bluuebunny/crossref_metadata_2025 huggingface dataset:
Ictal EEG and Single Photon Emission Computed Tomography in a Patient with Cortical Dysplasia Presenting with Atonic Seizures
Authors: Aihara Masao , Hatakeyama Kazuo , Koizumi Kiyoshi , Nakazawa Shinpei
Published: August 2005

Summary: Purpose: Ictal studies of atonic seizures in children with epilepsy are rare. To clarify the neurophysiologic mechanism of such seizures, we describe a cluster of atonic seizures in a 6‐year‐old girl with cortical dysplasia.

Methods: Ictal activity was recorded as slow‐wave bursts beginning over the right frontocentral regions, where the cortical dysplasia was detected by magnetic resonance imaging (MRI), and propagating to the left hemisphere.

Results: The polygraphic recording demonstrated that the atonia indicated by the sudden interruption of elecromyogram (EMG) discharges corresponded to the bilaterally synchronous spike‐and‐wave complexes. An ictal single photon emission computed tomography (SPECT) study with 99mTc hexamethyl propylene amine oxime ([99mTc]HMPAO) simultaneously performed during EEG recording showed marked bilateral mesial frontal and right frontoparietal hyperperfusion.

Conclusions: Our findings suggest that the neurophysiological mechanism of the atonic seizures may be produced by a strong inhibition in the bilateral motor cortexes. Ictal SPECT is valuable in demonstrating the pathophysiology of both atonic seizures and secondary bilaterally synchronous spike‐and‐wave complexes in the EEG.
Carbamazepine Toxicity with Lamotrigine: Pharmacokinetic or Pharmacodynamic Interaction?
Authors: Besag F. M. C. , Berry D. J. , Pool F. , Newbery J‐J. E. , Subel B.
Published: August 2005

Summary: Purpose: To determine whether the toxicity that occurs in some patients when lamotrigine (LTG) is added to carbamazepine (CBZ) is the result of either a pharmacokinetic or a pharmacokinetic or a pharmcodynamic interaction.

Methods: Escalating LTG doses were added to ongoing CBZ treatmcnt in 47 patients. All patients had blood samples collected for drug concentration measurement, including the epoxide metabolite of CBZ, before starting LTG treatment and after stabilising at each dose escalation. Patients also were examined for signs of toxicity.

Results: After LTG was introduced, nine patients demonstrated clinical signs of CNS toxicity, mainly diplopia and diziness. There was no significant (p = 0.05) change in the serum concentrations of either CBZ or its epoxide metabolite when LTG was added either to the group as a whole or to the nine patients who experienced adverse CNS effects. LTG serum concentrations also were below the level at which the common signs of LTG toxicity, such as nausea, vomiting, or unsteadiness, are more likely to occur. In seven of the nine patients who exhibited CNS toxicity. CBZ serum concentrations were >8 mg/L on LTG introduction.

Conclusions: Toxicity is more likely to occur when LTG is added to CBZ if the initial CBZ level is high. typically >8 mg/L. This appears to be the result of a pharmacodynamic interaction. A reduction of CBZ dose usually resolves the toxicity, allowing the LTG dose to be escalated to maximal effect. It is not usually necessary to stop either drug.
Selective Amobarbital Test for the Determination of Language Function in Patients with Epilepsy with Frontal and Posterior Temporal Brain Lesions
Authors: Hajek Marketa , Valavanis Anton , Yonekawa TYasuhiro , Schiess Regula , Buck Alfred , Wieser Heinz Gregor
Published: August 2005

Summary: Purpose: Selective amobarbital tests with selective temporary inactivation of the left frontal operculum and/or the left parietotemporal cortex were performed in 5 patients with left‐hemispheric epileptogenic lesions in or adjacent to classical Broca's and/or Wemicke's aréa. The aim was to assess language functions in these brain regions before surgery, to tailor the surgery according to the individual functional importance of these brain regions, and to predict postoperative outcome.

Methods: Amobarbital was injected by transfemoral selective catheterization of the arteries supplying the target areas. Along with neuropsychological and neurological testing during the amobarbital procedure, EEG recordings were performed in all patients, and [199mTc]HMPAO‐single photon emission computed tomography (SPECT) in 2 patients.

Results: After the amobarbital injection into the left frontal opercular region, there was no recognizable language dysfunction in 3 patients. In these 3 patients, the lesions in or adjacent to the frontal operculum were completely resected without postoperative language impairment. In the remaining 2 patients, temporary language impairment after the amobarbital injection into the left frontoopercular and Wemicke's region, respectively, suggested language functions in these areas. Surgery was restricted to the left mesiotemporal lobe in 1 patient. In the other patient, the tumor infiltrating the frontal operculum was restrictively resected. Postoperatively, the fist patient had no language impairment, but the latter had transient global aphasia, from which she recovered.

