost twice that found in the molecular and polymorph cell layers, indicating the intrusion of neuritic processes and synapse formation. In addition, the symmetrical axosomatic synapses characteristically found on granule cells, which are likely derived from γ‐aminobutyric acid (GABA)ergic inhibitory basket cells, were not observed.

Conclusion: The complete seizure relief after surgery suggests that the pacemaker region(s) of seizure activity were within the resected tissue. However, we do not know which of the multiple neuropathologic findings reported here were the primary cause of seizure activity. Nevertheless, the changes found in the dentate gyrus circuitry appear to be among the most important alterations that would lead to epilepsy.
Long‐term Outcome Is Unchanged by Antiepileptic Drug Treatment after a First Seizure: A 15‐year Follow‐up from a Randomized Trial in Childhood
Authors: Camfield Peter , Camfield Carol , Smith Stephanie , Dooley Joe , Smith Edythe
Published: March 2003

Summary:  Purpose: In 1989 we reported that 1 year of daily treatment with carbamazepine (CBZ) significantly reduced the recurrence rate after a first afebrile seizure in children compared with no treatment in a randomized open trial. We sought to determine if the long‐term clinical course and rate of remission were changed by treatment starting after the first seizure.

Methods: Participants of the original trial (14 CBZ, 17 no medication) were contacted in 2001.

Results: Sixteen controls and 10 CBZ (84%) cases were followed up for 15 years. After randomization and follow‐up, 12 controls and five treated patients had at least one more seizure (p = NS). For those with recurrences, the number of recurrences appeared to be the same in both groups. Number of medications used was also the same. Terminal remission (>2 years seizure free with or without medication) was achieved by eight (80%) of 10 CBZ and 14 (88%) of 16 controls, and terminal remission off medication in six (60%) of 10 CBZ (p = NS).

Conclusions: Based on this small study with long follow‐up, it appears that for children treated with CBZ after a first seizure, the subsequent clinical course and remission rates are not improved in comparison with a no‐treatment strategy. Delaying treatment after a first seizure appears defensible.
Metabolic and Electrophysiological Alterations in Subtypes of Temporal Lobe Epilepsy: A Combined Proton Magnetic Resonance Spectroscopic Imaging and Depth Electrodes Study
Authors: Guye Maxime , Le Fur Yann , Confort‐Gouny Sylviane , Ranjeva Jean‐Philippe , Bartolomei Fabrice , Régis Jean , Raybaud Charles A. , Chauvel Patrick , Cozzone Patrick J.
Published: March 2003

Summary:  Purpose: This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging (1H‐MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE).

Methods: Twenty‐five subjects were investigated, including 15 controls and 10 patients with drug‐resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two 1H‐MRS imaging acquisitions associated with two single‐voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N‐acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann–Whitney U test.

Results: N‐Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p < 0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p > 0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures.

Conclusions: These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural alterations in TLE.
The Use of Stereotactic Radiosurgery to Treat Intractable Childhood Partial Epilepsy
Authors: Dunoyer Catalina , Ragheb John , Resnick Trevor , Alvarez Luis , Jayakar Prasanna , Altman Nolan , Wolf Aizik , Duchowny Michael
Published: March 2003

Summary: Purpose:Although conventional surgery is presently used to treat seizures of temporolimbic and neocortical origin, deep‐seated lesions are often associated with morbidity. Stereotactic radiosurgery is a noninvasive procedure that effectively treats patients with vascular malformations and brain tumors, but its efficacy for epileptogenic foci is limited, especially in children.

Methods:Between 1995 and 1999, four candidates who had medically uncontrolled seizures and localized seizure foci were selected for stereotactic radiosurgery, with a mean age of 9.75 years at the time of surgery (range, 4–17 years). Seizure foci were identified on the basis of ictal and interictal video‐EEG. Magnetic resonance (MR) images were obtained before and after surgery. Ictal single‐photon emission computed tomography (SPECT) was performed by using stabilized hexamethyl‐propyleneamine oxime (HMPAO; 300 microcuries/kg) with early injection after electrographic ictal onset. The clinical features of the patients are given. All radiosurgical procedures were performed with the gamma knife unit with the Leksell stereotactic frame, stereotactic MRI imaging, and the Gamma Plan workstation. Seizure outcome was scored according to Engel's classification.

