bluuebunny/crossref_metadata_2025 huggingface dataset:
Quisqualic Acid‐Induced Seizures During Development: A Behavioral and EEG Study
Authors: Thurber Samuel J. , Mikati Mohamad A. , Stafstrom Carl E. , Jensen Francis E. , Holmes Gregory L.
Published: October 2005

Summary: Quisqualic acid (QA) is an excitatory amino acid analogue that binds to the glutamate ionotropic receptor subclass AMPA (a–amino–3 hydroxy‐5 methyl‐4 isoxazol propionic acid) and metabotropic receptor phos‐pholipase C. To study its epileptogenic properties, we administered QA through an intraventricular cannula to 23‐, 41‐, and 60‐day‐old rats with recording electrodes implanted in amygdala, hippocampus, and neocortex. The frequency power spectra of the recorded EEG was computed by fast fourier transform (FFT), and coherence between anatomic sites was computed. Seizures occurred in all animals receiving QA. The behavioral manifestations of the seizures varied as a function of age, with younger rats demonstrating rigidity and immobility followed by circling activity and intermittent forelimb clonus and 60‐day‐old animals exhibiting severe, wild running followed by generalized clonus. Ictal electrical discharges occurred in all animals. Neocortical ictal discharges occurred more prominently in the younger animals, and amygdala ictal discharges were more prominent in the older animals. Marked increases in spectral power occurred during the seizures in all anatomic structures and at all frequencies. Our results demonstrate that the clinical manifestations of QA seizures vary during development; results of the neurophysiologic studies suggested that neocortex may play an important role in genesis of QA seizures in immature brain.
Role of 5‐Hydroxytryptamine Receptor Subtypes in the 1‐[3‐(Trifluoromethyl)Phenyl] Piperazine‐Induced Increase in Threshold for Maximal Electroconvulsions in Mice
Authors: Przegaliński Edmund , Baran Leokadia , Siwanowicz Joanna
Published: October 2005

Summary: The effect of l‐[3‐(trifluoromethyl)phenyl] piperazine (TFMPP), a 5‐hydroxytryptamine (5‐HT) receptor agonist, on the threshold for maximal electroconvulsions was studied in mice. TFMPP in intraperitoneal (Lp.) doses of 10, 20 and 40 mg/kg increased the convulsive threshold (the amperage necessary to produce the hindlegtonic extensor component of seizures in 50% of animals) by 28, 60, and 85%, respectively. The effect of TFMPP (20 mg/kg) was dose‐dependently blocked by 142‐methoxyphenyl)‐4‐[4‐(2‐phthalimido)butyl] piperazine (NAN‐190), prazosin, spiperone, mesulergine, ketanserin, and ritanserin. On the other hand, pindolol and cyanopindolol had no effect on the convulsive threshold increased by TFMPP. The results indicate that the TFMPP‐induced decrease in the susceptibility to seizures is connected to stimulation of 5‐HT2 or of both 5‐HT1c and 5‐HT2 receptors. Moreover, α1‐adrenoceptors also appear to be engaged in this effect.
Automated EEG Monitoring in Defining a Chronic Epilepsy Model
Authors: Mascott Christopher R. , Gotman Jean , Beaudet Alain
Published: October 2005

Summary: There has been a recent surge of interest in chronic animal models of epilepsy. Proper assessment of these models requires documentation of spontaneous seizures by EEG, observation, or both in each individual animal to confirm the presumed epileptic condition. We used the same automatic seizure detection system as that currently used for patients in our institution and many others. Electrodes were implanted in 43 rats before in‐traamygdalar administration of kainic acid (KA). Animals were monitored intermittently for 3 months. Nine of the rats were protected by anticonvulsants [pentobarbital(PB) and diazepam (DZP)] at the time of KA injection. Between 1 and 3 months after KA injection, spontaneous seizures were detected in 20 of the 34 unprotected animals (59%). Surprisingly, spontaneous seizures were also detected during the same period in 2 of the 9 protected animals that were intended to serve as nonepileptic controls. Although the absence of confirmed spontaneous seizures in the remaining animals cannot exclude their occurrence, it indicates that, if present, they are at least rare. On the other hand, definitive proof of epilepsy is invaluable in the attempt to interpret pathologic data from experimental brains.
Charles Dickens and Epilepsy
Authors: Cosnett J. E.
Published: October 2005

Summary: Through some characters in his novels, Charles Dickens recorded observations on the nature of epileptic seizures, their causes and provocation, and their consequences. Three of his main characters, Monks, Guster, and Bradley Headstone, had seizures which Dickens realistically described.
Effect of Kainic Acid on Unit Discharge in CA1 Area of Hippocampal Slice of DBA and C57 Mice
Authors: Wang Zhian , Chow Sien‐Yao
Published: October 2005

