bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of the Novel Anticonvulsant, BIA 2‐093, with Voltage‐Gated Sodium Channels: Comparison with Carbamazepine
Authors: Bonifácio M. J. , Sheridan R. D. , Parada A. , Cunha R. A. , Patmore L. , Soares‐da‐Silva P. 
Published: March 2003

Summary:  Purpose: BIA 2‐093 [(S)‐(‐)‐10‐acetoxy‐10,11‐dihydro‐5H‐dibenz/b,f/azepine‐5‐carboxamide] is endowed with an anticonvulsant potency similar to that of carbamazepine (CBZ), but produces less cognitive and motor impairment. This study evaluated whether voltage‐gated sodium channels (VGSCs) are a primary locus for the action of BIA 2‐093.Methods: We used the whole‐cell voltage‐clamp technique in the mouse neuroblastoma cell line N1E‐115 to investigate the effects of BIA 2‐093 and CBZ on VGSCs, displacement of [3H]‐batrachotoxinin A 20‐α‐benzoate ([3H]‐BTX), and [3H]‐saxitoxin to define their relative potency to bind to rat brain sodium channels, and inhibition of uptake of 22Na by rat brain cortical synaptosomes stimulated by veratridine as a measure of sodium entry.Results: The inhibitory potencies of BIA 2‐093 and CBZ increased as the holding potential was made less negative (−100, −90, −80, and −70 mV) with median inhibitory concentration (IC50) values (in μM) of, respectively, 4,337, 618, 238, and 139 for BIA 2‐093, and 1,506, 594, 194, and 101 for CBZ. BIA 2‐093 displayed a similar potency in displacing [3H]‐BTX (IC50 values, 222 vs. 361 μM; p > 0.05) and inhibiting the uptake of 22Na (IC50 values, 36 vs. 138 μM; p > 0.05). Both drugs failed to displace [3H]‐saxitoxin in concentrations up to 300 μM.Conclusions: BIA 2‐093, like CBZ, inhibits sodium currents in a voltage‐dependent way by an interaction predominantly with the inactivated state of the channel and interacts with neurotoxin receptor site 2, but not with receptor site 1. BIA 2‐093 displayed a potency blocking VGSCs similar to that of CBZ.
Concomitant Treatment with Topiramate and Ketogenic Diet in Pediatric Epilepsy
Authors: Takeoka Masanori , Riviello James J. , Pfeifer Heidi , Thiele Elizabeth A. 
Published: March 2003

Summary:  Purpose: Topiramate (TPM) is widely used as add‐on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD.Methods: Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control.Results: Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained on cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis.Conclusions: Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels should be monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic.
Topiramate Selectively Decreases Intracortical Excitability in Human Motor Cortex
Authors: Reis Janine , Tergau Frithjof , Hamer Hajo M. , Müller Hans‐Helge , Knake Susanne , Fritsch Brita , Oertel Wolfgang H. , Rosenow Felix 
Published: March 2003

Summary:  Purpose: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium‐channel blocker, as γ‐aminobutyric acid type A (GABAA)‐receptor agonist and as non–N‐methyl‐D‐aspartate (NMDA)‐glutamate receptor antagonist.Methods: With transcranial magnetic stimulation (TMS), we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability. In a double‐blind, placebo‐controlled, crossover study design, we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical silent period (CSP), and on intracortical inhibition (ICI) and intracortical facilitation (ICF) in 20 healthy subjects.Results: A significant dose‐dependent increase of ICI was noticed after 200 mg TPM as compared with placebo at short interstimulus intervals of 2 to 4 ms. TPM had no effect on motor thresholds or the CSP.Conclusions: We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion‐channel blockade or GABAB‐receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.
Selective Middle Cerebral Artery Wada Tests as a Part of Presurgical Evaluation in Patients with Drug‐resistant Epilepsies
Authors: Urbach Horst , Von Oertzen Joachim , Klemm Edzard , Koenig Roy , Linke Detlef B. , Kurthen Martin , Schramm Johannes , Elger Christian E. 
Published: March 2003