Results:Two patients had hypothalamic hamartoma (HH), and two had neocortical epilepsy. At mean follow‐up of 39.2 months (range, 26–69 months), two patients were seizure free, one with a HH and one with a suggestive developmental tumor in the insular cortex by MRI findings. The other patient with HH had 90% reduction of seizures. One patient with a widespread seizure focus that involved the motor strip was unimproved. The two patients with HH also exhibited markedly improved neurobehavioral status after surgery. There were no significant complications of radiosurgical therapy.

Conclusions:Our findings suggest that gamma knife surgery is a potentially valuable treatment modality for children with medically intractable epilepsy due to a well‐localized seizure focus that is difficult to excise by conventional techniques or for whom they are deemed unsuitable. More widespread application in childhood epilepsy should be investigated in larger series.
Increased Bone Turnover in Prepubertal, Pubertal, and Postpubertal Patients Receiving Carbamazepine
Authors: Verrotti Alberto , Greco Rita , Latini Giuseppe , Morgese Guido , Chiarelli Francesco
Published: March 2003

Summary:  Purpose: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy.

Methods: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex‐ and age‐matched healthy children.

Results: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy‐terminal propeptide of type I procollagen (PICP), amino‐terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy‐terminal telopeptide of type I collagen (ICTP) and the urinary cross‐linked N‐telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism.

Conclusions: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.
Quantitative Analysis of Benzodiazepine Receptor in Temporal Lobe Epilepsy: [125I]Iomazenil Autoradiographic Study of Surgically Resected Specimens
Authors: Sata Yoshimi , Matsuda Kazumi , Mihara Tadahiro , Aihara Masao , Yagi Kazuichi , Yonekura Yoshiharu
Published: March 2003

Summary:  Purpose: To evaluate the changes of the inhibitory neurotransmitter receptor system related to epileptogenesis by measuring central benzodiazepine receptors (BZDRs) in surgically resected specimens of temporal lobe epilepsy by using [125I]iomazenil autoradiography.

Methods: Surgically resected specimens were obtained from 66 temporal lobe epilepsy patients [51 with mesial temporal lobe epilepsy (MTLE) and 15 with non‐MTLE] receiving no BZDs and seven MTLE patients receiving BZDs. BZDR densities in brain sections were measured by using [125I]iomazenil autoradiography. Cell densities were measured from cresyl violet–stained sections.

Results: Compared with non‐MTLE patients, non–BZD‐treated MTLE patients showed remarkable reduction of BZDR density in the pyramidal cell region of cornu ammonis (CA) 1, CA3, and CA4, and a smaller but significant reduction in CA2 and the molecular and granule cell layers of dentate gyrus (mDG). In the MTLE group, the BZDR density in the mDG correlated with that in lateral cortex. Significant correlations between BZDR density and cell density were found in all hippocampal regions. A significant difference in BZDR density/cell‐density ratio was observed in CA1 region between MTLE and non‐MTLE. BZD‐treated patients tended to have lower BZDR densities than did non–BZD‐treated patients, although the differences did not reach significance. In all MTLE cases, [123I]iomazenil singlephoton emission computed tomography (SPECT) showed decreased BZDR binding in MTL.

Conclusions: In MTLE, BZDR densities decreased parallel to reduction in cell density in most hippocampal subfields, but BZDR density appeared to decrease in excess of neuron loss in CA1. [123I]Iomazenil SPECT might be useful for detecting in vivo changes of BZDR density.
Morbidity and Accidents in Patients with Epilepsy: Results of a European Cohort Study
Authors: Beghi Ettore , Cornaggia Cesare ,   the RESt‐1 Group
Published: March 2003

Summary: Purpose:To assess the risk of illnesses and accidents in patients with epilepsy and to evaluate the proportion of those risks attributable to epilepsy.

