bluuebunny/crossref_metadata_2025 huggingface dataset:
Interictal and Ictal Magnetoencephalographic Study in Patients with Medial Frontal Lobe Epilepsy
Authors: Shiraishi Hideaki , Watanabe Yutaka , Watanabe Masako , Inoue Yushi , Fujiwara Tateki , Yagi Kazuichi
Published: March 2003

Summary:  Purpose: To determine whether magnetoencephalography (MEG) has any clinical value for the analysis of seizure discharges in patients with medial frontal lobe epilepsy (FLE).

Methods: Four patients were studied with 74‐channel MEG. Interictal and ictal electroencephalographic (EEG) and MEG recordings were obtained. The equivalent current dipoles (ECDs) of the MEG spikes were calculated.

Results: In two patients with postural seizures, interictal EEG spikes occurred at Cz or Fz. The ECDs of interictal MEG spikes were localized around the supplementary motor area. In the other two patients with focal motor or oculomotor seizures, interictal EEG spikes occurred at Fz or Cz. The ECDs of interictal MEG spikes were localized at the top of the medial frontal region. The ECDs detected at MEG ictal onset were also localized in the same area as those of the interictal discharges.

Conclusions: In medial FLE patients, interictal and ictal MEG indicated consistent ECD localization that corresponded to the semiology of clinical seizures. Our findings demonstrate that MEG is a useful tool for detecting epileptogenic focus.
Left Vagus Nerve Stimulation with the Neurocybernetic Prosthesis Has Complex Effects on Heart Rate and on Its Variability in Humans
Authors: Frei Mark G. , Osorio Ivan
Published: March 2003

Summary:  Purpose: The purpose of this study was to determine if stimulation of the left vagus nerve (LVNS) with the neurocybernetic prosthesis (NCP) in humans is, as claimed in the literature, without cardiac chronotropic actions.

Methods: We analyzed 228 h of ECG recorded from five subjects with intractable epilepsy who had not benefited from LVNS, for effects on instantaneous heart rate (IHR) and heart rate variability (HRV).

Results: There were two main cardiac responses: (a) bradycardia, and (b) tachycardia during the first half, followed by bradycardia during the second half of stimulation (biphasic response). Multiphasic responses characterized by alternating bradycardia and tachycardia were rarely observed. HRV was either increased or decreased depending on the subject and on the stimulation parameters. HRV as a function of HR also showed high interindividual variability, and interestingly, in one case behaved paradoxically, increasing at higher and decreasing at lower heart rates.

Conclusions: LVNS at high intensities has complex effects on IHR and HRV, which show large interindividual variability. These spectra of cardiac responses reflect the interplay of autonomic, visceral, and somatic sensory afferences and the role of central structures in their integration. These findings also point to the need for more comprehensive studies of cardiac function in humans implanted with the NCP, using sensitive methods for data processing and analysis such as those developed for this study.
Polycystic Ovarian Syndrome in Women with Epilepsy: A Review
Authors: Duncan Susan
Published: March 2003

Summary: Polycystic ovarian syndrome (PCOS) remains a controversial issue in women with epilepsy. The syndrome is characterized by clinical signs of endocrine dysfunction, such as irregular menstruation, hirsutism, and infertility, but its pathogenesis and presentation are heterogeneous. There are few data on the relationship between epilepsy and PCOS. Studies by a Finnish group have raised the issue of an association between valproate (VPA) and PCOS in young women with epilepsy. These studies, however, were retrospective, laid emphasis on polycystic ovary morphology rather than on clinical endocrine dysfunction, and were undertaken in selected populations. Further studies, both in Italy and Germany, failed to replicate the findings of the Finnish group. Future research should ideally be prospective and include baseline data in untreated women. No compelling data lead to a specific contraindication of the use of VPA in young women, and the drug remains a first‐line treatment option.
Effectiveness of First Antiepileptic Drug
Authors: Kwan Patrick , Brodie Martin J.
Published: March 2003

Summary:  Purpose: To investigate the interaction among efficacy, tolerability, and overall effectiveness of the first antiepileptic drug (AED) in patients with newly diagnosed epilepsy.

Methods: The 470 patients were diagnosed, treated and followed up from January 1984 at a single center. Outcome was classified as seizure freedom for at least the last year or failure of initial treatment because of inadequate seizure control, adverse events, or for other reasons.