Summary:  Purpose: To analyze the role of selective middle cerebral artery (MCA) Wada tests in the presurgical workup of patients with drug‐resistant focal epilepsies.Methods: Twenty MCA Wada test procedures were performed to identify eloquent cortex (a) in nine patients with hemispheric lesions involving the motor cortex (connatal MCA infarct, n = 5; unilateral cortical dysplasia, n = 3; Rasmussen encephalitis, n = 1), (b) five patients with circumscribed neoplastic or nonneoplastic lesions adjacent to the motor cortex or classic language areas, and (c) for purely electrophysiologic reasons, in two patients with electrical status epilepticus in sleep (ESES). Sodium amobarbital and [99mTc]‐HMPAO were simultaneously injected via a microcatheter into the distal M1 segment (n = 7), the inferior MCA trunk (n = 3), or into MCA branches (n = 10).Results: Co‐registered single‐photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI;n = 18) showed that sodium amobarbital did not reach the target area in three procedures. Temporary neurologic deficits occurred in 12 procedures. Eleven patients were operated on with the following surgical approaches: functional hemispherectomy, n = 3; partial or extended lesionectomy, n = 4; anterior temporal lobectomy, n = 1; and multiple subpial transsections, n = 3. Seizure freedom (Engel class I) was achieved in five patients.Conclusions: Selective MCA Wada tests can contribute to risk assessment concerning postsurgical motor deficits before functional hemispherectomy. Other indications are less clear: The identification of language areas is targeted primarily by electrical‐stimulation mapping after subdural grid implantations, and selective MCA Wada tests in ESES patients yet have to be validated in larger patient groups.
FDG‐PET Images Quantified by Probabilistic Atlas of Brain and Surgical Prognosis of Temporal Lobe Epilepsy
Authors: Lee Sang Kun , Lee Dong Soo , Yeo Jeong Seok , Lee Jae Sung , Kim Yu Kyeong , Jang Myoung Jin , Kim Kwang‐Ki , Kim Seok‐Ki , Oh Jong‐Bai , Chung Chun‐Kee 
Published: March 2003

Summary:  Purpose: This study evaluated the relation between hypometabolism, diagnosed by fluorodeoxyglucose positron emission tomography (FDG‐PET), and the surgical outcome of a large and homogeneous series of cases of mesial temporal lobe epilepsy (mTLE), by using a probabilistic atlas of the human brain (statistical probabilistic anatomical maps: SPAM).Methods: Ninety‐five surgically proven intractable mTLE patients and 22 age‐matched controls were spatially normalized to the average brain PET template of international consortium of brain mapping (ICBM). The diagnosis of mTLE was confirmed by the presence of hippocampal sclerosis on magnetic resonance imaging (MRI) and video‐EEG monitoring. Counts from normalized PET images were multiplied by the probability from 98 volumes of interest (VOIs) of SPAM. Asymmetric indexes (AIs) reflecting the severity of hypometabolism were calculated by counts of selected 12 VOIs from SPAM images in both temporal lobes. Extent of hypometabolism was determined by the number of voxels showing decreased metabolism in each VOI segmented by SPAM.Results: Of the 95 patients studied, 76 (80%) were seizure free, and 19 (20%) had postoperative seizures for the ≥2‐year follow‐up period. No significant association between the severity of hypometabolism in each VOI of the temporal lobe and surgical outcome was identified (p > 0.05). The number of voxels showing decreased hypometabolism was not significantly different between the good‐ and poor‐outcome groups (p > 0.05).Conclusions: Our results demonstrated that focal severity and extent of hypometabolism quantified by a probabilistic atlas of brain were not related to the surgical outcome in mTLE patients who had hippocampal sclerosis on MRI. We should develop a more localized and specified anatomic map for mTLE for further results.
Agranulocytosis Associated with Lamotrigine in a Patient with Low‐grade Glioma
Authors: Fadul Camilo E. , Meyer Louise P. , Jobst Barbara C. , Cornell Cornelius J. , Lewis Lionel D. 
Published: March 2003

