bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Incidence of Epilepsy and Unprovoked Seizures in Multiethnic, Urban Health Maintenance Organizations
Authors: Annegers John F. , Dubinsky Stephanie , Coan Sharon Pasternak , Newmark Michael E. , Roht Lewis 
Published: August 2005

Summary: Purpose: Studies of the incidence of epilepsy are limited to a few populations in which new cases can be ascertained. Health maintenance organization (HmO) populations were studied to determine the incidence in a multiethnic, urban United States population. Methods: Cases of initial unprovoked seizure disorder or epilepsy while enrolled in an HMO between 1988 and 1994 were ascertained. Ethnicity was obtained from the medical records and was part of a nested case‐control study. Results: There were 197 incidence cases of epilepsy and 275 of initial unprovoked seizure diagnosis. The incidence rate in the age range 0–64 years was 35.5 per 100,000 for epilepsy and 50.9 for initial unprovoked seizure. When compared with population‐based studies, rates were slightly higher in children younger than 15, similar for the 15‐ to 24‐year age group, but lower for ages 25–64 years. The ethnicity‐specific odds ratios for initial unprovoked seizure, by using non‐Hispanic white as the referent, were 1.04 (0.73–1.49) for African‐American, 0.97 (0.64–1.48) for Hispanic, and 0.25 (0.08–0.84) for Asian‐American. Conclusions: The lower rate in the HMO population is presumably due to a healthy‐worker effect. The ethnicity‐specific incidence rates do not differ in this population.
Ketosis and Epilepsy: 31P Spectroscopic Imaging at 4.1 T
Authors: Pan J. W. , Bebin E. M. , Chu W. J. , Hetherington H. P. 
Published: August 2005

Summary: Purpose: To determine whether changes in the high‐energy phosphates occur with use of the ketogenic diet in patients with intractable epilepsy. Methods:
31P magnetic resonance spectroscopic imaging studies were performed at 4.1 T in seven patients with intractable epilepsy (four Lennox‐Gastaut syndrome, one absence, one primary generalized tonic‐clonic, and one partial complex) before and after institution of the ketogenic diet. Coronal 1H anatomic imaging also was performed to provide correlation to the 31P data. Results: Taking the patients as a group, the ratio of phosphocreatine (PC)/γ‐adenosine triphosphate (ATP) measured at baseline (regular diet) compared with that measured after the ketogenic diet showed a small but significant increase from 0.61 ± 0.08 to 0.69 ± 0.08 (p < 0.05). Comparing the ratio of PCr inorganic phosphorus (Pi) measured at baseline with the postketogenic diet, there was a significant increase from 2.45 ± 0.27 to 2.99 ± 0.44 (p < 0.05). Conclusions: As a group, improvement of energy metabolism occurs with use of the ketogenic diet. This is in agreement with the chronic ketosis studies performed earlier in rodents.
Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius
Authors: Walker Benjamin R. , Easton Amy , Gale Karen 
Published: August 2005