Conclusions: Selective temporary amobarbital inactivation of brain regions that may be associated with language has clearly indicated the presence or absence of language functions in these regions. The test contributed substantially to planning of the surgical approach in each patient. The predictive alue of the amobarbital test was demonstrated by the postoperative outcome.
Predictive Value of Interictal Epileptiform Discharges During Non‐REM Sleep on Scalp EEG Recordings for the Lateralization of Epileptogenesis
Authors: Adachi Naoto , Alarcon Gonzalo , Binnie Colin D. , Elwes Robert D. C. , Polkey Charles E. , Reynolds Edward H.
Published: August 2005

Summary: Purpose: EEG recording during sleep is widely used in the assessment of epilepsy, particularly in candidates for surgery, yet the diagnostic value of this procedure is not well established. We evaluated the predictive reliability of interictal epileptiform discharges (IEDs) for localization in pre‐surgical patients with temporal lobe epilepsy (TLE) during non‐REM sleep.

Methods: Preoperative scalp EEG recordings with waking and sleep states were assessed in 83 patients with TLE in whom localization of the epileptogenic zone was subsequently confirmed by successful surgical treatment (patient seizure‐free >1 year).

Results: The accuracy of EEG recordings for prediction of lateralization significantly changed from 51.8% during waking to 78.3% during sleep. After exclusion of patients who showed no discharges, the predictive value changed from 74.1 to 86.7%. However, in patients in whom the waking scalp EEG lateralized incorrectly, no improvement in reliability was achieved by sleep recording.

Conclusions: Our results suggest that IEDs occurring in non‐REM sleep provide more accurate information for lateralization of epileptogenesis than do those occurring during waking. This gain of diagnostic information was obtained in patients who showed either bilateral or no discharges in waking records, because unilateral discharges arising de novo in sleep were always correctly lateralizing. On the other hand, in patients who showed unilateral discharges in the awake state, whether ipsilateral or contralateral to the epileptogenic zone, the findings were generally unchanged during sleep.
Halothane as a Neuroprotectant During Constant Stimulation of the Perforant Path
Authors: Walker M. C. , Perry H. , Scaravilli F. , Patsalos P. N. , Shorvon S. D. , Jefferys J. G. R.
Published: August 2005

Summary: Purpose: To determine the neuroprotective effects of halothane during constant stimulation of the perforant path.

Methods: Male Sprague‐Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer under halothane anaesthesia (1‐2% in oxygen). They were then divided into four groups. In group 1 (n = 9), the perforant path was stimulated at 20 Hz for 2 h under halothane anaesthesia (1‐2%). In group 2 (n = 3), the animals were unstimulated but maintained under halothane anaesthesia (1‐2%) for 2 h with the electrodes in place. Both groups 1 and 2 had the electrodes removed and were then allowed to recover fully from the anaesthetic. In groups 3 and 4, the electrodes were held in place with dental acrylic. Both of these groups were allowed to recover fully from anaesthesia. In group 3 (n = 3), 24‐48 h after recovery from anaesthesia, the perforant path was stimulated at 20 Hz for 2 h. Group 4 (n = 3) received no stimulation. After 14‐17 days, the rats were killed, and morphometry and cell counts were performed on the hippocampi from rats in groups 1 and 2.

Results: Cell densities were not significantly different between control (group 2), unstimulated rats, and animals stimulated under halothane anaesthesia (group 1). Stimulation in the unanaesthetised rats resulted in severe neuronal loss in hilus, CA1, and CA3.

Conclusions: Halothane protects hippocampal neurons against damage induced by constant stimulation of the perforant path.
Clinical Patterns of Patients with Temporal Lobe Epilepsy and Pure Amygdalar Atrophy
Authors: Guerreiro C. , Cendes F. , Li L. M. , Jones‐Gotman M. , Andermann F. , Dubeau F. , Piazzini A. , Feindel W.
Published: August 2005

Summary: Purpose: MRI volumetric measurements (MRIvol) have been proven reliable in determining mesial temporal atrophy in patients with TLE. We attempted to correlate the clinical features with different patterns of hippocampal formation (HF) and amygdala (AM) atrophy in patients with TLE without foreign tissue lesion.

Methods: We studied 65 patients with refractory TLE. They were divided into five groups according to MRIvol results: pure AM atrophy (n = 1 1, 10 unilateral and one bilateral), unilateral HF atrophy (n = 16), bilateral HF atrophy (n = 12), unilateral AM+HF atrophy (n = 13), and patients with normal volumes of AM and HF (n = 13). MRIvol of AM and HF were performed by using a protocol previously described by Watson et al. (Neurology 1992;42: 1743–50).

Results: Patients with AM atrophy had later onset of seizures compared with those with unilateral HF atrophy (p < 0.01). History of febrile convulsions (p < 0.0001) and frequent secondarily generalized tonic‐clonic seizures (GTCSs) were more often found in patients with HF atrophy compared with those with pure AM atrophy and those with normal volumes (p = 0.04). Prolonged postictal confusion was more often found with AM atrophy (p = 0.05). Memory impairment was more severe in patients with HF atrophy than in those with AM atrophy only or in those with normal volumes (p = 0.03). There were no significant differences among the five groups in the following parameters: age, duration of epilepsy, seizure frequency, and presence and type of aura.

