bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution and Initiation of Seizure Activity in a Rat Brain with Subcortical Band Heterotopia
Authors: Chen Zong‐Fu , Schottler Frank , Bertram Edward , Gall Christine M. , Anzivino Matthew J. , Lee Kevin S. 
Published: August 2005

Summary: Purpose: Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies. To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure‐prone mutant rat (tish) exhibiting subcortical band heterotopia. Methods: Depth electrode recordings and postmortem assessment of regional c‐fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo. Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4‐aminopyridine). Results: Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex. Spontaneous seizures induce c‐fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions. The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices. Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex. Conclusions: These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat. Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons. The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex.
Estradiol Facilitates Kainic Acid—Induced, but not Flurothyl‐Induced, Behavioral Seizure Activity in Adult Female Rats
Authors: Woolley Catherine S. 
Published: August 2005

Summary: Purpose: This study was designed to determine whether previously demonstrated increases in hippocampal axospinous synapse density and NMDA receptor function induced by estradiol are paralleled by increased susceptibility to limbic (kainic acid induced) or generalized (flurothyl induced) behavioral seizures. Methods: Kainic acid was injected systemically to ovariectomized adult female rats treated with either estradiol or oil vehicle. The latencies to each of five stages of seizure‐related behaviors (staring, wet‐dog shakes, head waving and chewing, forelimb clonus, rearing, and falling) were recorded for each animal. Flurothyl was administered by inhalation to ovariectomized adult female rats treated with estradiol alone, estradiol followed by short‐term progesterone, or oil vehicle. The latencies to each of three stages of seizure‐related behaviors (first myoclonic jerk, forelimb clonus, wild running and bouncing) were recorded for each animal. Results: Estradiol treatment decreased the latency to seizure‐related behaviors induced by kainic acid, but neither estradiol alone nor estradiol followed by progesterone had any effect on flurothyl‐induced seizure‐related behaviors. Conclusions: The same estradiol treatment paradigm known to induce structural and functional changes in the excitatory circuitry of the hippocampus facilitates the progression of kainic acid‐induced seizures, which are known to involve the hippocampus, but has no effect on flurothyl‐induced seizures. The lack of an effect of estradiol alone or estradiol followed by progesterone on flurothyl‐induced seizures indicates that estradiol's effects on seizure susceptibility do not result from increased neuronal excitability throughout the brain, but rather involve action within the limbic system. The data suggest that structural and functional changes in hippocampal circuitry induced by estradiol may contribute to increased susceptibility to limbic seizure activity.
Epilepsy, Vagal Nerve Stimulation by the NCP System, All‐Cause Mortality, and Sudden, Unexpected, Unexplained Death
Authors: Annegers J. F. , Coan Sharon P. , Hauser W. A. , Leestma J. 
Published: August 2005

Summary: Purpose: This report concerns the 2‐year extension of the study of mortality and sudden, unexpected, unexplained death in epilepsy (SUDEP) in the cohort of patients receiving vagal nerve stimulation by the NCP System for the treatment of epilepsy. Methods: A cohort of 1,819 individuals was followed 3,176.3 person‐years from implantation. The 25 deaths that occurred during NCP System activation were reviewed for SUDEP by a panel. Results: The mortality rates were lower [standardized mortality ratio (SMR = 3.6)] with the extended follow‐up compared to the previous finding (SMR = 5.3). The SUDEP rates (4.1 vs. 4.5 per 1,000 person‐years) were similar to those in the previous study of this cohort. When the vagal nerve stimulation experience is stratified by duration of use, the rate of SUDEP was 5.5 per 1,000 over the first 2 years, but only 1.7 per 1,000 thereafter. Conclusions: The mortality and SUDEP rates are similar to those reported from clinical trials of new drugs and cohorts of severe epilepsy. The lower SUDEP rates after 2 years of follow‐up are intriguing, but require further investigation.
Early Recognition of Benign Partial Epilepsy in Infancy
Authors: Okumura Akihisa , Hayakawa Fumio , Kato Toru , Kuno Kuniyoshi , Negoro Tamiko , Watanabe Kazuyoshi 
Published: August 2005