Summary:  Purpose: To report agranulocytosis associated with lamotrigine (LTG) in a patient with a brain tumor.Methods: A 59‐year‐old woman with a low‐grade glioma and difficult‐to‐control partial seizures developed agranulocytosis between 9 and 14 weeks after starting LTG. The patient underwent chemotherapy 2 years previously.Results: After stopping LTG, the agranulocytosis persisted for 9 days despite 7 days of granulocyte–colony‐stimulating factor (G‐CSF), and ultimately resolved.Conclusions: In this case, the use of LTG was associated with the development of agranulocytosis, and it is likely that this association was causative.
Increased Expression of the Neuronal Glutamate Transporter (EAAT3/EAAC1) in Hippocampal and Neocortical Epilepsy
Authors: Crino Peter B. , Jin Hong , Shumate Melissa D. , Robinson Michael B. , Coulter Douglas A. , Brooks‐Kayal Amy R. 
Published: March 2003

Summary: Purpose:To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy.Methods:The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine‐induced temporal lobe epilepsy (TLE) and age‐matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis.Results:The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with nondysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT‐1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue.Conclusions:Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types.
Depression in Intractable Partial Epilepsy Varies by Laterality of Focus and Surgery
Authors: Quigg Mark , Broshek Donna K. , Heidal‐Schiltz Susan , Maedgen Jennifer W. , Bertram Edward H. 
Published: March 2003

Summary:  Purpose: Depression sometimes occurs after surgical treatment for medically intractable partial epilepsy. The risk of pre‐ and postsurgical depression may vary by laterality of seizure focus. We reviewed the pre‐ and postsurgical psychological assessments and clinical courses of patients to identify those at highest risk for postsurgical mood disorders.Methods: Depression status was assessed in a consecutive series of epilepsy patients before and 1 year after epilepsy surgery with the use of Scale 2 of the MMPI‐2 and a clinical depression index (CDI) scoring the occurrence of depressive symptoms, psychiatric referral, or attempted/completed suicide. Outcome at 1 year was modeled by regression techniques as functions of preoperative mood measurements, side of epilepsy surgery, and preoperative verbal intelligence.Results: The CDI and Scale 2 MMPI‐2 correlated significantly (r = 0.341; p ≤ 0.01). Left (n = 54 subjects) and right (n = 53) surgery groups did not differ by sex, seizure outcome, age, education, age at first seizure, duration of epilepsy, or intellect. Higher presurgical depressive morbidity (p = 0.0037) and right‐sided surgery (p = 0.0003) predicted higher postoperative CDI. Higher preoperative Scale 2 scores, indicating worse depressive traits, predicted worse postoperative Scale 2 scores (p < 0.0001). Although side of surgery did not predict Scale 2 scores, Scale 2 scores of patients with preoperative right‐sided foci tended to have worse postsurgical Scale 2 scores (p = 0.08). Findings for the temporal lobectomy subgroup (n = 90) were similar to those of the overall sample.Conclusions: Patients undergoing right hemispheric epilepsy surgery, especially those with high presurgical depression–related morbidity, may be particularly susceptible to clinical depression. Our findings support other studies that show an interhemispheric modulation of depressive traits and symptoms.
A Multicenter Study on the Prevalence of Psychiatric Disorders among New Referrals for Epilepsy in Japan
Authors: Matsuura Masato , Oana Yasunori , Kato Masaaki , Kawana Akinori , Kan Rumiko , Kubota Humio , Nakano Takashi , Hara Tsunekatsu , Horikawa Naoshi 
Published: March 2003