Summary: Spontaneous unit discharges in stratum pyramidale of CA1 area of hippocampal slices from DBA and CS7 mice at different ages were recorded extracellularly. The average rate and amplitude of the spontaneous discharges from CA1 area of hippocampal slices bathed in artificial cerebrospinal fluid (aCSF) were not different between DBA and CS7 mice at either 3–4 or 5–6 weeks of age. Bath application of kainic acid (KA) in concentrations of 0·5–1·0 μM produced different responses in CA1 area from these two strains of mice. In DBA mice at age 3–4 weeks, when they are most susceptible to audiogenic seizures, KA perfusion induced high‐frequency repetitive single spikes and bursts of multiple population spikes in CA1 area. Very high‐frequency discharges (10‐fold higher than most responses) were also observed in 20% of all slices. In audiogenic seizure resistant CS7 mice at age 3–4 weeks, KA perfusion at the same doses induced only the repetitive single spikes. The rate of spontaneous discharges was much lower than that in DBA mice. No burst of multiple population spikes nor very high‐frequency responses were recorded in CS7 mice. At age 5–6 weeks, when both DBA and CS7 mice are resistant to audiogenic seizures, the rate of spontaneous discharges recorded from the CAI area during and after KA perfusion was lower than that at age 3–4 weeks, and there was no significant difference between DBA and CS7 mice. Pretreatment of hippocampal slices with AMPA/kainate receptor antagonist CNQX (10 pA4) markedly reduced the rate and amplitude of spontaneous discharges in CA1 area during and after KA perfusion, whereas competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist D‐APS had no effect. These results indicate that the responses in spontaneous discharges recorded extracellularly from stratum pyramidale in CA1 area of hippocampal slices to KA perfusion correlate with susceptibility to audiogenic seizures in DBA and CS7 mice.
Facilitation of Amygdala Kindling Development and Kindled Seizures by Metaphit
Authors: Chen Nian‐Hang , Wang Congdong , Jobe Phillip C. , Reith Maarten E. A.
Published: October 2005

Summary: The effect of metaphit (a phencyclidine analogue with an acylating isothiocyanate) on kindling development and kindled seizures from amygdala was investigated in rats pretreated once with metaphit. Administration of a single dose of metaphit (10 or 20 mg/kg intraperitoneally i.p.) 4 h before the first electrical stimulation of the amygdala did not in itself induce seizures, but greatly facilitated development of behavioral seizures during kindling. This effect persisted throughout the whole process of electrical amygdala kindling without further dosing. In contrast, metaphit only transiently and modestly increased the growth of afterdischarge (AD) duration. In kindled rats, pretreatment with a single dose of metaphit (20 mg/kg) 8 h before the test stimulation reduced the threshold current required to elicit a stage 5 seizure and shortened the latency for bilateral forelimb clonus (BFC) without changing AD duration or BFC duration. The facilitation of kindling development and kindled seizures may be due to an excessive excitatory transmission by metaphit in the limbic seizure circuitry.
Localization of an Anatomic Substrate for the Anticonvulsant Activity Induced by D‐Cycloserine
Authors: Peterson Steven L.
Published: October 2005

Summary: D‐Cycloserine is a partial agonist of the strychnine‐insensitive glycine site that inhibits the tonic hindlimb extension (THE) component of maximal electroshock seizures (MES). This study determined the effect of focal D‐clycoserine microinfusion into nucleus re‐ticularis pontis oralis (RPO) on the THE component of MES in rats. Bilateral microinfusion of D‐cycloserine (50 nmol per side) into the RPO region 5.4 and 5.6 mm posterior to bregma inhibited THE in 80% of rats tested. Unilateral D‐cycloserine (50 nmol) RPO microinfusions were ineffective. Likewise, RPO microinfusion of vehicle, L‐cycloserine (50 nmol per side), or the strychnine‐insensitive glycine site antagonist 7‐chlorokynurenic acid (10 and 50 nmol per side) did not alter THE incidence. However, coinfusion of 7‐chlorokynurenic acid (50 nmol per side) with D‐cycloserine (50 nmol per side) completely antagonized the anticonvulsant activity induced by D‐CYcloserine (8 of 8 rats with THE). These data indicate that the anticonvulsant activity of D‐cycloserine is mediated by RPO. Because the anticonvulsant effect is stereospecific and is reversible by 7‐chlorokynurenic acid, these results also indicate that D‐cycloserine acts through the strychnine‐insensitive glycine site to inhibit THE.
[14C]2‐Deoxyglucose Autoradiographic Technique Provides a Metabolic Signature of Cobalt‐Induced Focal Epileptogenesis
Authors: Van Ostrand Gigi , Cooper Rod M.
Published: October 2005

Summary: Brain glucose consumption in rats with unilateral visual cortex implants of epileptogenic cobalt rods was assessed by the 2‐deoxyglucose (2‐DG) method. Nine days postoperatively, “dark patches” of higher 2‐DG uptake, bordered by tissue showing lesser uptake, were observed around the implant site. The dark patches were located just beyond the damaged perifocal zone, in normal‐appearing Nissl‐stained cortex designated by the electrocorticographic (ECoG) work of other investigators as the focus of epileptic activity. As was also predictable from earlier research, the cortical patches were prominent on day 9 and absent by day 35. Regions of high metabolic activity in thalamus, presumably the result of axonal transport of cobalt ions, were also strikingly evident in the projection nuclei connecting with the cortical implant sites. The abnormal thalamic activity is likely the metabolic counterpart of “secondary foci,” a characteristic feature of the cobalt model. The longevity of these thalamic dark patches, which developed between days 2 and 9 and did not disappear until between days 90 and 365, may account for the persistent sensitivity to seizure‐inducing drugs that occurs secondary to cobalt implants. The absence of dark patches after control non seizure‐inducing but toxic copper implants argued against the possibility that the dark patches reflected some non‐epileptogenic effect of the cobalt. As well, under pentobarbital anesthesia, the patches behaved in a manner suggesting that their 2‐DG uptake reflected neural and not glial cell activity. Dark patches are a distinctive autoradiograph signature of tissue made epileptic by cobalt.
Epilepsy in Pakistan: A Population‐Based Epidemiologic Study
Authors: Aziz H. , Ali S. M. , Frances P. , Khan M. I. , Hasan K. Z.
Published: October 2005