Summary: Purpose: The aim of this study is to determine how precisely we can recognize the outcome in infants with epilepsy beginning in the first year of life. Methods: We performed a prospective 5‐year follow‐up study on 63 patients who developed epilepsy in the first year of life. We first judged that patients met the criteria of “possible benign partial epilepsy in infancy (BPEI)” on enrollment in this study. At 2 years of age, we reevaluated the seizure and developmental outcome in the patients who were diagnosed as having “possible BPEI.” We finally judged that patients met the criteria of “definite BPEI” at age 5 years. “Possible BPEI” was defined as epilepsy meeting all the following conditions: (a) complex partial seizures and/or secondarily generalized seizures; (b) normal psychomotor development and neurologic findings before onset; (c) normal interictal electroencephalograms; (d) normal cranial computed tomography (CT) and magnetic resonance imaging (MRI) findings; and (e) no seizures during the first 4 weeks of life. “Definite BPEI” was defined as epilepsy meeting all the following criteria in addition to those of “possible BPEI”: (a) normal psychomotor development beyond age 5 years, and (b) no seizures beyond age 2 years. Results: Thirty‐two of the 63 patients met the inclusion criteria completely and were included in the “possible BPEI” group. Twenty‐five of the 32 patients completed the 5‐year follow‐up. At age 2 years, four patients were excluded from the “possible BPEI” group because of seizure recurrence and/or delayed development. By age 5 years, one had a recurrence of seizures, and another exhibited mildly delayed psychomotor development. We finally diagnosed 19 patients as having “definite BPEI.”“Definite BPEI” accounted for 76% of the patients diagnosed as having “possible BPEI” at the first presentation and 90% of those who met the conditions on reevaluation at age 2 years. Conclusions: Recognition of BPEI is possible, to some extent, at the first presentation, and reevaluation at age 2 years is useful for a more precise diagnosis.
Referral Characteristics of Primary Care Physicians for Seizure Patients
Authors: Moore J. Layne , McAuley James W. , Mott David , Reeves Andrew L. , Bussa Barbara 
Published: August 2005

Summary: Purpose: To investigate primary care physicians' behavior with respect to referral patterns, antiepileptic drug (AED) initiation, and level of comfort in managing seizure patients. Methods: A cross‐sectional descriptive study design was used for collecting and analyzing data. A 20‐item survey was developed and mailed to 8,195 primary care physicians including family practitioners, internal medicine physicians, and obstetrics–gynecologists throughout the state of Ohio; 504 primary care physicians that interact regularly with epilepsy patients responded to the survey. Results: Two patterns of referral emerged. Data showed that the majority (n = 382) of physicians refer 50% of their patients, but a minority of physicians (n = 122) refer <50% of their patients. Differences between the two groups existed in three of the four research questions asked: who initiates AED therapy, comfort level, and percentage of patients referred to a neurologist. Influence of managed care on decision making was not different between the two groups. Conclusions: A minority of primary care physicians rate themselves very comfortable with seizure patients. These same physicians refer a minority of their patients to a neurologist. As a whole, however, primary care physicians refer a majority of their seizure patients to a neurologist. Neurologists evaluate most seizure patients because most primary care physicians claim not to be extremely comfortable with evaluation and treatment of seizures. We conclude that neurologists play an essential role in the treatment of most seizure patients.
Validation of a New Quality of Life Measure for Children with Epilepsy
Authors: Sabaz Mark , Cairns David R. , Lawson John A. , Nheu Natalina , Bleasel Andrew F. , Bye Ann M.E. 
Published: August 2005