Conclusions: Prolonged postictal confusion appeared to be related to AM atrophy, in keeping with previous clinical observations. These patients also had a lower incidence of early febrile convulsions, older age at epilepsy onset, lower frequency of secondary GTCS, and lesser memory dysfunction compared with patients with hippocampal atrophy.
Family Interactions as Targets for Intervention to Improve Social Adjustment After Epilepsy Surgery
Authors: Langfitt John T. , Wood Beatrice L. , Brand Kerry L. , Brand Jennifer , Erba Giuseppe
Published: August 2005

Summary: Purpose: To identify family interactions associated with psychosocial outcome of epilepsy surgery, to design interventions to improve patient outcome.

Methods: A cross‐sectional, case series study of relations among observed family behavior and psychosocial outcome of 43 patients after temporal lobectomy. Videotaped family behavior during family discussion tasks was rated for predominant family affect, affective range, and support of patient autonomy. Multiple regression analyses tested the relation of observed family characteristics to outcomes, controlling for seizure control and other psychological and disease characteristics.

Results: Predominant family affect predicted patients' social adjustment independent of postoperative seizure status and other disease characteristics. The relation between predominant affect and social adjustment was stronger among patients with persisting complex partial seizures (CPSs; r =−0.91), versus patients with auras (r =−0.38) and seizure‐free patients (r =−0.28; multiple R = 0.71; p < 0.05). Families with a positive affective climate supported patients' autonomy.

Conclusions: Two potential targets were identified for family intervention to improve postsurgical social adjustment: (a) family interactions that support a predominantly positive affective climate, and (b) family interactions that support patient autonomy. These findings are consistent with findings in normal and other clinical populations. They identify specific interactions that give rise to positive versus negative affective climate and support versus undermining of autonomy. These results lay the groundwork for intervention studies targeting these specific family interactions. Such intervention studies would clarify the direction of effect of the observed relationships and would test the efficacy of family intervention for improving psychosocial outcomes for patients with epilepsy.
Quantitative EEG Analyses and Surgical Outcome After Corpus Callosotomy
Authors: Matsuzaka Tetsuo , Ono Kenji , Baba Hiroshi , Matsuo Mitsuhiro , Tanaka Shigeki , Kamimura Naohisa , Tsuji Yoshiro
Published: August 2005

Summary: Purpose: To clarify the relation between quantitative electroencephalogram (EEG) findings and outcome following corpus callosotomy (CC).

Methods: The degree of bilateral synchrony and morphologic similarity of spike‐wave discharges was analyzed by using a cross‐correlation analysis and the measurements of amplitude differences between bilateral homologous regions in 22 patients who underwent anterior CCs for intractable symptomatic generalized epilepsies (SGE; 17 patients) and frontal lobe epilepsy (five patients).

Results: Interictal generalized synchronous spike‐wave (GSSW) bursts in the SGE patients were disrupted and changed to unilateral spike‐waves (USWs) in 11 patients and to bilaterally independent spike‐waves (BISWs) in six. The USW group had better surgical outcome than the BISW group. Preoperatively, the USW group had significantly lower interhemispheric synchrony (IS) and fewer regional changes in the side leading in time and the side dominant for amplitude, suggesting unilaterally predominant epileptogenesis that triggered the secondary bilateral synchrony. Postoperatively, the BISW group had a more marked reduction in IS because of independent discharges from bilateral epileptogenic areas, and the USW group had a greater amplitude difference because of unilateralized spike‐waves. In addition, an excellent surgical outcome was related to (a) the preoperative degree of the morphologic similarity of the bilateral spike‐waves (only a small variation during a burst of spike‐waves) and the few instances of regional changes in the side leading in time and in the side dominant for amplitude; and (b) to large postoperative amplitude differences.

Conclusion: Preoperative quantitative EEG analyses enabled us to predict the underlying conditions of epileptogenesis and the surgical outcomes in patients undergoing CC.
Surgery for the Treatment of Medically Intractable Infantile Spasms: A Cautionary Case
Authors: Shields W. Donald , Shewmon D. Alan , Peacock Warwick J. , LoPresti Christine M. , Nakagawa JoAnne , Yudovin Sue
Published: August 2005

Summary: The most appropriate time to consider cortical resection to treat medically intractable infantile spasms has not been clearly defined. The risks that need to be reconciled to make this decision are: What is the risk of loss of developmental potential if surgery is delayed too long versus what is the risk of unnecessary surgery if it is done too soon. We propose that, in addition to evaluation of seizures, developmental assessment is a key factor in the surgical decision. The case report illustrates this concept.

Case Report: HC had onset of seizures at 9 days of age and developed infantile spasms due to mild right hemimegancephaly. At 19 months, she was having up to 50 seizures/day and was evaluated and approved for right hemispherectomy but surgery was delayed. Despite the seizures, her development had been much better than most patients with hemimegencephaly and infantile spasms. At 25 months her seizure control was much improved but she had several seizures/week. EcoG at the time of surgery did not demonstrate the usual abnormalities so no resection was performed. She has had only 5 seizures in the 2½ year since.