Summary: A house‐to‐house, cross‐sectional, population study of epilepsy on 24,130 individuals of all ages from southern Pakistan indicates an age‐specific prevalence rate of 9·99 in 1,000 (14·8 in 1,000 in rural and 7·4 in 1,000 in urban areas) for recurrent, non febrile “active” epilepsy in Pakistan. Mean onset of epilepsy was 13·3 years, and 74·3% epileptic persons were aged <19 years at onset of the disorder. The most common seizure type was ton‐icclonic in 77% [primary generalized tonic‐clonic (GTC) in 59% and secondarily generalized in 18%], simple partial (SPS) in 5%, complex partial (CPS) in 6%, generalized absence in l%, tonic in 3%, and myoclonic in 3% cases. Multiple seizure types in the same person were evident in 9·6% of only the generalized group. A putative cause could be suggested in 38·4% of cases: 32% had a positive family history of epilepsy, most common among siblings. Common perceived precipitants included fever in 29·2% and emotional disturbances in 16·6%. Only 3% of epileptic persons believed that their illness was due to supernatural causes. Treatment status was very poor, with only 2% rural and 27% urban epileptic persons receiving antiepileptic drugs (AEDs) at the time of the survey. We discuss the logistic and management problems of population‐based epidemiologic studies in developing countries.
Prenatal Events and Genetic Factors in Epileptic Patients with Neuronal Migration Disorders
Authors: Palmini André , Andermann Eva , Andermann Frederick
Published: October 2005

Summary: Because disorders of neuronal migration to cerebral cortex in humans are believed to occur in the first half of gestation, prenatal events or genetic factors are suspected to have a pathogenetic role. We evaluated this by comparing the frequency of potentially harmful prenatal events and of genetic factors in a series of 40 patients (38 with epilepsy) with neuronal migration disorders (NMD) and in 40 epileptic controls, using a predetermined standardized questionnaire to minimize interviewer bias. Potentially harmful prenatal events (significant maternal physical trauma, ingestion of medications, exposure to roentgenograms, infections, uterine or metabolic abnormalities) were reported in the pregnancy histories of 58% of patients with NMD but in only 15% of epileptic controls (p = 0·0002). In contrast, peri and postnatal potentially relevant etiologic factors were reported in the histories of only 22% of patients with NMD but in 50% of the epileptic controls (p = 0·01). Genetic factors (a family history of epilepsy, mental retardation, or congenital malformations of the CNS) were noted in 13 and 20% of the families, respectively. Stillbirths occurred only in the group with NMD, accounting for 3·06% of sibling pregnancies. The findings suggest that prenatal potentially harmful environmental events play a central role in the pathogenesis of NMD in humans.
Clinical and Electroencephalographic Evidence for Sites of Origin of Seizures with Diffuse Electrodecremental Pattern
Authors: Arroyo Santiago , Lesser Ronald P. , Fisher Robert S. , Vining Eileen P. , Krauss Gregory L. , Bandeen‐Roche Karen , Hart John , Gordon Barry , Uematsu Sumio , Webber Robert
Published: October 2005

Summary: A diffuse electrodecremental ictal pattern with other forms of epilepsy and has been considered to reflect a generalized seizure disorder of diffuse cortical or subcortical (brainstem) origin. In some seizures associated with DEP, however, focal ictal manifestations have been observed. We reviewed the records of all patients admitted to our seizure monitoring unit for 3 years and detected 39 patients with seizures associated with DEP. In 23 of 39 patients, clinical ictal behaviors resembled seizures of unilateral supero/mesiofrontal lobe origin and interictal EEG showed a prominent unilateral frontal component. Nine of 39 had complex absences (CA)/complex partial seizures (CPS); 4 of them were of unilateral frontal lobe origin. Seven of 39 patients had tonic or atonic seizures. Seven patients were studied further with subdural electrodes. Ictal onsets showed a highfrequency frontal lobe discharge. We conclude that in a subgroup of patients a generalized electrodecremental pattern on scalp EEG results from a regional cortical high‐frequency ictal discharge originating in a single frontal lobe.
Infantile Spasms: Localized Cerebral Lesions on SPECT
Authors: Miyazaki Masahito , Hashimoto Toshiaki , Fujii Emiko , Tayama Masanobu , Kuroda Yasuhiro
Published: October 2005

Summary: Ten infantile spasms (IS) patients had single photon emission computed tomography (SPECT) with [99mTc]HMPAO, EEG, and magnetic resonance imaging (MRI) studies. SPECT showed localized cerebral hypo‐perfusion in 7 infants (4 unifocal; 3 multifocal) always involving the temporal regions either unilaterally or bilaterally. EEGs obtained in near time of the SPECT studies showed focal abnormalities in all 7 infants with hypoper‐fusion on SPECT, with complete correspondence of the abnormalities in 5. MRI showed localized cerebral lesionsin only 3 of the 10 infants, all of whom had corresponding areas of hypoperfusion on SPECT. Our study indicates that localized cerebral abnormalities (especially of the temporal lobes) may often be associated with IS and that such patients may have localized cerebral hypoperfusion on SPECT even when the MRI is normal.
γ‐Vinyl‐GABA (Vigabatrin) in the Therapy of Lennox‐Gastaut Syndrome: An Open Study
Authors: Feucht M. , Brantner‐Inthaler S.
Published: October 2005