Summary: Purpose: There is no adequate measure of health‐related quality of life (HRQOL) specifically for children with epilepsy. The aim of this study was to develop an epilepsy‐specific HRQOL questionnaire for children, covering five domains: physical function, emotional well‐being, cognitive function, social function, and behavior. Second, we aimed to demonstrate the instrument's reliability and validity, and its sensitivity to differences in epilepsy severity. Methods: The subjects were guardians of children with refractory epilepsy, whose syndrome had been defined by using video‐EEG monitoring. Each family completed the developed epilepsy‐specific HRQOL scale for children and two standard, generic measures of HRQOL. Results: The results indicated that each of the scales of the questionnaire had good internal consistency reliability. Furthermore, each scale correlated more highly with theoretically similar scales on established, generic health measures than with theoretically dissimilar scales (construct validity). The sensitivity of the questionnaire to differences in epilepsy severity also was demonstrated. As seizure severity increased, HRQOL subscale scores decreased, independent of age, gender, age of seizure onset, and IQ. Further, there was a negative relation between the number of antiepileptic medications taken and measures of memory and language performance, which was independent of age, gender, age of seizure onset, IQ, and seizure severity. Conclusions: This study demonstrated that the developed HRQOL instrument is a reliable and valid measure and is sensitive to differences in epilepsy. These results indicate that this new instrument may be a viable medical or surgical outcome measure for children with epilepsy.
Intractable Seizures of Frontal Lobe Origin: Clinical Characteristics, Localizing Signs, and Results of Surgery
Authors: Jobst B. C. , Siegel A. M. , Thadani V. M. , Roberts D. W. , Rhodes H. C. , Williamson P. D. 
Published: August 2005

Summary: Purpose: We analyzed the clinical characteristics of seizures of frontal lobe (FL) origin with particular emphasis on establishing different categories and determining if these categories had any localizing or lateralizing value. In addition, results of surgery are reported. Methods: Seizure characteristics were established by historical review and electroencephalographic/videotape analysis of 449 seizures in 26 adult patients with refractory seizures of FL origin. Results: No outstanding risk factor was identified for seizures of FL origin. Seizures were frequent (7.1 per week), brief (mean duration, 48.3 seconds), and had a nocturnal preponderance in 58% of the patients. Status epilepticus was reported in 54%, and generalized convulsions as a prominent seizure type were reported in 26% of patients. The most common reported aura was a nonspecific sensation, often localized to the head (35%). Early forced head and eye deviation was not a consistent lateralizing sign, whereas late head and eye deviation always occurred contralateral to the site of seizure origin. Early asymmetric tonic posturing occurred consistently contralateral to the side of seizure origin. Clinical seizure patterns did not consistently localize to specific regions of the frontal lobe, although there were some noticeable trends: focal clonic seizures were associated with seizure origin in the frontal convexity; tonic seizures were most often associated with origin in the supplementary motor area but also occurred with origin in other parts of the frontal lobe; seizures resembling typical temporal lobe seizures with oroalimentary automatisms were observed with seizure origin in the orbitofrontal region; and seizures with hyperactive, frenetic automatisms were not associated with any specific region within the frontal lobes. Eighty percent of patients had favorable seizure outcome after surgery (class I/II). Conclusion: Although certain clinical features are characteristic for seizures of frontal lobe origin and some have lateralizing value, they do not localize to specific areas within the FL. After careful presurgical evaluation, both lesional and non‐lesional patients benefit from epilepsy surgery.
A Double‐Blind, Placebo‐Controlled Study of Topiramate in Adult Patients with Refractory Partial Epilepsy
Authors: Yen Der‐Jen , Yu Hsiang‐Yu , Guo Yuh‐Cherng , Chen Chien , Yiu Chun‐Hing , Su Ming‐Shung 
Published: August 2005