Conclusions: (a) Hemimegalencephaly is not always associated with severe mental retardation; (b) normal or near‐normal development may, in some cases, indicate the possibility of medical control of seizures as the child grows; (c) a localized developmental brain abnormality in a child with intractable seizures should not necessarily lead to cortical resection; and (d) when a child meets developmental milestones, it may be appropriate to delay surgical intervention.
Intractable Epilepsy as the Initial Manifestation of Neurosyphilis
Authors: Phan Thanh G. , Somerville Ernest R. , Chen Sharon
Published: August 2005

Summary: A 29‐year‐old man experienced intractable partial seizures as the initial manifestation of neurosyphilis. The diagnosis was made after the onset of dementia 9 months later. Both the epilepsy and dementia resolved with penicillin therapy. Syphilis should be considered in patients with adult‐onset focal epilepsy, particularly if there is associated dementia. Treatment may be successful even when the diagnosis is delayed.
Status Epilepticus: An Overview of the Clinical Problem
Authors: Lowenstein Daniel H.
Published: August 2005

Status epilepticus has been recognized since antiquity. The terms état de mal and “status epilepticus” are derived from the slang used by epilepsy patients housed in Salpêtrière and Bicêtre hospitals in Paris during the 1800s. The definition of status epilepticus has been evolving, and is still not precise. In 1903–04 it was described as a development of epilepsy in which seizures are so frequent that “coma and exhaustion are continuous between seizures.” In 1964 the International League Against Epilepsy adopted the definition “a seizure [that] persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition.” 30 min has been the most common specified duration of seizures for the diagnosis of status epilepticus, although a duration of 10 or 20 min has been suggested as well. However, a new set of definitions for generalized, convulsive status epilepticus in adults has been proposed and includes an operational definition (specifying a seizure duration of a least 5 min) and a mechanistic definition. In the future, laboratory tests will provide the means for detecting and defining the critical factors that distinguish a single epileptic seizure from status epilepticus. Recent epidemiological studies suggest status epilepticus occurs in 100,000 to 150,000 people in the US each year, and is associated with substantial morbidity and mortality. Etiology, duration of the seizures, and the patient's age seem to be important determinants of the outcome in status epilepticus.
Wavelength Dependence of Photoparoxysmal Responses in Photosensitive Patients with Epilepsy
Authors: Takahashi Yukitoshi , Fujiwara Tateki , Yagi Kazuichi , Seino Masakazu
Published: August 2005

Purpose: We tried to specify the relation between the photoparoxysmal response (PPR) and the wavelength spectra of flashing light in various photosensitive epileptic syndromes in the physiologic state.

Methods: Intermittent photic stimulation (IPS) by a Grass PS22 photic stimulator was performed with wavelength‐specific optical filters in photosensitive patients with epilepsy (idiopathic generalized epilepsy, IGE; hereditary dentatorubral‐pallidoluysian atrophy, DRPLA) and photosensitive subjects without epilepsy.

Results: Five of 19 normal trichromat patients with IGE and an IGE patient with deuteranomaly showed wavelength‐dependent PPRs. The wavelength‐dependent PPRs were elicited only by IPS containing wavelength spectra ∼700 nm in the normal trichromat patients. Two of four patients with DRPLA showed wavelength‐dependent PPRs, and two other DRPLA patients showed quantity‐of‐light‐dependent PPRs. Quantity‐of‐light‐dependent PPRs are elicited by IPS containing more than a certain quantity of light, independent of the wavelength composition of the flashing light. Two of five subjects without epilepsy showed wavelength‐dependent PPRs.

Conclusions: There are wavelength‐dependent and quantity‐of‐light‐dependent pathophysiologic mechanisms for eliciting PPRs by low‐luminance IPS. Consideration of the quantity and wavelength composition of light from electronic screens will lead to the prevention of photosensitive seizures induced by electronic screen games.
Callosotomy for Epilepsy After West Syndrome
Authors: Pinard J. M. , Delalande O. , Chiron C. , Soufflet C. , Plouin P. , Kim Y. , Dulac O.
Published: August 2005

Summary: Purpose: To analyze the results of callosotomy in 17 children with symptomatic generalized epilepsy after West syndrome, according to the different seizure types and surgical procedures, to define selection criteria for candidates to callosotomy.

Methods: Callosotomy was performed in two successive stages. Partial callosotomy, anterior in 13 and posterior in three, was followed by completion in 14 cases in all but four patients (complete callosotomy in one stage in one, no completion in three). All patients had clinical, video‐EEG, and neuropsychological evaluation before and after each stage of callosotomy, with a mean final follow‐up of 4 years.