Results: Overall, 47% of patients became seizure‐free with the first prescribed AED. A higher proportion (p = 0.025) of patients with symptomatic or cryptogenic epilepsy changed treatment because of intolerable side effects (17%), and a lower proportion (p = 0.007) became seizure‐free (43.5%) compared with those with idiopathic epilepsy (8.5% and 58%, respectively). Most patients (83%) received carbamazepine (CBZ; n = 212), sodium valproate (VPA; n = 101), or lamotrigine (LTG; n = 78). The majority of seizure‐free patients required only a moderate daily AED dose (93.1% with ≤800 mg CBZ, 91.3% with ≤1,500 mg VPA, 93.8% with ≤300 mg LTG), with commonest dose ranges being 400–600 mg for CBZ, 600–1,000 mg for VPA, and 125–200 mg for LTG. Most withdrawals due to poor tolerability also occurred at or below these dose levels (CBZ: 98%; VPA: 100%; LTG: 75%). Patients taking CBZ (27%) had a higher incidence of adverse events necessitating a change of treatment than did those treated with VPA (13%) or LTG (10%), resulting in fewer becoming seizure‐free (CBZ vs. VPA, p = 0.02; CBZ vs. LTG, p = 0.002).

Conclusions: Nearly 50% of newly diagnosed patients became seizure‐free on the first‐ever AED, with >90% doing so at moderate or even modest dosing. Tolerability was as important as efficacy in determining overall effectiveness.
Acute Psychosis During Intracranial EEG Monitoring: Close Relationship Between Psychotic Symptoms and Discharges in Amygdala
Authors: Takeda Youji , Inoue Yushi , Tottori Takayasu , Mihara Tadahiro
Published: March 2003

Summary:  Purpose: This report examined the underlying mechanism of psychosis associated with epilepsy.

Methods: An adult patient with epilepsy manifesting acute psychosis during long‐term EEG monitoring is presented, together with a literature review on this subject.

Results: A 25‐year‐old woman with intractable temporal lobe epilepsy developed acute psychosis while she underwent long‐term intracranial EEG monitoring. After a clustering of seizures, she manifested psychotic symptoms including hallucination, stupor, and repeated fear. The transition of psychotic symptoms corresponded to the changes in frequency and morphology of seizure discharges restricted to the left amygdala. Improvement of psychosis coincided with disappearance of seizure discharges.

Conclusions: This case confirmed a close relationship between psychotic symptoms and seizure discharges in the left amygdala. It is suggested that paroxysmal bombardment of the medial temporal lobe structure may be a pathogenetic factor of acute psychosis associated with epilepsy.
Secondarily Generalized Seizures in Mesial Temporal Epilepsy: Clinical Characteristics, Lateralizing Signs, and Association With Sleep–Wake Cycle
Authors: Jobst Barbara C. , Williamson Peter D. , Neuschwander Timothy B. , Darcey Terrance M. , Thadani Vijay M. , Roberts David W.
Published: March 2003

Summary:  Purpose: Secondarily generalized seizures (SGSs) are often considered to be stereotyped, presumably sharing a common electrical pathway. We examined whether SGSs are uniform in a homogeneous group of patients with mesial temporal epilepsy, and whether certain clinical signs associated with generalization are lateralizing with regard to seizure origin.

Methods: A comprehensive, standardized video/EEG analysis was performed of the clinical characteristics of 29 patients (69 SGSs) with mesial temporal seizure onset.

Results: The sequence of tonic postures, as well as the sequence of tonic and clonic activity, was variable in SGSs of mesial temporal origin. The sequence of tonic activity, followed by vibratory and then clonic activity alone, was seen only in 51.7% of patients. Tonic and clonic activity could occur simultaneously. The most common clinical signs were forced head deviation (89.7%) and vocalization (75.9%). The most common tonic posture was bilateral arm extension (72.4%). All other clinical signs occurred in <60% of patients. Among these, early forced head deviation, asymmetric tonic facial contraction, tonic arm abduction with elbow flexion, and tonic arm extension combined with opposite arm flexion had lateralizing significance. The preceding partial seizure in SGSs (mean, 43.6 s) was significantly shorter than partial seizures without generalization (mean, 105.2 s; p < 0.001). SGSs occurred more often out of sleep (p < 0.01).