Summary: Purpose: The nucleus of the solitary tract (NTS) is a primary site at which vagal afferents terminate. Because afferent vagal nerve stimulation has been demonstrated to have anticonvulsant effects, it is likely that changes in synaptic transmission in the NTS can regulate seizure susceptibility. We tested this hypothesis by examining the influence of γ‐amino‐butyric acid (GABA) ergic and glutamatergic transmission in the NTS on seizures evoked by systemic and focal bicuculline and systemic pentylenetetrazol (PTZ) in rats. Methods: Muscimol (256 pmol), a GABAA‐receptor agonist, bicuculline methiodide (177 pmol), a GABAA‐receptor antagonist, kynurenate (634 pmol), a glutamate‐receptor antagonist, or lidocaine (100 nl; 5%), a local anesthetic, was microinjected into the mediocaudal (m)NTS. Ten minutes later, seizure activity was induced by either a focal microinfusion of bicuculline methiodide (177 pmol) into the rostral piriform cortex, systemic PTZ (50 mg/kg, i.p.), or systemic bicuculline (0.35 mg/kg, i.v.). Results: Muscimol in mNTS (but not in adjacent regions of NTS) attenuated seizures in all seizure models tested, whereas bicuculline methiodide into mNTS did not alter seizure responses. Kynurenate infusions into mNTS significantly reduced the severity of seizures evoked both systemically and focally. Anticonvulsant effects also were obtained with lidocaine application into the same region of mNTS. Unilateral injections were sufficient to afford seizure protection. Conclusions: Our results demonstrate that an increase in GABA transmission or a decrease in glutamate transmission in the rat mNTS reduces susceptibility to limbic motor seizures. This suggests that inhibition of mNTS outputs enhances seizure resistance in the forebrain and provides a potential mechanism for the seizure protection obtained with vagal stimulation.
Visual Confrontation Naming Outcome After Standard Left Anterior Temporal Lobectomy with Sparing Versus Resection of the Superior Temporal Gyrus: A Randomized Prospective Clinical Trial
Authors: Hermann Bruce , Davies Keith , Foley Kevin , Bell Brian 
Published: August 2005

Summary: Purpose: Intraoperative mapping of eloquent cortex during left (speech dominant) anterior temporal lobectomy has shown a significant proportion of patients to have sites on the anterior superior temporal gyrus at which visual confrontation naming can be disrupted by electrical stimulation. The purpose of this investigation was to conduct a randomized clinical trial to determine whether sparing versus resection of the superior temporal gyrus affected visual confrontation naming outcome after standard left anterior temporal lobectomy. Also examined was the degree to which inherent patient characteristics were associated with language outcome regardless of surgical technique. Methods: Thirty patients with intractable left temporal lobe epilepsy undergoing standard anterior temporal lobectomy were randomized in regard to whether the superior temporal gyrus was resected or spared. Patients were tested preoperatively and 6–8 months postoperatively by using two conventional tests of visual confrontation naming ability. Results: No significant differences were found between the groups in either confrontation naming or surgical outcome. Postoperative decline in nominal speech was most closely associated with later age at onset of epilepsy/absence of hippocampal sclerosis. Conclusions: It appears that specific types of localization‐related temporal lobe epilepsy are more closely associated with the risk of adverse language outcome after anterior temporal lobectomy than with the surgical variations investigated in this study.
Adding Lamotrigine to Valproate: Incidence of Rash and Other Adverse Effects
Authors: Faught Edward , Morris George , Jacobson Mercedes , French Jacqueline , Harden Cynthia , Montouris Georgia , Rosenfeld William ,   Postmarketing Antiepileptic Drug Survey (PADS) Group
Published: August 2005

Summary: Purpose: Valproate (VPA) triples the half‐life of lamotrigine (LTG), and combined use may be difficult. The adverse effect (AE) profile of this combination needs clarification. Methods: We prospectively recorded our experience in adding LTG to VPA‐containing regimens in 108 patients. Data collected included medications, seizure types and syndromes, and AEs. Patients were followed up to 27 months, until a stable dose was reached, or until LTG was discontinued. Patient management was not altered by this study. There were 60 patients with partial‐onset seizures, 30 with generalized onset, and 12 with the Lennox‐Gastaut syndrome. In 37, LTG was added to VPA monotherapy, and in 71, to VPA and other drugs. The median starting dose of LTG in our adult patients was 20.8 mg/day. Results: LTG was added successfully in 86 (80%) patients. It was discontinued in 22 (20%): seven because of rash, seven for other AEs, and nine for other reasons. Rash occurred in 14 (13%) but caused discontinuation of LTG in only seven. We found a rash rate of 14.2% and a discontinuation rate because of rash of 8.7% among 310 patients in whom LTG was added to drug regimens not including VPA. Other AEs included fatigue (12%), gastrointestinal (GI) symptoms (9%), dizziness, headache, and insomnia (3% each). Serious AEs were hallucinations (two patients), hepatic enzyme elevations (two patients), irritability (one patient), and low white blood cell count (one patient). Whether LTG was added to VPA monotherapy or polytherapy made no difference in overall AE rate. Conclusions: LTG can be added to VPA with an acceptable incidence of side effects. LTG‐induced rashes are no more common with VPA than with other drugs when LTG is added at very low initial dosages. Rashes are potentially serious and should be evaluated promptly.
The Efficacy of Valproate‐Lamotrigine Comedication in Refractory Complex Partial Seizures: Evidence for a Pharmacodynamic Interaction
Authors: Pisani F. , Oteri G. , Russo M. F. , Di Perri R. , Perucca E. , Richens A. 
Published: August 2005