Results: Seizure frequency improved in only two of 13 patients after anterior callosotomy, in none of three after posterior callosotomy, but in nine of 14 after complete callosotomy. After complete callosotomy, spasms disappeared in 80% of the cases, and drop attacks, the most severe ictal event, completely stopped or were dramatically reduced in 90% of the children. One patient no longer had episodes of status epilepticus, and another one acquired the ability to walk after complete callosotomy. From the cognitive viewpoint, nine patients with improved seizure frequency after complete callosotomy also had improved behavior and cognitive functions, but two others experienced speech deterioration after posterior callosotomy at age 11 years and completion of callosotomy at age 16 years.

Conclusions: As in other severe generalized epilepsies in childhood, drop attacks provide the best indication for complete callosotomy in patients with previous West syndrome. Because drop attacks can be identifiable by falls only, the previous acquisition of walking should be considered as a key feature for any benefit to be obtained.
Effects of Pregnancy on the Pharmacokinetics of Lamotrigine in Dogs
Authors: Matar K. M. , Nicholls P. J. , Tekle A. , Bawazir S. A. , Al‐Hassan M. I.
Published: August 2005

Summary: Purpose: This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG).

Methods: Five pregnant dogs were given a daily dose of LTG (100 mg) for a period of 1 week. Two months after parturition, the same subjects were given the LTG dose (100 mg) over the same period. On both occasions, plasma LTG concentrations were determined by a sensitive, high‐performance liquid chromatographic (HPLC) method, over a 30‐h period after the last dose.

Results: The mean maximum plasma concentration (Cmax), volume of distribution (Vd/F), and oral body clearance (Cl/F) for LTG (± SD) during pregnancy were 7.63 ± 2.46 μg/ml 1.74 ± 0.29 L/kg, and 0.19 ± 0.04 L/h/kg, respectively. After pregnancy, the same variables were 6.12 ± 2.24 μg/ml, 2.36 ± 1.10 L/kg, and 0.30 ± 0.13 L/h/kg, respectively. None of these pharmacokinetic parameters was found to be significantly different between the two groups.

Conclusions: The apparent lack of change in the relevant pharmacokinetic parameters of LTG during pregnancy may indicate that pregnancy has little or no effect on glucuronidation; the principal pathway for the drug's elimination.
Epileptiform Propagation Patterns Mediated by NMDA and Non‐NMDA Receptors in Rat Neocortex
Authors: Telfeian Albert E. , Connors Barry W.
Published: August 2005

Summary: Purpose: The neocortex can generate various forms of epileptiform activity, including one that depends on N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptors (NMDARs), and another dependent on non‐NMDA‐type (AMPA) glutamate receptors (AMPARs). Previous work in vitro suggests that both forms of activity are initiated by neurons of layer 5, but the spatial patterns of horizontal propagation have been studied only for the AMPAR form. We have tested the hypothesis that both types of epileptiform activity spread via common pathways in one cortical layer, suggesting that lamina‐specific intervention might selectively interrupt both.

Methods: Slices of rat somatosensory cortex were maintained in vitro and treated with the γ‐aminobutyric acid type A (GABAA)‐receptor antagonist picrotoxin. Single all‐or‐none epileptiform discharges were evoked with an electrical stimulus, and extracellular microelectrodes were used to track the vertical and lateral spread of the discharges.

Results: In both high and low concentrations of picrotoxin, the non‐NMDAR antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) completely blocked propagation, whereas the NMDAR antagonist D‐2‐amino‐5‐phosphonovaleric acid (DAPV) only shortened the duration of discharges. When extracellular [Mg2+] was reduced in the presence of picrotoxin and CNQX, NMDAR‐dependent epileptiform discharges could be initiated. NMDAR‐dependent discharges spread at about one fifth the conduction velocity of AMPAR‐dependent events. Analysis of spatiotemporal field‐potential patterns suggested that both NMDAR‐ and AMPAR‐mediated propagation involved early activity in layers 5 and 6, followed by larger‐amplitude activity in upper cortical layers along the path of propagation.

Conclusions: Our results imply that a common pathway mediates the propagation of these two forms of epileptiform activity, and suggests that lamina‐specific surgical intervention might maximize anticonvulsant effect while minimally disrupting cortical function.
NMDA‐ But Not Kainate‐Mediated Events Reduce Efficacy of Some Antiepileptic Drugs Against Generalized Tonic‐Clonic Seizures in Mice
Authors: Urbanska Ewa M. , Tomczyk Tomasz , Haberek Grzegorz , Pilip Slawomir , Matyska Joanna , Turski Waldemar A. , Kleinrok Zdzislaw , Czuczwar Stanislaw J.
Published: August 2005

Summary: Purpose: The aim of this study was to evaluate the efficacy of conventional antiepileptic drugs (AEDs) against the generalized tonic‐clonic seizures in mice subjected to the subconvulsive doses of N‐methyl‐D‐aspartate (NMDA) or kainate.

Methods: Mice were given NMDA and kainate in the doses of 50.0 and 9.0 mg/kg i.p., respectively [i.e., equal to 75% of their CD16 values (convulsive dose in 16% of the animals studied)]. Subsequently the anticonvulsive potential of conventional AEDs against the maximal electroshock‐induced seizures was estimated. Where necessary, the plasma levels of AEDs were assessed.