Conclusion: Secondarily generalized seizures of mesial temporal origin are not uniform in their clinical presentation. The final phases of SGSs are more stereotyped than the initial clinical signs of generalization. This suggests variable electrical spread patterns, which may end in a common pathway. Some asymmetric motor signs have lateralizing significance. SGSs were associated with sleep and abbreviated partial seizures.
Enhanced Calcium Influx in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats
Authors: Amano Hiroko , Amano Taku , Matsubayashi Hiroaki , Ishihara Kumatoshi , Serikawa Tadao , Sasa Masashi
Published: March 2003

Summary:  Purpose: The spontaneously epileptic rat (SER: tm/tm, zi/zi) shows both absence‐like seizures and tonic convulsions. Our previous electrophysiologic studies have demonstrated that SER has abnormal excitability of hippocampal CA3 neurons, which shows a long‐lasting depolarization shift by a single stimulation of mossy fibers, probably resulting from the Ca2+ channel abnormalities. The present study was performed to determine whether Ca2+ influx is actually enhanced in the CA3 area of SER.

Methods: Hippocampal slices were prepared from normal Wistar rats and SER aged 11–16 weeks old, when the epileptic seizures had been observed, and loaded with fura‐2AM. Intracellular Ca2+ concentration ([Ca2+]i) was monitored as the ratio of fluorescence intensities excited at wavelengths of 340 and 380 nm (RF340/F380) with photometric devices.

Results: High K+ (10∼60 mM) applied to the bath for 2 min increased [Ca2+]i in hippocampal CA1, CA3, and dentate gyrus (DG) areas of both the normal rats and SER in a concentration‐dependent manner. However, the high K+–induced increase in [Ca2+]i was significantly more pronounced in the CA3 area of the SER than in that of the normal animals, whereas there were no significant differences in high K+–induced increases of [Ca2+]i in CA1 or DG between the SER and controls. The high K+–induced increases in [Ca2+]i of CA1, CA3, and DG were inhibited by nifedipine (1∼10 nM), a Ca2+ channel antagonist in both SER and controls. However, the inhibition of the high K+–induced increase in [Ca2+]i by nifedipine (1 nM) was significantly greater in the CA3 area of SER than that of controls.

Conclusions: These findings suggest that Ca2+ influx through the L‐type Ca2+ channels is much greater in the CA3 area of SER than in that of normal animals and is involved in the epileptic seizures of the SER.
Topiramate Rapidly Raises Brain GABA in Epilepsy Patients
Authors: Petroff Ognen A. C. , Hyder Fahmeed , Rothman Douglas L. , Mattson Richard H.
Published: March 2003

Summary:  Purpose: The short‐ and long‐term pharmacodynamic effects of topiramate (TPM) on brain γ‐aminobutyric acid (GABA) metabolism were studied in patients with complex partial seizures.

Methods: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14‐cc volume in the occipital cortex using 1H spectroscopy with a 2.1‐Tesla magnetic resonance spectrometer and an 8‐cm surface coil. Fifteen patients (four men) were studied serially after the first, oral dose (100 mg) of TPM.

Results: The first dose of TPM increased brain GABA within 1 h. Within 4 h, GABA was increased by 0.9 mM (95% CI, 0.7–1.1). Brain GABA remained elevated for ≥24 h. Pyrrolidinone and homocarnosine increased slowly during the first day. Daily TPM therapy (median, 300 mg; range, 200–500) increased GABA (0.3 mM; 95% CI, 0.1–0.5), homocarnosine (0.4 mM; 95% CI, 0.3–0.5), and pyrrolidinone (0.15 mM; 95% CI, 0.10–0.19), compared with levels before TPM. There was no dose response evident with daily TPM doses of 200–500 mg.

Conclusions: TPM promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the effects of increased homocarnosine and pyrrolidinone within 24 h.
Outcome of Severe Refractory Status Epilepticus in Children
Authors: Sahin Mustafa , Menache Caroline C. , Holmes Gregory L. , Riviello James J.
Published: March 2003

Summary:  Purpose: Refractory status epilepticus (RSE) is the persistence of seizure activity despite appropriate therapy; it is treated with high‐dose suppressive anesthetic agents. We report here the outcome of RSE in a large series of children.

Methods: We retrospectively reviewed cases of RSE treated at Children's Hospital, Boston, between 1992 and 2000. Factors evaluated included age, history of seizures or neurologic impairment, etiology, outcome, including mortality or return to baseline, and initial EEG findings.