Summary: The antiepileptic effect of vigabatrin (γ‐vinyl GABA, VGB) in children has been demonstrated in controlled and open studies. According to the literature, results were good to excellent in partial seizures (with and without becoming secondarily generalized) and promising in infantile spasms (IS). In patients with myoclonic epilepsies of early childhood and especially those with Lennox‐Gastaut syndrome (LGS), the effect of VGB has been investigated only to a limited extent and the pattern of response was variable. The present open, add‐on, dose‐ranging study was initiated to assess the long‐term effect and safety of VGB in a cohort of 20 children with LGS who were not responding sufficiently to first‐line drug monotherapy with valproate (VPA) instead of adding classical second‐line antiepileptic drugs [AEDs: benzodiazepines (BZD), phenobarbital (PB), primidone (PRM)], which usually are associated with rapid diminution of their antiepileptic properties and a high frequency of side effects. Eighty‐five percent of children experienced a 50–100% reduction in seizure frequency, even after dose reduction of VPA. No serious side effects occurred except in 1 patient who experienced dyskinesia. Mood changes, sedation, ataxia, and hypersalivation, well‐known complications of other AEDs, were not observed.
γ‐Vinyl GABA (Vigabatrin) and Mood Disturbances
Authors: Aldenkamp A. P. , Vermeulen J. , Mulder O. G. , Overweg J. , Van Parys J. A. P. , Beun A. M. , Van't Slot B.
Published: October 2005

Summary: We explored factors that may predispose patients to adverse mood effects during treatment with vigabatrin (γ‐vinyl GABA; VGB): mood disorders before VGB treatment, type of epilepsy, seizure type and seizure frequency, type and number of comedication, and VGB dose. The clinical relevance of such a study is that it may help identify circumstances in which VGB should be administered with caution. Seventy‐three patients (40 males, 33 females), all with refractory epilepsies, who received VGB as add‐on therapy, were assessed by the Amsterdamse Stemmingslyst (ASL), a mood‐rating scale, before the start of treatment, and demographic and clinical data were recorded. The patients were followed for 6 months after the start of VGB treatment. Treatment with VGB had to be discontinued in 38 patients (52% of the total sample). Mood problems were the main reason for discontinuation in 9 (12·3% of the total sample). In 6 other patients, mood problems were mentioned as the reason for discontinuing treatment, in combination with lack of drug efficacy. Development of adverse mood effects could not be predicted by a specific mood profile on the ASL. Before treatment, the “mood problems discontinuation group” did not show extreme scores for any assessed areas of mood and no significant differences from other patients were noted on the mood scales. Neither did clinical or demographic data show statistically confirmed specific characteristics for the mood problems discontinuation group, though the patients tended to use more antiepileptic drugs (AEDs) as cotherapy, to have a slightly lower daily dose of VGB, to be slightly older, and were mostly female. Especially the trend toward a relation with AED as comedication deserves further study.
Severe Hepatotoxicity During Valproate Therapy: An Update and Report of Eight New Fatalities
Authors: St. König A. , Siemes H. , Bläker F. , Boenigk E. , Groß‐Selbeck G. , Hanefeld F. , Haas N. , Köhler B. , Koelfen W. , Korinthenberg R. , Kurek E. , Lenard H‐G. , Penin H. , Penzien J.M. , Schünke W. , Schultze C. , Stephani U. , Stute M. , Traus M. , Weinmann H.‐M. , Scheffner W.
Published: October 2005

Summary: Since our last report on valproate (VPA)‐related hepatotoxicity in 1988, 8 other children have died of VPA‐associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty‐five percent of patients with fatal liver failure were normally developed, 23.5% were receiving VPA monotherapy, and 35·3% were aged s2 years. The initial clinical symptoms of VPA‐related hepatotoxicity were nausea, vomiting, apathy or coma, and increasing seizures in more than 50% of patients, in combination with febrile infections at onset of symptoms. As compared with the series of German patients reported in 1988, one third of the fatalities occurred after the first 6 months of therapy as compared with 6% in the 1988 series. Clinical symptoms and laboratory findings were the same in patients with reversible and with fatal outcome. Early or immediate withdrawal of VPA after the first signs of VPA‐associated hepatotoxicity may be responsible for the increased number of children who recovered after VPA‐related severe liver failure. The pathogenesis of liver failure during VPA treatment remains unknown; metabolic defects and cofactors such as polypharmacy or infections have become increasingly likely to contribute by depleting intracellular CoA. Worldwide, 132 patients have died of VPA‐associated liver failure and/or pancreatitis. Because a group at risk for fatalities with VPA cannot be defined precisely, patients treated with VPA and their families must be made well aware of the clinical symptoms of hepatotoxicity such as apathy, vomiting, or increased seizure frequency, especially in the presence of febrile infections. Laboratory tests and clinical controls during the first 6 months of therapy should not be neglected.
Effect of Glycine on Valproate Toxicity in Rat Hepatocytes
Authors: Vance Michael A. , Gray Phillip D. , Tolman Keith G.
Published: October 2005

Summary: The interaction between the amino acid glycine and valproate (VPA), an antiepileptic drug (AED) that occasionally causes hepatotoxicity, was studied in rat hepatocytes in monolayer culture. Valproate caused a doseependent increase in leakage of lactic acid dehy‐drogenase (LDH), and glycine prevented this toxic response. L‐Carnitine, L‐lanine, and L‐cysteine did not protect hepatocytes from VPA. Glycine also partially antagonized inhibition of fatty acid β‐oxidation by VPA, as estimated by the generation of acid‐soluble products from [14C]palmitic acid. These results are consistent with the hypothesis that glycine prevents VPA toxicity by removing acyl‐CoA esters, which accumulate during VPA exposure and interfere with fatty acid p‐oxidation. Glycine, however, also antagonized the toxic effects of acetaminophen on hepatocytes, although at higher concentrations than required to protect hepatocytes from VPA. Because the mechanism of toxicity of acetaminophen probably is different from that of VPA, a nonspecific cytoprotective effect may contribute to glycine antagonism of valproate toxicity. Our results emphasize the importance of glycine in protecting hepatocytes from noxious insult in general as well as from VPA in particular.
Acute Cholangitis Induced by Carbamazepine
Authors: La Spina I. , Secchi P. , Grampa G. , Uccellini D. , Porazzi D.
Published: October 2005