Summary: Purpose: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double‐blind, placebo‐controlled study. Methods: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8‐week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placcbo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial. Results: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a 50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group. Conclusions: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.
A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures
Authors: Aldenkamp A. P. , Baker G. , Mulder O. G. , Chadwick D. , Cooper P. , Doelman J. , Duncan R. , Gassmann‐Mayer C. , de Haan G. J. , Hughson C. , Hulsman J. , Overweg J. , Pledger G. , Rentmeester T. W. , Riaz H. , Wroe S. 
Published: August 2005

Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil‐ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer‐blinded, parallel‐group clinical trial with VPA or TPM given as first‐line add‐on therapy to steady‐state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25‐mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline‐to‐end point comparisons, one test measuring short‐term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline‐to‐titration comparisons also show one statistically significant difference, again for a test measuring short‐term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).
Assessment of Ganaxolone's Anticonvulsant Activity Using a Randomized, Double‐Blind, Presurgical Trial Design
Authors: Laxer Kenneth , Blum David , Abou‐Khalil Basil W. , Morrell Martha J. , Lee David A. , Data Joann L. , Monaghan Edward P. ,   the Ganaxolone Presurgical Study Group
Published: August 2005

Summary: Purpose: A double‐blind, randomized, placebo‐controlled clinical trial to examine the safety, tolerability, and antiepileptic activity of ganaxolone in patients after withdrawal from other antiepileptic drugs during presurgical evaluations was performed. Methods: Fifty‐two eligible patients were withdrawn from antiepileptic drugs and randomized to receive ganaxolone (24 patients) or placebo (28 patients) for up to 8 days. Ganaxolone was administered at a dose of 1500 mg/d on day 1 and 1875 mg/d on days 2 to 8. Dosing occurred three times per day: immediately after breakfast, lunch, and dinner. Results: The primary measure of antiepileptic activity was duration of treatment before withdrawal from the trial. Kaplan‐Meier curves depicted a clear separation between treatment groups, with 50% of the ganaxolone‐treated patients completing the entire study, compared with 25% of patients treated with placebo. Intent‐to‐treat survival analyses revealed a trend toward efficacy with ganaxolone (p = 0.0795, log rank test). Covariate analyses revealed a significant treatment effect on survival time in men (p = 0.03). Post‐hoc χ2 probe analyses focusing on patients who completed the entire study revealed a significant difference (p = 0.04) between treatment groups. The tolerability of ganaxolone was similar to that of placebo, with adverse events being reported by 79% of patients in the ganaxolone group and 68% of patients in the placebo group. Conclusions: Ganaxolone monotherapy was well tolerated for the duration of this clinical trial, and the results provide preliminary evidence that ganaxolone does have antiepileptic activity.
Lateral Asymmetry in Activation of Hypothalamic Neurons with Unilateral Amygdaloid Seizures
Authors: Silveira D. C. , Klein P. , Ransil B. J. , Liu Z. , Hori A. , Holmes G. L. , de LaCalle S. , Elmquist J. , Herzog A. G. 
Published: August 2005

Summary: Purpose: Reproductive disorders are unusually frequent among women with temporal lobe seizures. The particular type of disorder may be related to the laterality and focality of epileptiform discharges. Here we examined whether unilateral amygdaloid seizures activate hypothalamic neurons involved in reproductive function and reproductive endocrine secretion in female rats and whether such activation shows lateral asymmetry. Methods: Numbers of Fos‐immunoreactive (Fos‐ir) neurons in various hypothalamic regions were compared for three groups of animals: (a) unilateral amygdala‐kindled, (b) implanted but unstimulated, and (c) unimplanted. Results: Fos‐ir neurons showed strong ipsilateral occurrence in the medial preoptic, ventrolateral part of the ventromedial, and ventral premammillary nuclei, sexually dimorphic regions involved in reproductive endocrine regulation. No significant lateral asymmetry was observed for other investigated hypothalamic regions. Conclusions: Unilateral amygdaloid seizures activate hypothalamic neurons that regulate reproductive endocrine secretion in a laterally asymmetric fashion. This may explain the clinical association of different reproductive endocrine disorders with left and right temporal epileptiform discharges.