Summary:  Purpose: To investigate the prevalence rate and risk factors of psychiatric disorders among new referrals for epilepsy, a multicenter study was conducted by using the International League Against Epilepsy (ILAE) criteria for epilepsy and the ICD‐10 criteria for psychiatric disorders.Methods: From April 2000 to March 2001, 398 patients with epilepsy, who were referred to nine neuropsychiatric outpatient clinics specialized for epilepsy in the Tokyo metropolitan area, were evaluated by using a newly developed five‐axis classification scheme.Results: Forty‐two percent of the subjects showed a psychiatric disorder. Twenty‐four percent of the total showed psychiatric disorders, including neurotic disorders in 8%, psychotic disorders in 7%, and affective disorders in 1%. In addition, 23% of the total showed mental retardation, and 18% showed personality disorders. A logistic regression analysis revealed that the three risk factors for a psychiatric disorder were mental retardation, temporal lobe epilepsy (as opposed to other subtypes), and a high seizure frequency.Conclusions: The presence of mental retardation was the primary risk factor for developing a psychiatric disorder, especially a schizophrenia‐spectrum disorder. The type of epilepsy alone is not a strong predictor of psychiatric illness, and intractable temporal lobe epilepsy with a high seizure frequency is accountable for the link between the epilepsy and the psychiatric illness.
Interictal Epileptic Spiking during Sleep and Wakefulness in Mesial Temporal Lobe Epilepsy: A Comparative Study of Scalp and Foramen Ovale Electrodes
Authors: Clemens Zsófia , Janszky József , Szűcs Anna , Békésy Mariann , Clemens Béla , Halász Péter 
Published: March 2003

Summary:  Purpose: To assess distribution of temporal lobe spikes across different states of sleep and wakefulness in simultaneous scalp and foramen ovale (Fo) recordings.Methods: The study included 12 patients with mesial temporal lobe epilepsy (MTLE). As part of their presurgical evaluation, patients underwent long‐term video‐EEG monitoring with combined scalp and foramen ovale electrodes (FoEs). In addition to traditional sleep scoring, waking was subdivided into eyes‐opened and eyes‐closed states, and rapid‐eye‐movement (REM) sleep was divided into phasic and tonic states. Spike counts were carried out visually for scalp and FoEs, and spiking rates were determined for each state. A ratio between FoE and scalp spiking rates also was calculated for each state.Results: Scalp spiking showed a significant increase during NREM3,4, whereas FoE spiking increased during NREM2. The scalp/FoE ratio significantly increased during NREM3,4. A significant difference in spiking rate also was found between phasic and tonic REM states as well as between waking with eyes opened and closed in FoE recordings.Conclusions: Our data provide evidence of a discrepancy in spike distribution across different states of sleep and waking monitored by scalp and FoE recordings. We suggest that these discrepancies may reflect differences in archicortical and neocortical spike synchronization.
Treatment of Phenytoin Toxicity by the Molecular Adsorbents Recirculating System (MARS)
Authors: Sen Sambit , Ratnaraj Neville , Davies Nathan A. , Mookerjee Rajeshwar P. , Cooper Christopher E. , Patsalos Philip N. , Williams Roger , Jalan Rajiv 
Published: March 2003

Summary:  Purpose: Toxicity is common in patients of epilepsy treated with phenytoin (PHT), requiring careful drug level monitoring and supportive care. Specific treatment options are limited, although charcoal haemofiltration has been used previously. We attempted to demonstrate that severe PHT toxicity can be treated successfully with the Molecular Adsorbents Recirculating System (MARS). The mechanism of drug removal by the system also was studied.Methods: A 45‐year‐old patient of status epilepticus with acute renal failure and severe PHT toxicity, associated with cardiac arrhythmias, hepatotoxicity, and altered sensorium, was treated with the MARS, a blood‐purification system based on albumin dialysis, and including a charcoal filter, for 11.5 h. Serum PHT levels and blood levels of oxygen‐based free radicals (by electron paramagnetic resonance spectroscopy) were measured before and after treatment.Results: Serum total and free PHT levels declined sharply (32 to 11 μM and 9.8 to 2.0 μM, respectively), with clinical improvement and a 65% reduction in measured oxidative stress. The mechanism of drug removal, deduced by measuring PHT in the dialysate collected from different segments of the MARS circuit, was by clearance from blood into the albumin dialysate, and ultimately removal by the charcoal filter.Conclusions: The observed removal of PHT by MARS, along with the clinical improvement of the patient and reduction of the associated oxidative stress after treatment, indicates that MARS offers a promising option in PHT toxicity.
Anterior Thalamic Mediation of Experimental Seizures: Selective EEG Spectral Coherence
Authors: Mirski Marek A. , Tsai Yien Che , Rossell Lisa Ann , Thakor Nitish V. , Sherman David L. 
Published: March 2003