Summary: We report a case of a patient with fever and intrahepatic cholestasis induced by carbamazepine (CBZ). This adverse reaction has been described in only a single case. We observed complete resolution of the hepatic damage once the agent was discontinued. CBZ rechallenge was followed by recurrence of all symptoms and abnormalities. Hepatic function improved again when CBZ was discontinued.
Correlations Between Magnetic Resonance Imaging‐Based Hippocampal Sclerosis and Depth Electrode Investigation in Epilepsy of the Mesiotemporal Lobe
Authors: Baulac Michel , Saint‐Hilaire J. M. , Adam C. , Martinez M. , Fontaine S. , Laplane D.
Published: October 2005

Summary: Quantitative analysis of hippocampal formations (HF) by magnetic resonance imaging (MRI) was correlated with depth electrode recordings in 18 patients with partial epilepsy. All had seizures of mesiotemporal origin. Electrodes explored three HF segments: amygdala and HF head and anterior and posterior HF body. Corresponding. HF measurements were made on coronal MRI sequences, and atrophy was quantified by one global and three segmental indexes of asymmetry per patient. HF from which seizure originated showed global atrophy in 15 patients. Segmental analysis demonstrated discrete tissue damage in 1 patient; thus, 16 patients (88%) had significant hippocampal atrophy ipsilateral to the mesial focus. The existence of more pronounced atrophy in segments giving rise to ictal onset than in segments without ictal onset was not statistically significant. Nevertheless, in posterior HF, all segments (four) with seizure onset were atrophied and none of the nonatrophied posterior segments (four) were at seizure origin. These findings confirm that MRI‐detected hippocampal atrophy is a powerful indicator of a mesiotemporal focus and strongly contributes to consideration of resective surgery without intracerebral EEG monitoring. Study of the distribution of maximal tissue damage may add some information, and help surgeons decide on the posterior extent of hippocampus removal. As illustrated by 3 patients who had multiple sites of seizure onset, however, the presence of this marker should not be interpreted systematically as evidence of pure mesiotemporal epilepsy.
Temporal and Spatial Characteristics of Intracerebral Seizure Propagation: Predictive Value in Surgery for Temporal Lobe Epilepsy
Authors: Adam Claude , Saint‐Hilaire Jean‐Marc , Richer Frangois
Published: October 2005

Summary: We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure‐free patients and 7 others who were almost seizure‐free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contra‐lateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays <1·0 s, but propagation times >1·0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.
Global Aphasia with Seizure Onset in the Dominant Basal Temporal Region
Authors: Abou‐Khalil Bassel , Welch Larry , Blumenkopf Bennett , Newman Karen , Whetsell William O.
Published: October 2005

Summary: A 33‐year‐old right‐handed woman had intractable simple and complex partial seizures (SPS, CPS) that began with global aphasia. EEG closed‐circuit TV (EEG‐CCTV) monitoring with sphenoidal electrodes showed left inferomesial temporal ictal onset of CPS. Subdural electrodes were implanted over the left frontotemporal convexity, sub temporally and subfrontally. Stimulation of the basotemporal cortex produced global aphasia. A posterolaterotemporal language area was also identified. Spontaneous SPS had focal onset in the basal temporal language area (BTLA). Ictal discharges did not involve the posterotemporal region. This case shows that aphasic speech arrest at seizure onset may be due to seizure discharge in the basotemporal region and that the BTLA is clinically relevant in seizure semiology.
Extratemporal Cortical Resections and Lesionectomies for Partial Epilepsy: Complications of Surgical Treatment
Authors: Cascino Gregory D. , Sharbrough Frank W. , Trenerry Max R. , Marsh W. Richard , Kelly Patrick J. , So Elson
Published: October 2005

Summary: Fifty patients with medically refractory extratemporal seizures underwent epilepsy surgery at our institution between 1988 and 1992. Twenty‐nine patients (group 1) had an extratemporal (mainly frontal lobe) corticectomy, and 21 patients (group 11) had an epileptogenic lesion extirpated without resection of the epileptic brain tissue. Comprehensive neurologic evaluation was performed preoperatively, soon after operation, and ∼3 months postoperatively to assess operative outcome. Magnetic resonance imaging (MRI) in group I patients usually showed no abnormality or a large destructive lesion. Neuroimaging showed a foreign tissue lesion in most group II patients. Thirteen of the 29 patients who underwent corticectomy had at least one adverse event (AE) potentially related to operation at the time of initial assessment. Four of the 13 patients required a surgical procedure to treat the operative complication, but only 1 of the 13 patients had a persistent neurologic deficit at follow‐up examination. Three of the 21 patients who received lesionectomy had acute and persistent neurologic morbidity. Patients undergoing cortical resection remained intubated longer postoperatively (p < 0·005), and required longer hospitalization after operation (p < 0·001) and in the intensive care unit (p < 0·001) as compared with the lesionectomy group. Results of this study may prove useful in counseling patients regarding neurologic outcome after extratemporal surgery.
Attention Problems in Epilepsy: Possible Significance of the Epileptogenic Focus
Authors: Piccirilli Massimo , D'Alessandro Patrizia , Sciarma Tiziana , Cantoni Cristina , Dioguardi Maria Stefania , Giuglietti Marta , Ibba Anna , Tiacci Carnillo
Published: October 2005