Results: Twenty‐two patients ages 4.5 months to 18 years were admitted to the intensive care unit for RSE. All were treated with high‐dose suppressive therapy consisting of pentobarbital, midazolam, propofol infusion, or high‐dose phenobarbital, either alone, or in combination, for ≤146 days. The overall mortality was seven of 22. Mortality was related to etiology, age, and EEG findings. No death occurred in the remote symptomatic group, and three of four younger than 3 years died, whereas only four of 18 older than 3 years died. The mortality rate among patients with focal abnormalities on the EEG was lower than that among those with multifocal or generalized abnormalities. None of the children with normal premorbid neurologic status returned to baseline.

Conclusions: Our data demonstrate a high mortality and morbidity for childhood RSE. Mortality is related to etiology and is higher in younger children and with multifocal or generalized abnormalities on the initial EEG.
Incidence of Drug‐Induced Aggravation in Benign Epilepsy with Centrotemporal Spikes
Authors: Corda Davide , Gelisse Philippe , Genton Pierre , Dravet Charlotte , Baldy‐Moulinier Michel
Published: March 2003

Summary:  Purpose: Benign epilepsy with centrotemporal spikes (BECTS) is characterized by an excellent prognosis. Drug therapy is necessary in only a minority of patients. Carbamazepine (CBZ) and phenobarbital (PB) have been reported to cause electroclinical aggravation in some cases. The incidence of drug‐induced aggravation in BECTS has never been established.

Methods: We retrospectively studied 98 consecutive cases of BECTS, examined at the Centre Saint Paul between 1984 and 1999; 82 patients had received one or more treatments, often successively and in association.

Results: We found only one case of electroclinical aggravation with CBZ among 40 patients exposed to CBZ (35 in monotherapy, five in polytherapy). An additional case showed a marked EEG aggravation on CBZ + PB among 14 patients taking PB (nine with monotherapy and five with polytherapy), and PB was apparently responsible. No patient treated with valproate or benzodiazepines showed aggravation.

Conclusions: Aggravation of BECTS caused by antiepileptic drugs happens only rarely. There is a minor risk of aggravation with CBZ and also probably with PB. Drug‐induced aggravation may occur only during certain periods coinciding with spontaneous worsening of BECTS.
Seizures in the Critically Ill: The Role of Imipenem
Authors: Koppel Barbara S. , Hauser W. Allen , Politis Chrissoula , Van Duin David , Daras Michael
Published: March 2003

Summary:  Purpose: To determine the risk of seizures in critically ill patients receiving the antibiotic imipenem, a broad‐spectrum antibiotic that has been associated with seizures. Reports generally have not considered other contributing factors such as dose, seizure history, and morbidity index of the underlying illness necessitating the antibiotic.

Methods: Charts of all patients in a 450‐bed municipal hospital who received imipenem in a 6‐month period, as determined by pharmacy records, were reviewed for dosage and duration of imipenem use, occurrence of seizures. and mortality outcome. Attention was paid to demographic features; pattern of seizure occurrence during, before, and after imipenem use; renal function; and correction for dosage based on size.

Results: Seventy‐five charts were reviewed. Sixty‐three patients had no seizures during the hospitalization, four had seizures while receiving imipenem, and eight had seizures during the hospitalization but before or after imipenem use. The incidence of seizures was 4/1,000 patient‐days on, and 3.9/1,000 patient‐days off imipenem (not significant). The risk of seizure in both groups was considerably higher in those patients with a history of seizures before hospitalization. The presence of other factors that could contribute to increased concentration of imipenem in the brain, such as renal failure or acute stroke, did not contribute to seizure incidence. Metabolic derangement, anoxia, and phenytoin discontinuation did contribute to seizure incidence.

Conclusions: Seizure incidence is increased in all critically ill patients (16% of patients studied), but with no added risk during the period patients received imipenem. Determining the proper dose based on a patient's body mass, correction of dose in the presence of renal failure, and avoidance of excess of 2 g/day of imipenem removes any added risk for seizures from imipenem. Despite experimental data to suggest action of imipenem on the glutamate/N‐methyl‐d‐aspartate receptor, or interference with binding to the γ‐aminobutyric acid receptor, and early clinical studies that warned against its use because of seizure risk, we found that careful use of this antibiotic is safe.
Surgical Resection for Intractable Epilepsy in “Double Cortex” Syndrome Yields Inadequate Results
Authors: Bernasconi A. , Martinez V. , Rosa‐Neto P. , D'Agostino D. , Bernasconi N. , Berkovic S. , MacKay M. , Harvey A. Simon , Palmini A. , Da Costa J. Costa , Paglioli Eliseu , Kim H.I. , Connolly M. , Olivier A. , Dubeau F. , Andermann E. , Guerrini R. , Whisler W. , De Toledo‐Morrell L. , Morrell F. , Andermann F.
Published: March 2003

Summary:  Purpose: To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder.