Results: NMDA or kainate application did not affect the electroconvulsive threshold. NMDA, but not kainate, diminished the antiepileptic activity of diazepam (DZP) and carbamazepine (CBZ), increasing their 50% effective doses (ED50S) from 14.1 and 8.6 to 19.0 and 12.1 mg/kg i.p., respectively. Neither NMDA nor kainate affected the ED50 for valproate (VPA), phenobarbital (PB), or diphenylhydantoin (DPH) against electroconvulsions. NMDA‐evoked effects were reversed with the use of the NMDA antagonist, D‐(E)‐2‐amino‐4‐methyl‐5‐phosphono‐3‐pentenoic acid (CGP 40116) and were not accompanied by the alterations in the free plasma levels of AEDs.

Conclusions: The NMDA‐mediated events, but not kainate‐related ones, seem to be involved in the protective action of DZP and CBZ against maximal electroshock‐induced seizures. Moreover, it might be concluded that when subthreshold activation of NMDA receptors adds to other epileptogenic factors, DZP and CBZ are less efficacious. Presented data indicate that in such situations, adding the NMDA receptor antagonist (at very low doses) to the AED may yield beneficial therapeutic effects.
Gamma Knife Surgery for Mesial Temporal Lobe Epilepsy
Authors: Régis Jean , Bartolomei Fabrice , Rey Marc , Genton Pierre , Dravet Charlotte , Semah Franck , Gastaut Jean‐Louis , Chauvel Patrick , Peragut Jean‐Claude
Published: August 2005

Summary: Purpose: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. All the well‐documented radiosurgery of epilepsy cases are epilepsies associated with tumors or arteriovenous malformations (AVMs). Results prompted the idea to test radiosurgery as a new way of treating epilepsy without space‐occupying lesions.

Methods: To evaluate this new method, we selected seven patients with drug‐resistant “mesial temporal lobe epilepsy” (MTLE). The preoperative evaluation program was the one we usually perform for patients selected for microsurgery of TLE [video‐EEG analysis of seizures, foramen ovale electrode recording, magnetic resonance imaging (MRI) positron emission tomography (PET) scan, neuropsychological testing]. In lieu of microsurgery, the amygdalohippocampectomy was performed by using GK radiosurgery.

Results: Morphologic (MRI) signs of destruction of the target took place at 9 months after GK surgery. Since the treatment day, the first patient has been seizure free. Seizure improvement came more gradually for the following patients, and complete cessation of seizures occurred around the tenth month (range, 8–15 months). MRI shows that the amygdaloentorhinohippocampal target was selectively injured. No significant side effect (except one case of homologous quadrantanopia) or morbidity and no mortality was observed. The current follow‐up is 24–61 months, and all (but one) patients are seizure free.

Conclusions: This initial experience proves clearly the short‐to middle‐term efficiency and safety of GK for MTLE surgery. These results need further confirmation of long‐term efficiency, but the introduction of GK surgery into epilepsy surgery can reduce dramatically its invasiveness and morbidity.
Validity of Diagnosis Using the French Translation of the Semi‐Structured Interview for Seizure Classification
Authors: Picot Marie‐Christine , Crespel Arielle , Tricot Marie , Daurès Jean‐Pierre , Valton Luc , Malafosse Alain , Baldy‐Moulinier Michel
Published: August 2005

Summary: Purpose: The purpose of this study was to assess the acceptability and validity of the French cross‐cultural translation of a semistructured interview for seizure classification (SISC). We used the first revised version, the original of which was validated in 1990.

Methods: We administered the French SISC to a sample of 67 adults older than 15 years, comprising 17 controls and 50 patients with epilepsy (without provoked or isolated seizures). A cross‐cultural translation was made from American English into French. Medical records were reviewed by epileptologists, who classified seizures, syndromes, and risk factors in accordance with the International League Against Epilepsy (ILAE) classifications. Agreement between interview‐ and physician‐based diagnoses was assessed with a kappa coefficient (K) at each level of the recognized schemes for the classification of seizures (both broad and specific categories), syndromes, and risk factors.

Results: The sensitivity of the French SISC in diagnosing an epileptic seizure was 100%, with a specificity of 94%. Interview‐based diagnoses agreed with those of physicians in 90% of patients for broad seizure categories [ie, generalized or focal in origin (K = 0.74)]. When diagnoses agreed on focal origin, the agreement on seizure types—simple or complex—was 91% (K = 0.84). Among generalized seizures, the agreement was 73% (K = 0.60). Agreement on epilepsy syndromes was excellent for generalized epilepsy but moderate for focal epilepsy. Agreement on identified risk factors was 93%.

Conclusions: The K coefficients demonstrated a good level of reliability. These results support the acceptability of this type of interview and the validity of the French version of the SISC.
Felbamate in Experimental Model of Status Epilepticus
Authors: Mazarati Andrey M. , Baldwin Roger A. , Sofia R. Duane , Wasterain Claude G.
Published: August 2005

Summary: Purpose: To examine the putative seizure‐protective properties of felbarnate in an animal model of self‐sustaining status epilepticus (SSSE).