Methods:Nine hundred fifty‐one referral patients with idiopathic, cryptogenic, or remote symptomatic epilepsy and 909 matched controls (relatives or friends) were followed up prospectively for 1–2 years in eight European countries (Italy, Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient and control received a diary to keep notes regarding any illness or accident. Patients with epilepsy specifically recorded relations with seizures.

Results:Six hundred forty‐four patients recorded 2,491 illnesses compared with 1,665 illnesses in 508 controls. The cumulative probability of illness in patients was 49% by 12 months and 86% by 24 months (controls, 39 and 75%; p < 0.0001). One hundred ninety‐nine patients and 124 controls had 270 and 140 accidents, respectively. The cumulative probability of accident in the cases was 17 and 27% by 12 and 24 months (controls, 12 and 17%; p < 0.0001). The chance of two or more illnesses or accidents was modestly but significantly greater in the patients. Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24% of accidents were seizure related. When illnesses and accidents related to seizures were excluded, the chance of illnesses and accidents was fairly similar in the two groups.

Conclusions:Patients with idiopathic, cryptogenic, or remote symptomatic epilepsy have a moderately higher risk of illnesses and accidents than do the general population. With few exceptions, the events are trivial. When seizure‐related events are excluded, patients with epilepsy are not at any significantly higher risk of illnesses and accidents.
Contribution of SISCOM Imaging in the Presurgical Evaluation of Temporal Lobe Epilepsy Related to Dysembryoplastic Neuroepithelial Tumors
Authors: Valenti M. P. , Froelich S. , Armspach J. P. , Chenard M. P. , Dietemann J. L. , Kerhli P. , Marescaux C. , Hirsch E. , Namer I. J.
Published: March 2003

Summary: Purpose:Dysembryoplastic neuroepithelial tumors (DNTs) are a group of glioneuronal supratentorial and intracortical lesions often associated with the early onset of intractable and crippling partial seizures. They are characterized by their location, multinodular architecture, and heterogeneous cell composition, with a specific glioneuronal element in the specific form. Foci of cortical dysplasia may be associated with the tumoral lesion, and identifying the presence and the extent of cortical dysplasia is not always easy on magnetic resonance images (MRIs). The purpose of this article is to evaluate, retrospectively, the usefulness of ictal single‐photon emission computed tomography (SPECT) imaging to assess the presence and the extent of cortical dysplasia associated with DNTs in nine patients with intractable temporal lobe epilepsy related to histopathologically confirmed DNTs.

Methods:The results of the subtraction of ictal and interictal SPECT coregistered to MRI (SISCOM) were compared with the results of the examinations of pathological material after surgery.

Results:SISCOM showed a strongly hyperperfused area corresponding anatomically to electroclinical abnormalities and to the location of DNTs on MRI. A circumscribed hyperperfusion was present in DNTs without cortical dysplasia, limited to the location of the tumor on MRI. In cases of associated cortical dysplasia, a widespread hyperperfusion including areas corresponding to normal perilesional regions on MRI was found.

Conclusions:SISCOM, used among presurgical investigations, contributes to detecting cortical dysplasia associated with DNTs. Concordance between the symptomatogenic zone (defined from the medical history and electroclinical data), MRI scans, SISCOM pattern, and complete resection of the epileptic zone was predictive of a good postsurgical outcome.
Recurrent Seizures and Behavior Problems in Children with First Recognized Seizures: A Prospective Study
Authors: Austin Joan K. , Dunn David W. , Caffrey Helena M. , Perkins Susan M. , Harezlak Jaroslaw , Rose Douglas F.
Published: March 2003

Summary:  Purpose: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new‐onset seizures.

Methods: Subjects were 224 children with new‐onset seizures (aged 4–14 years) and 159 siblings (4–18 years). Caregiver's ratings of the behavior were collected 4 times: at baseline, and at 6, 12, and 24 months. During the 2‐year period, 163 (73%) children had at least one additional seizure, and 61 (27%) had none. Data were analyzed by using repeated measures analysis of variance both with and without covariates [site, age, gender, race, caregiver education (years), and seizure medications].