Summary:  Purpose: Physiological evidence has shown that the anterior thalamus (AN) and its associated efferents/afferents constitute an important propagation pathway for pentylenetetrazol (PTZ)‐mediated generalized seizures in rodents. Previous work demonstrated metabolic, physical, chemical, and electrical stimulation data supporting a role for AN in the expression of PTZ seizures. We now extend these observations through examination of neuroelectric signal indicators during seizure epochs. We show that the EEG recorded from AN is highly coherent with surface cortical (CTX) EEG during the immediate preconvulsant period and during the ictal stateough.Methods: Awake rats were continuously infused with PTZ until clonic seizures were recorded by using both subcortical AN, posterior thalamus (PT), or hippocampal (HPC) bipolar electrodes and cortical EEG. Through the signal‐analysis techniques of ordinary and partial coherence, it was possible to focus selectively on signal correlations between AN and CTX (AN/CTX) by removing the effects of unaffiliated regions such as PT and HPC.Results: Coherence of PT/CTX was observed to be modest, and partial coherence of PT/CTX with the effects of AN/CTX removed did not improve the signal coherence of PT/CTX (PT/CTX‐AN). In contrast, AN/CTX coherence was observed to be high, with undiminished correlation when PT/CTX influence was removed (AN/CTX‐PT). The most robust band of AN/CTX coherence was centered around the spike–wave clonic frequency of 1–3 Hz. Partial multiple coherence‐analysis techniques were used to remove the possible signal contributions from hippocampus in addition to PT. The AN/CTX coherence remained fully preserved in the low‐frequency bands.Conclusions: These data provide electrophysiologic evidence supporting the special role of the anterior thalamus in the propagation of seizure activity between subcortex and cortex.
EEG in Children with Early‐onset Benign Occipital Seizure Susceptibility Syndrome: Panayiotopoulos Syndrome
Authors: Ohtsu Mayu , Oguni Hirokazu , Hayashi Kitami , Funatsuka Makoto , Imai Kaoru , Osawa Makiko 
Published: March 2003

Summary: Purpose:We analyzed sequential changes in the localization of EEG foci along with age to identify a specific EEG pattern, and the relation between the clinical manifestations and the EEG pattern in patients with Panayiotopoulos syndrome (PS).Methods:The subjects were 76 children, who had been followed up >2 years with repeated EEG examinations at 6‐month intervals. Analysis of EEG findings included the determination of localization of spike foci, as a function of age, by using cross‐sectional data, and the identification of subgroups with homogeneous EEG patterns. Then we compared certain clinical features among these subgroups.Results:In the cross‐sectional EEG study, the occipital EEG spike focus was most frequently seen between ages 2 and 5 years. Independent and synchronous frontopolar and occipital spikes (Fp‐O spikes) and centroparietotemporal (CPT) EEG spike foci had increased incidences between ages 4 and 7 years, and between ages 6 and 10 years, respectively. We subclassified the 76 patients into the following five subgroups based on the evolutional changes in epileptic EEG foci, which frequently showed shifting, multiplications, and generalization: (a) persistent occipital focus group (O group), (b) Fp‐O spikes group (Fp‐O pattern group), (c) generalized EEG pattern group, (d) CPT foci group (CPT group), and (e) no epileptic EEG focus group. The Fp‐O group showed the latest age at onset of epilepsy. The generalized EEG pattern group had the highest frequency of seizures as well as recurrences of status epilepticus (SE), as well as the longest active seizure period among the five groups.Conclusions:These results indicated that the EEG foci in most of patients with PS are frequently shifting location, multiplying, and propagating diffusely with age, rather than persistently localizing in the occipital region. In addition, the EEG patterns showed a certain trend and roughly corresponded to certain clinical characteristics. However, the prognosis of the seizures appeared to be favorable regardless of the EEG pattern.