Methods: SSSE was induced by 30‐min stimulation of the perforant path (PPS) through permanently implanted electrodes in free‐running male adult Wistar rats. Felbarnate (FBM; 50, 100, and 200 mg/kg), dizepam (DZP; 10 mg/kg), or phenytoin (PHT; 50 mg/kg) were injected i.v. 10 min after SSSE induction. Electrographic manifestations of SSSE and the severity of SSSE‐induced neuronal injury were analyzed.

Results: Felbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose‐dependent manner. Total time spent in seizures after FBM and 290 ± 251 min (50 mg/kg), 15.3 ± 9 min (100 mg/kg), and 7 ± 1 min (200 mg/kg), whereas control animals spent 410 ± 133 min seizing. This effect of FBM was stronger than that of DZP (10 mg/kg, 95 ± 22 min) and comparable to that of PHT (50 mg/kg, 6.3 ± 2.5 min). In the applied doses, FBM (200 mg/kg) was more effective than PHT (50 mg/kg) or DZP (10 mg/kg) in shortening seizure duration and decreasing spike frequency, when administered on the pleateau of SSSE (injection 40 min after the end of PPS). Anticonvulsant action of FBM was confirmed by milder neuronal injury compared with control animals.

Conclusions: Felbamate, a clinically available AED with a moderate affinity for the glycine site of the NMDA receptor, displayed a potent seizure‐protective effect in an animal model of SSSE. These results suggest that FBM might be useful when standard AEDs fail in the treatment of refractory cases of SE.
Can Early Postnatal Closed Head Injury Induce Cortical Dysplasia?
Authors: Lombroso Cesare T.
Published: August 2005

Summary: Purpose: Increased availability of surgically resected epileptogenic tissues reveals often unsuspected cortical dysplasia (CD). There is some controversy about the ontogenic stages in which these occur. Although most take place during neuroblast proliferation and migration, there is some evidence for some CD occurring during postmigrational intrinsic cortical organization. It has been shown that various kinds of focal cortical manipulations in rats, if performed within 3–4 postnatal days, lead to the genesis of various cortical malformations including a four‐layered microgyrus or an unlayered CD. It is not known whether such events also might occur in the human brain.

Methods: Two children sustained minor head trauma within 4 postnatal days and later developed intractable epilepsy, which was relieved by surgery. Neuropathologic analysis of the resected tissues revealed an unsuspected microdysplastic cortex immediately adjacent to a focal, modest meningeal fibrosis, presumably secondary to the old closed head trauma.

Results: The main histologic features were a disorganized, unlayered cortex; abnormal clusters of neurons, often with complex, randomly oriented proximal dendritic patterns with absent apical orientation; the presence of a number of heterotopic small and large neurons in the white matter; absence of inflammatory infiltrates, of hemosiderine, of reactive gliosis, or of an excessive number of blood vessels. The morphologic features in these surgical specimens suggest that these focal malformations occur because of a regional disorder of postmigrational intrinsic cortical remodeling.

Conclusions: The clinical histories and the pathologic findings lend some support to the hypothesis that minor morbid events occuring in the immediate postnatal period may lead to microdysplasia in the human similar to those induced in rat pups. The animal model could be helpful to clarify the genesis of some cases of CD and of the epileptogenicity often manifesting later in life.
Intracranial EEG Seizure‐Onset Patterns in Neocortical Epilepsy
Authors: Lee Sang‐Ahm , Spencer Dennis D. , Spencer Susan S.
Published: August 2005

Summary: Purpose: We investigated neocortical seizure‐onset patterns recorded by intracranial EEG with regard to anatomic location, pathologic substrate, and prognostic value for surgical outcome.

Methods: Seizure onset was analyzed in 53 neocortical re‐sective epilepsy surgery patients. Anatomic location was divided into temporal and extratemporal. Pathologic substrate was classified as developmental, mature, and negative or non‐specific gliosis. Onset frequency was categorized by visual analysis into tradition EEG frequency bands. Spatial extent was divided into focal (fewer than four contacts) and regional (more than five contacts). Waveform at seizure onset was divided into several types based on their morphology. Onset features were examined with respect to anatomic location, pathologic substrate, and surgical outcome.

Results: Seizure‐onset frequency was significantly related to spatial distribution and to anatomic location. Extratemporal and regional onset were more commonly in the gamma range, and temporal and focal onset in the beta frequency range or slower. Waveform could be categorized into five different patterns, of which low voltage fast activity (LVFA) was the most common form (57%). LVFA and rhythmic alpha‐theta spike activity were more common in developmental than in mature pathology, whereas rhythmic sinusoidal waves at onset were found in only mature substrates. Waveform pattern showed a possible correlation with surgical outcome (p = 0.097): LVFA and rhythmic sinusoidal waves onset patterns were associated with favorable outcome more often (40.4%) than the other three patterns (6.3%). Slow onset suggested poor outcome in the subgroup of developmental pathology (p = 0.062).