Results: On average, children had higher CBCL Total and Internalizing Behavior Problems scores across all times when experiencing recurrent seizures than when not experiencing recurrent seizures (Total Problems, p = 0.041, controlling for demographics and seizure medications). Siblings had significantly lower Total and Internalizing Problems scores than both children experiencing (Total Problems adjusting for covariates, p = 0.0001) and not experiencing recurrent seizures (p = 0.0004). Externalizing Problems scores were not significantly different among children with recurring seizures, children without recurring seizures, and siblings.

Conclusions: Recurrent seizures significantly predicted behavior problems very early in the course of a seizure condition, even when key child, demographic, and seizure variables were controlled. Explanations for these findings include the possibilities that both seizures and behavior problems are caused by an underlying neurological disorder, that seizures per se disrupt behavior, or that children have negative psychological responses to seizure activity.
Cognitive Skills in Children with Intractable Epilepsy: Comparison of Surgical and Nonsurgical Candidates
Authors: Smith Mary Lou , Elliott Irene M. , Lach Lucyna
Published: March 2003

Summary:  Purpose: To compare neuropsychological performance of two groups of children with intractable epilepsy: those who are surgical candidates, and those who are not.

Methods: Intelligence, verbal memory, visual memory, academic skills, and sustained attention were measured in children aged 6–18 years. The effects of number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset, and duration of seizure disorder were examined.

Results: Both groups had high rates of impairment. Group differences were found only on the verbal memory task. Children who experienced seizures in clusters had higher IQ, reading comprehension, and arithmetic scores. Age at seizure onset and proportion of life with seizures were related to IQ. Performance did not vary with AED monotherapy versus polytherapy.

Conclusions: Few differences exist in cognitive performance between children with intractable seizures who are and those who are not surgical candidates. These findings suggest that children who are not surgical candidates can serve as good controls in studies on cognitive outcome of surgery.
Public Awareness, Attitude, and Understanding of Epilepsy in Hong Kong Special Administrative Region, China
Authors: Fong Chung‐yan Gardian , Hung Anchor
Published: March 2003

Summary:  Purpose: Because of the nature of the epileptic seizure, the social stigma attached to epilepsy is a major handicap to persons with epilepsy compared with the disability associated with seizures or the side effects from medications. Measuring the awareness, attitude, and understanding of epilepsy is the first step in alleviating discrimination.

Methods: We conducted a face‐to‐face questionnaire interview survey in five different locations (HKSAR) that represented the population structure, administrative function, and occupations of inhabitants. Subjects with epilepsy or with relatives who had epilepsy were excluded.

Results: We interviewed 1,128 subjects; 58.2% had heard about epilepsy before. Of these, 55% had witnessed one or more epileptic seizure, and 18.9% knew one or more persons with epilepsy; 52.7% would put an object into a patient's mouth during an epileptic seizure to prevent injury of the tongue (32.2% learned this from a local television program), and 94.1% agreed that persons with epilepsy could be married. However, only 72.5% considered pregnancy to be appropriate; 11.2% would not let their children play with others with epilepsy; 32.2% would not allow their children to marry persons with epilepsy. Employers (22.5%) would terminate the employment contract after an epileptic seizure in an employee with unreported epilepsy.

Conclusions: This study documented the public attitude toward epilepsy in HKSAR; although it was more negative than that in Western societies, it was more positive than that of the Chinese in China or Taiwan. We suggest that more effort be made to improve public awareness of, attitude toward, and understanding of epilepsy through school education and epilepsy‐related organizations in HKSAR.
Attention Deficits Are Not Characteristic of Schoolchildren with Newly Diagnosed Idiopathic or Cryptogenic Epilepsy
Authors: Oostrom K. J. , Schouten A. , Kruitwagen C. L. J. J. , Peters A. C. B. , Jennekens‐Schinkel A. ,   Schinkelfor the Dutch Study of Epilepsy in Childhood (DuSECh)
Published: March 2003

Purpose:To compare problems of attention in schoolchildren with newly diagnosed idiopathic or cryptogenic epilepsy with those in healthy classmates.