Summary: Purpose: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs). Methods: After a 3‐month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add‐on treatments with VPA, LTG, or their combination, according to an open, response‐conditional, crossover design. Each period consisted of a 6‐ to 12‐week dose optimization followed by 3‐month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next. Results: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62–78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA—LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration. Conclusions: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects.
Effects of Blocking GABA Degradation on Corticotropin‐Releasing Hormone Gene Expression in Selected Brain Regions
Authors: Tran Viet , Hatalski Carolyn G. , Yan Xiao‐Xin , Baram Tallie Z. 
Published: August 2005

Summary: Purpose: The γ‐aminobutyric acid (GABA) degradation blocker γ‐vinyl‐GABA (VGB) is used clinically to treat seizures in both adult and immature individuals. The mechanism by which VGB controls developmental seizures is not fully understood. Specifically, whether the anticonvulsant properties of VGB arise only from its elevation of brain GABA levels and the resulting activation of GABA receptors, or also from associated mechanisms, remains unresolved. Corticotropin‐releasing hormone (CRH), a neuropeptide present in many brain regions involved in developmental seizures, is a known convulsant in the immature brain and has been implicated in some developmental seizures. In certain brain regions, it has been suggested that CRH synthesis and release may be regulated by GABA. Therefore we tested the hypothesis that VGB decreases CRH gene expression in the immature rat brain, consistent with the notion that VGB may decrease seizures also by reducing the levels of the convulsant molecule, CRH. Methods: VGB was administered to immature, 9‐day‐old rats in clinically relevant doses, whereas littermate controls received vehicle. Results: In situ hybridization histochemistry demonstrated a downregulation of CRH mRNA levels in the hypothalamic paraventricular nucleus but not in other limbic regions of VGB‐treated pups compared with controls. In addition, VGB‐treated pups had increased CRH peptide levels in the anterior hypothalamus, as shown by radioimmunoassay. Conclusions: These findings are consistent with a reduction of both CRH gene expression and secretion in the hypothalamus, but do not support an indirect anticonvulsant mechanism of VGB via downregulation of CRH levels in limbic structures. However, the data support a region‐specific regulation of CRH gene expression by GABA.
Long‐Term Neuropsychological Consequences of Maternal Epilepsy and Anticonvulsant Treatment During Pregnancy for School‐Age Children and Adolescents
Authors: Koch S. , Titze K. , Zimmermann R. B. , Schröder M. , Lehmkuhl U. , Rauh H. 
Published: August 2005

Summary: Purpose: Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long‐term effects of intrauterine AED exposure on neurologic and psychological functioning. Methods: Of a prospective study, “Epilepsy, pregnancy, and child development,” children could be retraced at school age and adolescence. Sixty‐seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects. Results: Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage. Conclusions: Maternal epilepsy and AED therapy during pregnancy appear to have long‐term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no‐drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors.
Interictal Epileptiform Discharges in Temporal Lobe Epilepsy Due to Hippocampal Sclerosis Versus Medial Temporal Lobe Tumors
Authors: Hamer H. M. , Najm I. , Mohamed A. , Wyllie E. 
Published: August 2005