Conclusions: Certain electrographic seizure‐onset features are associated with specific substrates and outcomes, whereas others reflect the anatomic location and its connections independent of the pathology.
The Role of the Intracarotid Amobarbital Procedure in Evaluation of Patients for Epilepsy Surgery
Authors: Spencer David C. , Morrell Martha J. , Risinger Michael W.
Published: August 2005

Purpose: To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization‐related epilepsy.

Methods: We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance.

Results: Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection.

Conclusions: In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by non‐invasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.
Role of Nitric Oxide in Pentylenetetrazol‐Induced Seizures: Age‐Dependent Effects in the Immature Rat
Authors: de Vasconcelos Anne Pereira , Gizard Florence , Marescaux Christian , Nehlig Astrid
Published: August 2005

Summary: Purpose: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)‐induced seizures in immature rats.

Methods: Four cortical electrodes were implanted in 10‐day‐old (P10) and 21‐day‐old (P21) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of NG‐nitro‐l‐arginine methyl ester (l‐NAME; 10 mg/kg) and 7‐nitroindazole (7NI; 40 mg/kg), two NO synthase (NOS) inhibitors, and l‐arginine (l‐arg; 300 mg/kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate.

Results: At P10, the postseizure mortality rate increased from 18–29% for the rats receiving PTZ only to 100% and 89% for the rats receiving l‐NAME and 7NI, respectively; whereas l‐arg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82–89% mortality rate induced by PTZ alone, whereas l‐arg decreased the mortality rate to 29%. In addition, all NO‐related drugs increased the duration of ictal activity at P10, whereas at P21, L‐arg and L‐NAME affected the first seizure type, producing clonic seizures with L‐arg and tonic seizures with L‐NAME.

Conclusions: The relative natural protection of very immature rats (P10) against PTZ‐induced deaths could be linked to a high availability of L‐arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO‐related compounds may be related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of clonic seizures.
Absence Seizures with Evolution into Generalized Tonic–Clonic Activity: Clinical and EEG Features
Authors: Mayville Christina , Fakhoury Toufic , Abou‐Khalil Bassel
Published: August 2005

Summary: Purpose: To report the clinical and electrographic features of absence seizures evolving into generalized tonic‐clonic (GTC) activity in six patients with idiopathic generalized epilepsy.

Methods: All patients were referred for evaluation of refractory seizures and underwent video‐EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video‐EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients.

Results: All patients were women, with a mean age of 27 years (range, 14–43 years). The mean age at seizure onset was 12 years (range, 5–15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5‐ to 5‐Hz spike‐and‐wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2‐ to 5‐Hz spike‐and‐wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow‐up period of 12–36 months.

Conclusions: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.
Changes in Benzodiazepine Binding in a Subkindling Situation
Authors: Rössler Anne‐Sophie , Launay Jean‐Marie , Venault Patrice , Dodd Robert H. , Chapouthier Georges
Published: August 2005

Summary: Purpose: A low dose of the benzodiazepine receptor inverse agonist methyl β‐carboline‐3‐carboxylate (β‐CCM) (1 mg/kg) was used to assess [3H]‐flumazenil binding in a subkindling situation in Swiss mice.

Methods: The brains were removed, and benzodiazepine receptor binding was studied every second day over 14 days of administration.

Results: With each successive trial, Bmax values showed a steady and significant decrease, whereas Kd values showed a steady and significant increase. Behavioral data showed that at this low dose, actual kindling (seizuring) was not reached at the behavioral level.

Conclusions: The findings suggest that decreased γ‐amino‐butyric acid (GABA) inhibition may occur even if behavioral effects of kindling are not observed.
Effect of Levetiracetam on Epilepsy‐Related Quality of Life
Authors: Cramer Joyce A. , Arrigo Celestina , Van Hammée Geneviève , Gauer Laura J. , Cereghino James J. ,   for the N132 Study Group
Published: August 2005

Summary: Purpose: To evaluate the short‐term effect of levetiracetam (LEV; UCB L059) as add‐on therapy on health‐related quality of life in the treatment of refractory partial‐onset seizures.

Methods: Patients were enrolled in protocol UCB N132 if they had 12 partial‐onset seizures with or without secondary generalization during the 12‐week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31‐item Quality of Life in Epilepsy (QOLIE‐31) questionnaire was completed by 246 patients at the end of baseline and at 18‐week follow‐up, or earlier if withdrawn.

Results: Significant differences were found among the three treatment groups for Seizure Worry (p = 0.0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (10% change from baseline to follow‐up) was perceived by LEV 3,000 mg responders in all areas, except Emotional Well‐Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas.

Conclusions: Addition of LEV to standard medication seems to have a positive impact on health‐related quality of life, particularly among responders in this short‐term study. These exploratory analyses require additional studies to evaluate long‐term changes in a larger population.