Summary: Investigation of the relation between epilepsy and cognition presents serious methodologic problems because several factors may contribute to impair neuropsychological performances in epileptic persons. Benign epilepsy of childhood with rolandic paroxysmal discharges (EPR) may be a very useful model of investigation in relation to opportunity to examine subjects without brain damage, therapy, and negative environmental influences. Thus, neuropsychological dysfunction in patients with EPR may support the hypothesis that epilepsy itself plays a specific role in the genesis of cognitive disturbances. We assessed the impact of the laterality of the epileptogenic focus on cognition of children with EPR. All subjects performed a figure cancellation task, a test used to evaluate mainly attention mechanisms and abilities in processing visuospatial information. Results showed that children with right‐sided (or bilateral) focus scored worse, whereas children with left‐sided focus performed as well as the control subjects. Our data agree with those of studies suggesting that focal discharges may be related to poor cognitive performance. Evidence of a concordance between neurophysiologic and neuropsy‐chologic findings may have great practical and theoretical implications in management of epileptic patients.
Epilepsy with Electrical Status Epilepticus During Slow Sleep and Secondary Bilateral Synchrony
Authors: Kobayashi Katsuhiro , Nishibayashi Naohiro , Ohtsuka Yoko , Oka Eiji , Ohtahara Shunsuke
Published: October 2005

Summary: In 3 children with “epilepsy with electrical status epilepticus during slow sleep” (ESES), we estimated interhemispheric small time differences (TDs) during spike‐wave activity in EEG by coherence and phase analysis by the two‐dimensional autoregressive model to differentiate their continuous diffuse spike‐waves during slow‐wave sleep (CSWS) between primary bilateral synchrony and secondary bilateral synchrony (SBS). Maximal TDs at onset of apparently bilateral synchronous spike‐wave bursts (BSSWs) during slow‐wave sleep were 12·0–26·5 ms (mean 20·3 ms) with consistent leading hemispheres in eight bursts of the 3 patients, indicating SBS as pathophysiology of their CSWS. This suggestion was supported by their clinico‐EEG findings, including the effect of a single oral dose of clobazam (CLB) on EEG. Three ictal BSSWs of atypical absence seizures in 2 patients were also analyzed to obtain maximal TDs of 17·9–41·7 ms (mean 26·3 ms) at onset, with the same leading sides as in sleep, also indicating SBS. Examination of intraburst TD variations showed no consistent disappearance of TDs during the latter part of the bursts, in either sleep or the ictal EEGs of atypical absences, and a role of the corpus callosum was suggested in the generation of SBS in ESES.
Generalized Convulsive Status Epilepticus: Causes, Therapy, and Outcome in 346 Patients
Authors: Scholtes Frans B. , Renier Willy O. , Meinardi Harry
Published: October 2005

Summary: We report data from 346 admissions for generalized tonic‐clonic convulsive status epilepticus (GC‐SE); 68% had had epilepsy previously. Outcome was determined by underlying cause, SE duration of <4 h, the presence of more than one medical complication, and the quality of therapy and management. Clonazepam (CZP), diazepam (DZP), and phenytoin (PHT) were most frequently used for treatment.
Influence of Epilepsy and Temporal Lobe Resection on Olfactory Function
Authors: West Steven E. , Doty Richard L.
Published: October 2005

Summary: Olfactory auras accompany some cases of epilepsy. Several aspects of olfactory function, including sensitivity, also may be altered. We reviewed the literature on these topics, as well as studies evaluating the influences of temporal lobe resection and other seizure management procedures on olfactory function. We concluded that: (a) despite several studies, the prevalence of olfactory auras in epilepsy is unknown, with estimates ranging from <1% to >30%; (b) epilepsy appears to cause a generalized decrease in olfactory functioning, although increased sensitivity may occur in some epileptic patients at some time in the preictal period; (c) other sensory modalities are also affected by the epileptic process which, in some cases, involve limbic‐related temporal lobe structures; (d) many of the olfactory deficits previously attrib‐uted to temporal lobe resection actually exist preoperatively; (e) a tastehlavor confusion exists in the reporting of taste auras; (0 unpleasant auras are associated with hyperresponsiveness of neurons, which may explain why most epilepsy‐related olfactory auras are described as “bad”; and (g) interesting parallels exist between the effects of the neuroendocrine system on seizure activity and olfactory function.
Physiologic and Morphologic Characteristics of Granule Cell Circuitry in Human Epileptic Hippocampus
Authors: Franck JoAnn E. , Pokorny Jaroslav , Kunkel Dennis D. , Schwartzkroin Philip A.
Published: October 2005

Summary: Morphological and electrophysiological techiques were used to examine granule cells and their mossy fiber axons in nine surgically resected hippocampal specimens from temporal lobe epilepsy (TLE) patients. Timm histochemistry showed mossy fiber sprouting into the inner molecular layer (IML) of the dentate in a subset of tissue samples. In slices from five tissue samples, stimulus‐induced bursting activity could be induced with a low concentration (2.5 μM) of bicuculline; bursts were sensitive to the N‐methyl‐d‐aspartate (NMDA) blocker, APV. There was a general correlation between such sprouting and experimentally induced yperexcit ability. Fourteen granule cells from five tissue samples were intracellularly stained [with lucifer yellow (LY) or neurobiotin]. Axons from a subset of these neurons showed axon collaterals reaching into the IML, but this axon projection pattern for single cells was not directly correlated with degree of mossy fiber sprouting shown grossly by Timm staining. Electron microscopic examination of intracellularly stained elements showed mossy fiber axon terminals making asymmetric synaptic contacts (including autapses on the granule cell dendrite) with dendritic shafts and spines in both apical and basal domains. These data are consistent with the hypothesis that mossy fiber sprouting provides a structural basis for recurrent excitation of granule cells, but does not provide direct support of the hypothesis that mossy fiber sprouting causes hyperexcitability. The data suggest that granule cell bursting activity is at least in part a function of compromised synaptic inhibition, since levels of γ‐aminobutyric acid (GABA) blockade that are generally subthreshold for burst induction were epileptogenic in some tissue samples from human epileptic hippocampus.
Comparative Anticonvulsant Activity and Neurotoxicity of 4–Amino‐N‐(2,6‐Dimethylphenyl)Phthalimide and Prototype Antiepileptic Drugs in Mice and Rats
Authors: Bailleux Vincent , Vallée Louis , Nuyts Jean‐Pierre , Hamoir Gaëtane , Poupaert Jacques H. , Stables James P. , Vamecq Joseph
Published: October 2005