Summary: Purpose: It remains controversial whether a specific pattern of interictal epileptiform activity exists that may help to differentiate temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) from other forms of TLE. In this study, we characterized the distribution of interictal epileptiform discharges in TLE due to HS as compared with those in patients with tumors restricted to the medial temporal lobe structures. Methods: The study included 21 adult patients with unilateral HS who remained seizure free (>1 year) after anterior temporal lobectomy with amygdalohippocampectomy. Patients with “dual pathology” were excluded. The comparison group consisted of nine patients with tumors restricted to the amygdala and hippocampus. All patients underwent video‐EEG monitoring preoperatively by using 39 scalp electrodes (including the 10–10 system over both temporal regions) and bilateral sphenoidal electrodes. Results: The HS patient group showed a significantly higher percentage of ipsilateral epileptiform discharges maximal at anterior temporal electrodes (median, 97.0%; sphenoidal electrode alone, 88.1%), as compared with the tumor group (median, 72.1%; p < 0.001; sphenoidal electrode alone, 24.8%; p < 0.001). The HS group had significantly fewer extratemporal spikes/sharp waves (median, 0.0), as compared with the tumor group (10.0%; p < 0.001). At least 90% of the interictal discharges were located in the anterior temporal region in 20 (95.2%) of 21 HS patients, but in none of the tumor patients (p < 0.001). Bilateral temporal discharges were found in nine (42.9%) of 21 patients with HS and in two (22.2%) of nine tumor patients (p = 0.42). Conclusions: We conclude that ipsilateral interictal epileptiform discharges outside the anterior temporal region are rare (<10%) in adults with intractable TLE due to unilateral HS. Frequent posterior or extratemporal sharp waves may detract from the certainty of this diagnosis in complicated cases. These restricted epileptiform discharges suggest a smaller irritative zone in HS as compared with medial tumors, or a more organized activity associated with intrinsic hippocampal disease. Bilateral epileptiform discharges were not uncommon in both groups.
The Spanish Version of the Quality‐of‐Life in Epilepsy Inventory (QOLIE‐31): Translation, Validity, and Reliability
Authors: Torres Xavier , Arroyo Santiago , Araya Susana , de Pablo Joan 
Published: August 2005

Summary: Purpose: Spanish adaptation of the Quality of Life in Epilepsy Inventory (QOLIE‐31). Methods: Internal consistency and construct validity of the Spanish translation of the QOLIE‐31 were tested in 252 patients with epilepsy. Patients also were administered the General Health Questionnaire (GHQ‐28), and the Nottingham Health Profile (NHP). Two weeks after the first test, a subgroup of randomly selected patients were readministered the QOLIE‐31 along with a new five‐option question about change in health status. Patients reporting no change in health status were included in the study of temporal stability. Sensitivity to clinical change was assessed in 31 additional patients who had successfully undergone epilepsy surgery. Results: The QOLIE‐31 was highly correlated with the GHQ‐28 (r=−0.63) and the NHP (r=−0.69), demonstrating construct validity. Cronbach's alpha coefficient was 0.92, showing the items of the QOLIE‐31 to be interdependent and homogeneous. For a 2‐week test retest, both Pearson product‐moment correlation and intraclass correlation coefficients were 0.90, indicating temporal stability. Sensitivity to clinical change was suggested by a significant mean difference between the global scores both before and after epilepsy surgery (‐21.87, p < 0.0001; 95% CI, −28.08 to −15.66). The standardized response mean of the global score was 1.67, and the effect size was 1.35, both indicating large clinical change as a result of seizure relief. Conclusions: The similarity of psychometric properties between the English and the Spanish versions of the QOLIE‐31 supports their conceptual equivalence. The questionnaire's responsiveness to clinical change suggests its utility in outcome assessment of drug trials and epilepsy surgery.
Acute Cellular Alterations in the Hippocampus After Status Epilepticus
Authors: Macdonald Robert L. , Kapur Jaideep 
Published: August 2005