Methods:A computerized battery of tasks comprised Reaction Time (RT) measurement, Trail making (Color Trails 1 and 2), Manual Tapping and Steadiness, and a newly developed task of sustained attention (Balloon Piercing).

Subjects:Fifty‐one children with epilepsy (age 7–16 years) and 48 gender‐ and age‐matched classmates were assessed thrice: within 48 h after diagnosis [before start of antiepileptic drugs (AEDs)], and 3 and 12 months later. Significantly more children with epilepsy (51%) than control children (27%) had required special educational assistance at school.

Results:Children with epilepsy could not be distinguished from controls in execution times or motor speed. However, errors were more frequent among patients in a “go–no‐go” RT task, and errors of omission in a task requiring sustained attention. Within the group of children with epilepsy, those with prior school or behavior difficulties and those whose parents reacted maladaptively to the onset and diagnosis of epilepsy performed worse than those without these adversities, in the sense that their RT increased inordinately with increasing task difficulty. Epilepsy‐related variables did not explain any variance. Transient inordinately poor performances were found in 69% of patients and 40% of controls.

Conclusions:Children with newly diagnosed “epilepsy only” do not have persistent attention deficits. AED treatment has no detrimental effect on attention. Prior school and behavior difficulties and a maladaptive reaction to the onset of epilepsy rather than epilepsy variables are related to decreased attentional efficiency.
Topiramate Enhances the Risk of Valproate‐associated Side Effects in Three Children
Authors: Longin Elke , Teich Martin , Koelfen W. , König Stefan
Published: March 2003

Summary:  Purpose: We present three children with severe therapy‐refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM).

Methods: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia.

Results: All children recovered completely after discontinuation of VPA or TPM.

Conclusions: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM.
Gabapentin versus Lamotrigine Monotherapy: A Double‐blind Comparison in Newly Diagnosed Epilepsy
Authors: Brodie Martin J. , Chadwick David W. , Anhut Henning , Otte Andreas , Messmer Silke‐Lo , Maton Stephen , Sauermann Wilhelm , Murray Guta , Garofalo Elizabeth A. ,   for the Gabapentin Study Group 945‐212
Published: March 2003

Summary:  Purpose: This randomised, double‐blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy.

Methods: Patients with partial seizures with and/or without secondary generalization or primary generalized tonic–clonic seizures were randomized to either GBP or LTG. During 2‐ and 6‐week titration periods, respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the subsequent 24‐week maintenance phase, the dose could be adjusted based on seizure control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300 mg/day for LTG. The primary end point was time to exit, a composite of efficacy and tolerability. Evaluable patients were used for the primary efficacy analysis, whereas tolerability was examined on an intent‐to‐treat basis.

Results: A total of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the evaluable population. Nineteen patients in each group had an exit event. The median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was estimated as 1.043 (90% confidence intervals, 0.602–1.809). Overall, 106 (71.6% of the evaluable population) GBP‐treated and 96 (67.1%) LTG‐treated patients completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%) taking LTG remained seizure free during the final 12 weeks of treatment. Only 14 (8.9%) GBP‐treated patients and 15 (9.9%) LTG‐treated patients withdrew because of study drug–related adverse events.

Conclusions: GBP and LTG monotherapy were similarly effective and well tolerated in patients with newly diagnosed epilepsy.
Epileptogenicity of Focal Malformations Due to Abnormal Cortical Development: Direct Electrocorticographic–Histopathologic Correlations
Authors: Boonyapisit Kanokwan , Najm Imad , Klem George , Ying Zhong , Burrier Candice , LaPresto Eric , Nair Dileep , Bingaman William , Prayson Richard , Lüders Hans
Published: March 2003

Summary:  Purpose: Malformations due to abnormal cortical development (MCDs) are common pathologic substrates of medically intractable epilepsy. The in situ epileptogenicity of these lesions as well as its relation to histopathologic changes remains unknown. The purpose of this study was to correlate the cellular patterns of MCDs with the expression of focal cortical epileptogenicity as assessed by direct extraoperative electrocorticographic (ECoG) recordings by using subdural grids.