Summary: We compared the anticonvulsant activity and neurotoxicity of 4‐amino‐N‐(2,6–dimethyl‐phenyl)phthalimide (ADD213063)with those of phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), ethosuximide (ESM), valproate (VPA), and felbamate (FBM). Evaluation of anticonvulsant properties performed according to well‐established procedures in rats and mice showed that ADD 213063 is most effective in protecting animals against maximal electroshock seizures (MES). This anti‐MES activity is achieved with nontoxic doses, with the optimal effect recorded in rats dosed orally with anti‐MES ED, and protective index (PI) values of 25.2 FmoYkg and >75, respectively. ADD 213063 protects to a lesser extent against seizures induced by subcutaneous (s.c.) picrotoxin and subcutaneous pentylenetetrazol(FTZ) in mice dosed intraperitoneally and orally, respectively. The profile of anticonvulsant action of ADD 213063 closely parallels that of CBZ.
Anticonvulsant Efficacy of ADCI (5‐Aminocarbonyl‐10, 11‐dihydro‐5H‐dibenzo[a, d] cyclohepten‐5,10‐imine) After Acute and Chronic Dosing in Mice
Authors: Rogawski Michael A. , Le Dung Q. , Uyakul Duangchan , Pannell Lewis K. , Subramaniam Swaminathan , Yamaguchi Shun‐ichi , Kokate Tushar G.
Published: October 2005

Summary: ADCI (5‐aminocarbonyl‐10, 11‐dihydro‐5H‐dibenzo[a, d] cyclohepten‐5,10‐imine), a low‐affinity uncompetitive N‐methyl‐d‐aspartate (NMDA) antagonist, is a broad‐spectrum anticonvulsant with a favorable side‐effect profile. In the present study, we sought to determine if tolerance develops to the anticonvulsant activity of ADCI, using the maximal electroshock (MES) test to assess seizure protection. Mice were treated with three daily injections of a 2 × ED50, dose for MES protection (18 mg/kg, intraperitoneally, i.p.) or vehicle for 7 or 14 days. On the day after the chronic treatment protocol, all animals received a challenge dose of ADCI (18 mg/kg) and 15 min later were evaluated in the MES test. In control animals, 83–94% of animals were protected and the ADCI plasma levels immediately after the MES test were 5.5–9.7 μg/ml. In treated animals, 29 and 0% of animals were protected at 7 and 14 days, respectively, and the ADCI plasma levels were 77 and 52% of the control values. [3H]Dizocilpine binding to brain NMDA receptors was unaltered by the chronic drug treatment. In subsequent experiments, we determined that 14‐day chronically treated animals could be completely protected by increased doses of ADCI (ED50, 28.9 mg/kg). In both native and chronically treated animals receiving a challenge dose of ADCI, plasma drug levels decreased in two phases, the first with a time constant of ∼55 min and the second with a much slower rate. The estimated plasma concentrations of ADCI reflecting threshold (3–5 pg/ml) and 50% protection (5–7.5 μg/mg) were similar in naive and chronic animals. We conclude that tolerance to ADCI is due to pharmacokinetic factors (enhanced first‐pass metabolism) and does not result from a reduction in anticonvulsant efficacy.
Induction of Pseudoseizures with Intravenous Saline Placebo
Authors: Slater Jeremy D. , Brown Marland C. , Jacobs William , Ramsay R. Eugene
Published: October 2005

Summary: For a 2‐year period, all patients admitted to the inpatient adult EEG videotelemetry unit of the University of Miami School of Medicine underwent attempted event induction with intravenous normal saline placebo. Of 175 patients monitored during that period, 101 underwent attempted placebo saline induction, whereas 58 patients were either in the pediatric age group, were undergoing a repeat hospitalization (i.e., depth electrode monitoring), or refused induction. The final diagnosis in each patient was established after re‐view of the history; physical, interictal, and ictal EEG findings; brain imaging studies; interictal and postictal brain single photon emission computed tomography (SPECT) and serum prolactin levels; psychiatric and psychological evaluations; and detailed neuropsychological testing. Final diagnoses were separated into epilepsy alone, pseudoseizures, epilepsy and pseudoseizures, and other (neither epilepsy nor pseudoseizures). No patient with an eventual diagnosis of epilepsy alone was inducible. Forty‐one patients with a diagnosis of epilepsy were not inducible. Of 32 patients with an eventual diagnosis of pseudoseizures, 29 were inducible. One of these 29 was also diagnosed with epilepsy. Three patients with aneventual diagnosis of pseudoseizures were not inducible; 90.6% of patients with an eventual diagnosis of pseudoseizures were inducible, i.e., had events identical to those reported by history, after injection of saline placebo. Placebo saline injection is a safe and effective means of distinguishing epilepsy from pseudoseizures.
Self‐Injury and Incontinence in Psychogenic Seizures
Authors: Peguero Edwin , Abou‐Khalil Bassel , Fakhoury Toufic , Mathews George
Published: October 2005