Summary:The critical, fundamental mechanisms that determine the emergence of status epilepticus from a single seizure and the prolonged duration of status epilepticus are uncertain. However, several general concepts of the pathophysiology of status epilepticus have emerged: (a) the hippocampus is consistently activated during status epilepticus; (b) loss of GABA‐mediated inhibitory synaptic transmission in the hippocampus is critical for emergence of status epilepticus; and, finally (c) glutamatergic excitatory synaptic transmission is important in sustaining status epilepticus. This review focuses on the alteration of GABAergic inhibition in the hippocampus that occurs during the prolonged seizures of status epilepticus. If reduction in GABAergic inhibition leads to development of status epilepticus, enhancement of GABAergic inhibition would be expected to interrupt status epilepticus. Benzodiazepines and barbiturates are both used in the treatment of status epilepticus and both drugs enhance GABAA receptor‐mediated inhibition. However, patients often become refractory to benzodiazepines when seizures are prolonged, and barbiturates are often then used for these refractory cases of status epilepticus. Recent evidence suggests the presence of multiple GABAA receptor isoforms in the hippocampus with different sensitivity to benzodiazepines but similar sensitivity to barbiturates, thus explaining why the two drug classes might have different clinical effects. In addition, rapid functional plasticity of GABAA receptors has been demonstrated to occur during status epilepticus in rats. During status epilepticus, there was a substantial reduction of diazepam potency for termination of the seizures. The loss of sensitivity of the animals to diazepam during status epilepticus was accompanied by an alteration in the functional properties of hippocampal dentate granule cell GABAA receptors. Dentate granule cell GABAA receptor currents from rats undergoing status epilepticus had reduced sensitivity to diazepam and zinc but normal sensitivity to GABA and pentobarbital. Therefore, the prolonged seizures of status epilepticus rapidly altered the functional properties of hippocampal dentate granule cell GABAA receptors, possibly explaining why benzodiazepines and barbiturates may not be equally effective during treatment of the prolonged seizures of status epilepticus. A comprehensive understanding of the cellular and molecular events leading to the development, maintenance, and cytotoxicity of status epilepticus should permit development of more effective treatment strategies and reduction in the mortality and morbidity of status epilepticus.
Management Approaches to Prolonged Seizures and Status Epilepticus
Authors: Bleck Thomas P. 
Published: August 2005

Summary:Status epilepticus (SE) treatment should proceed on four fronts: termination of SE, prevention of recurrence, management of potential precipitating causes, and management of SE complications and underlying conditions. The intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. The Veterans Administration cooperative trial showed that when treating overt SE, first‐line treatment success rates were: lorazepam 64.9%; phenobarbital 58.2%; diazepam/phenytoin 55.8%; and phenytoin alone 43.6%. The aggregate response rate to second‐line agents for patients who did not respond to first‐line agents was 7.0%, and it was 2.3% for third‐line agents, raising the question of the efficacy of a second and third drug. The recommended treatment for generalized convulsive SE is to begin with lorazepam. As a second‐line agent, phenytoin or fosphenytoin, is still recommended if SE control is not achieved within 5 to 7 min. Fosphenytoin achieves a free phenytoin level of about 2 μ/mL in 15 min, as opposed to 25 min with phenytoin itself. Moreover, fosphenytoin is safer and, despite higher cost, it may be cost‐effective. High‐dose barbiturates, high‐dose benzodiaz‐epines, and propofol are employed for major treatment for refractory SE. Patients at this stage should undergo continuous electroencephalogram monitoring. Once SE is controlled, prevention of seizure recurrence should be individualized to each patient. The major complications of generalized convulsive SE (GCSE), rhabdomyolysis and hyperthermia, should be watched for and treated.