Methods: Fifteen patients with drug‐resistant focal epilepsy due to pathologically confirmed MCD who underwent subdural electrode placement for extraoperative seizure localization and cortical mapping between 1997 and 2000 were included in the study. Areas of interictal spiking and ictal‐onset patterns were identified and separated during surgery for further pathologic characterization (cellular and architectural). Three pathologic groups were identified: type I; architectural disorganization with/without giant neurons, type IIA; architectural disorganization with dysmorphic neurons, and type IIB; architectural disorganization, dysmorphic neurons, and balloon cells (BCs). The focal histopathologic subtypes of MCDs in cortical tissue resected were then retrospectively correlated with in situ extraoperative ECoG patterns.

Results: Cortical areas with histopathologic subtype IIA showed significantly higher numbers of slow repetitive spike pattern in comparison with histopathologic type I (p = 0.007) and normal pathology (p = 0.002). The ictal onset came mainly from cortical areas with histopathologic type IIA (nine of 15 patients). None of the seizures originated from neocortical areas that showed BC‐containing MCD (type IIB).

Conclusions: This study shows that areas containing BCs are less epileptogenic than are closely located dysplastic regions. These results suggest a possible protective effect of BCs or a severe disruption in the neuronal networks in BCs containing dysplastic lesions. Further studies are needed to elucidate the nature and the potential role(s) of balloon cells in MCD‐induced epileptogenicity.
Sexual Dysfunction and Sudden Death in Epileptic Male EL Mice: Inheritance and Prevention with the Ketogenic Diet
Authors: Todorova Mariana T. , Dangler Charles A. , Drage Michael G. , Sheppard Barbara J. , Fox James G. , Seyfried Thomas N.
Published: March 2003

Summary:  Purpose: The EL mouse is an animal model for multifactorial idiopathic epilepsy. Although EL mice have been studied extensively for >45 years, the etiology of male sudden death and its relation to seizures have not been defined. Here we investigated the cause of EL male sudden death and its relation to epilepsy.

Methods: For histopathologic analysis, the terminally ill EL mice (n = 15) were killed, and the tissues were fixed. Blood chemical composition was compared between the terminally ill EL (n = 9) and the healthy age‐matched EL (n = 17) and DDY (n = 11) males. To determine the effect of the ketogenic diet (KD) on sudden male death, young male EL mice (P30) were randomly separated into two groups that were fed ad libitum with either Agway lab chow (control n = 38) or with the KD (treated, n = 39) for 5 months. The genetic predisposition to sudden death was analyzed in the backcross generation (n = 106) of a cross between EL and the nonepileptic ABP strains.

Results: Sudden death coincided with the onset of seizures (70–80 days) and affected 94% of male EL mice by age 300 days. Urethral plugs were observed histologically in 13 of 15 longitudinally sectioned penises. Concentrations of blood urea nitrogen, creatinine, phosphorus, and calcium in the terminally ill mice were significantly elevated when compared with those of healthy animals. None of the mice treated with the KD experienced sudden death, whereas 15 (39%) of the untreated control mice died by age 5 months. The sudden death in male EL mice was inherited as an autosomal recessive sex‐limited lethal trait.