Summary: Two patients who incurred significant injuries during psychogenic seizures prompted us to do a telephone survey of self‐injury and incontinence in 102 consecutive patients diagnosed with psychogenic seizures by EEG‐closed‐circuit TV (EEG‐CCTV) monitoring. Seventy‐three patients (or a close family member or friend) were reached by telephone and responded to our survey. During typical attacks of psychogenic seizures, 40% reported injuries, 44% reporting tongue biting, and 44% reported urinary incontinence. Suicide attempts were reported by 32% and were more common in those with self‐injury and urinary incontinence. We compared the results of patients with psychogenic seizures with those of 30 patients with refractory epilepsy documented by ictal recordings, using a similar telephone survey. Injuries of all types were more commonly reported by epilepsy patients. Burn injuries were reported only by patients with epilepsy. Suicide attempts were more commonly reported by the psychogenic seizure group. Self‐injury and incontinence are commonly reported by psychogenic seizure patients. In view of their significant association with suicide attempts, they may indicate an underlying depression.
Benzodiazepine‐GABAA Receptor Binding During Absence Seizures
Authors: Prevett Martin C. , Lammertsma Adriaan A. , Brooks David J. , Cunningham Vincent J. , Fish David R. , Duncan John S.
Published: October 2005

Summary: The role of benzodiazepine (BZD)‐γ‐aminobutyric acid, (GABA) receptors in the pathogenesis of absence seizures is uncertain. In this study, we examined the effect of absence seizures on the binding of flumazenil to the BZD binding site of the GABA, receptor. Five patients with idiopathic generalized epilepsy (IGE) were studied at rest and during absence seizures with [11C]flumazenil and positron emission tomography (PET). Normalized regional cerebral time‐activity curves from the resting and ictal scans were compared with each other and with computed simulations showing the effects of changes in cerebral blood flow (CBF) and [11Clfluma‐zenil binding. No evidence was found for a change in [11C]flumazenil binding with absence seizures. This result, together with those of a recent study showing no abnormality of [11C]flumazenil binding interictally in patients with childhood and juvenile absence epilepsy (JAE) does not support a primary role for the BZD binding site of the GABA, receptor in the pathogenesis of absence seizures.
Pharmacokinetics of Tiagabine, a γ‐Aminobutyric Acid‐Uptake Inhibitor, in Healthy Subjects After Single and Multiple Doses
Authors: Gustavson Linda E. , Mengel Helle B.
Published: October 2005

Summary: Tiagabine (TGB) HC1, a new antiepilepticcompound, is a potent and specific inhibitor of γ‐aminobutyric acid (GABA) uptake. In conjunction with threephase I studies, the pharmacokinetics of TGB were examined in 58 healthy male volunteers. Study I involvedsingle increasing doses (2–24 mg TGB HC1); study II involved doses of 2–10 mg given once daily for 5 days;study III explored one dose daily (6 or 12 mg) for 14consecutive days. Plasma TGB concentrations were measured by high‐performance liquid chromatography(HPLC). Pharmacokineticprofiles were similar in all three studies and indicated thatthe processes of absorption and elimination of TGB werelinear. The drug was rapidly absorbed, and half‐life (tV2)averaged 5–8 h. The accumulation ratio was fairly low:1.4 in most subjects. Secondary peaks in plasma concentration‐time profiles suggested enterohepatic recycling. Lack of significant effects on antipyrine clearanceindicated that TGB does not induce or inhibit hepaticmicrosomal enzyme systems.
A Review of the Preclinical Pharmacology of Tiagabine: A Potent and Selective Anticonvulsant GABA Uptake Inhibitor
Authors: Suzdak Peter D. , Jansen Jens Aas
Published: October 2005

Summary: We review the neurochemical and behavioral profile of the selective γ‐aminobutyric acid (GABA) up‐take inhibitor, (R)‐N‐(4,4‐di‐(3‐methylthien‐2‐yl)but‐3‐enyl) nipecotic acid hydrochloride [tiagabine (TGB), previously termed NNC 05‐0328, NO 05‐0328, and NO‐328], which is currently in phase III clinical trials for epilepsy. TGB is a potent, and specific GABA uptake inhibitor. TGB lacks significant affinity for other neurotransmitter receptor binding sites and/or uptake sites. In electrophysiological experiments in hippocampal slices in culture, TGB prolonged the inhibitory postsynaptic potentials (IPSP) and inhibitory postsynaptic currents (IPSC) in the CA1 and CA3 produced by the addition of exogenous GABA. In vivo microdialysis shows that TGB also in‐creases extracellular GABA overflow in a dose‐dependent manner. Together these biochemical data suggest that the in vitro and in vivo mechanism of action of TGB is to inhibit GABA uptake specifically, resulting in an increase in GABAergic mediated inhibition in the brain. TGB is a potent anticonvulsant agent against methyl‐6,7‐dimethyox‐4‐ethyl‐B‐carboline‐3‐carboxylate (DMCM)‐induced clonic convulsions (mice), subcutaneous pentylenetetrazol (PTZ)‐induced tonic convulsions (mice and rats), sound‐induced convulsions in DBA/2 mice and genetically epilepsy‐prone rats (GEPR), and electrically induced convulsions in kindled rats. TGB is partially efficacious against subcutaneous PTZ‐induced clonic convulsions, and photically induced myoclonus in Papio papio. TGB is weakly efficacious in the intravenous PTZ seizure threshold test and the maximal electroshock seizure (MES) test and produces only partial protection against bicuculline (BIC)‐induced convulsions in rats. The overall biochemical and anticonvulsant profile of TGB suggests potential utility in the treatment of chronic seizure disorders such as generalized clonic‐tonic epilepsy (GTCS), photomyoclonic seizures, myoclonic petit mal epilepsy, and complex partial epilepsy.