Conclusions: The cause of sudden death in male EL mice arises from abnormal ejaculation, which produces a urethral plug with consequent urinary retention and acute severe uremia. The coincident onset of seizures and sudden death in EL males suggests that a sexual dysfunction is associated with epilepsy in this model.
Talampanel, a New Antiepileptic Drug: Single‐ and Multiple‐dose Pharmacokinetics and Initial 1‐Week Experience in Patients with Chronic Intractable Epilepsy
Authors: Langan Yvonne M. , Lucas Richard , Jewell Haley , Toublanc N. , Schaefer H. , Sander Jasemire W. A. S. , Patsalos Philip N.
Published: March 2003

Summary:  Purpose: Talampanel (LY300164), a potent and selective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐receptor antagonist, is a potential new antiepileptic drug (AED). This study examines the single‐ and multiple‐dose pharmacokinetics, safety, and tolerability of talampanel in patients with intractable epilepsy and assesses the potential for pharmacokinetic interaction.

Methods: Eleven of 14 patients entered into the study completed. Fourteen patients were evaluated for safety, 13 patients were used in the single‐dose, and 11 patients in the multiple‐dose pharmacokinetic analysis. Each patient initially received a single 35‐mg dose of talampanel followed by the measurement of pharmacokinetic profiles. A 21‐day t.i.d. dosing regimen was then determined for each patient based on his or her initial pharmacokinetic profile. Adverse events were recorded by patients or their carers.

Results: After oral ingestion, talampanel was rapidly absorbed, with maximal plasma concentrations achieved within 1–3 h. Talampanel concentrations in patients taking enzyme‐inducing AEDs were 50% lower than those seen in healthy volunteers. Mean talampanel t1/2 values were 3.0 h compared with 4.2 h in healthy volunteers. After multiple‐dose and steady‐state, talampanel t1/2 values were increased to 5.6 h Talampanel and valproic acid (VPA) appear to inhibit each other's metabolism mutually. Talampanel had no effect on plasma concentrations of other AEDs. Multiple‐dose talampanel administration was associated with nonlinear pharmacokinetics. No serious adverse events were reported; the most frequently reported being dizziness, ataxia, drowsiness, and headaches

Conclusions: Talampanel dosing strategies may be reliant on concomitant AED medication, as enzyme‐inducing AEDs enhance, whereas VPA inhibits its metabolism. Talampanel was well tolerated, although adverse events occurred at lower doses compared with those in healthy subjects, probably because of the additive effect of concomitant AEDs.
Prognostic Implications of Seizure Recurrence in the First Year after Anterior Temporal Lobectomy
Authors: Radhakrishnan Kurupath , So Elson L. , Silbert Peter L. , Cascino Gregory D. , Marsh W. Richard , Cha Ruth H. , O'Brien Peter C.
Published: March 2003

Summary:  Purpose: Seizure recurrence after anterior temporal lobectomy (ATL) incites concerns of whether seizures will eventually be successfully controlled. Our study evaluated the prognostic significance of seizure recurrence in the first year after ATL.

Methods: The postoperative courses of 175 consecutive patients who had undergone ATL and had ≥2 years of follow‐up were studied. Recurrence was considered early if the first seizure occurred within 7 days after ATL and late if it occurred >7 days after ATL. Recurrent seizures were considered provoked when precipitating factors were present, such as interruption of antiepileptic drug (AED) intake. Subsequent outcome was determined at terminal follow‐up.

Results: Percentage of excellent outcome was comparable between patients whose initial recurrent seizures were auras or simple partial seizures and patients without seizure recurrence in the first year (86.7 vs. 93.1%; p ≥ 0.05). However, percentage of excellent outcome was less when the initial recurrent seizure was complex partial, either with or without secondary generalization (44.8%; p ≤ 0.01). Outcome was not different between early and late seizure recurrence (excellent in 41.7 vs. 55.7%; p ≥ 0.05). Nonetheless, patients with either early or late seizure recurrence were less likely to have excellent outcome than were patients with no seizure recurrence in the first year (p ≤ 0.001). Percentage of excellent outcome was best when patients were seizure free in the first year (93.1%), intermediate when initial recurrent seizure was provoked (72.0%), and worst when unprovoked (27.8%) (p ≤ 0.001).

Conclusions: In the first postoperative year, the type of initial recurrent seizure, whether aura or complex partial and whether provoked or unprovoked, is associated with long‐term prognosis in seizure control after ATL. The timing of the initial seizure recurrence is not as important.