Methods: We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video‐EEG recordings and magnetic resonance imaging (MRI).

Results: All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved.

Conclusion: Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.
Anticonvulsant Activity of N‐Palmitoylethanolamide, a Putative Endocannabinoid, in Mice
Authors: Lambert Didier M. , Vandevoorde Séverine , Diependaele Gérald , Govaerts Sophie J. , Robert Annie R.
Published: March 2003

Summary:  Purpose: The purpose of this study was to evaluate in mice the anticonvulsant potential of N‐palmitoylethanolamide, a putative endocannabinoid that accumulates in the body during inflammatory processes.

Methods: N‐palmitoylethanolamide was injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant activity [in maximal electroshock seizure (MES) and chemical‐induced convulsions] and for neurologic impairment (rotorod). It was compared with anandamide and with different palmitic acid analogues as well as with reference anticonvulsants (AEDs) injected under the same conditions.

Results: The MES test showed, after i.p. administration to mice, that N‐ palmitoylethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutaneous pentylenetetrazol test and in the 3‐mercaptropropionic acid test, it was effective only against tonic convulsions. N‐palmitoylethanolamide was devoid of neurologic impairment ≤250 mg/kg, yielding a high protective index.

Conclusions: N‐palmitoylethanolamide, an endogenous compound with antiinflammatory and analgesic activities, is a potent AED in mice. Its precise mechanism of action remains to be elucidated.
Late Seizure Recurrence after Multiple Subpial Transections
Authors: Orbach Darren , Romanelli Pantaleo , Devinsky Orrin , Doyle Werner
Published: March 2003

Summary: We studied long‐term outcome (range, 28–89 months; mean, 56 months) after multiple subpial transections (MST) for medically refractory epilepsy. Forty‐three (79.6%) of 54 patients had a consistent significant reduction in seizure frequency, and 27 (50%) of the 54 were either entirely seizure free or virtually so. However, 10 (18.5%) patients sustained an increase in seizure frequency several years after surgery, after showing initial postoperative improvement. This suggests that late seizure recurrence is a more important problem in cases in which MST has been performed than for pure resections.
The Effects of Lamotrigine on Sleep in Patients with Epilepsy
Authors: Foldvary Nancy , Perry Michael , Lee Julia , Dinner Dudley , Morris Harold H.
Published: March 2003

Summary:  Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in REM, slow‐wave sleep (SWS) and sleep latency, and increased percentage of light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of lamotrigine (LTG) on sleep.

Methods: Ten adults with focal epilepsy, in whom the decision was made to add LTG to either phenytoin (PHT) or carbamazepine (CBZ) for control of seizures, were the subjects of this study. Patients underwent pre‐ and posttreatment polysomnography (PSG) and completed sleep questionnaires. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon sign rank test.

Results: Seven patients were taking CBZ, and three were treated with PHT. All subjects were titrated to an LTG dose of 400 mg/day. Treatment with LTG produced a significant decrease in SWS and an increase in stage 2 sleep percentage. No significant difference in ESS or any of the other polygraphic variables was observed. However, LTG treatment was associated with a reduction in arousals and stage shifts and an increase in REM periods. No subjects reported insomnia with treatment.

Conclusions: LTG appears to be less disruptive to sleep than some of the older AEDs.
Validity of Three Measures of Health‐related Quality of Life in Children with Intractable Epilepsy
Authors: Sherman Elisabeth M. S. , Slick Daniel J. , Connolly Mary B. , Steinbok Paul , Camfield Carol , Eyrl Kim L. , Massey Cathy , Farrell Kevin
Published: March 2003

Summary:  Purpose: Validity studies on health‐related quality of life (HRQOL) scales for pediatric epilepsy are few, and cross‐validation with other samples has not been reported. This study was designed to assess the validity of three parent‐rated measures of HRQOL in pediatric epilepsy: (a) the Impact of Childhood Illness Scale (ICI), (b) the Impact of Child Neurologic Handicap Scale (ICNH), and (c) the Hague Restrictions in Epilepsy Scale (HARCES).

Methods: Retrospective data were examined for 44 children with intractable epilepsy. Validity was assessed by evaluating differences across epilepsy severity groups as well as correlations between HRQOL scales and neurologic variables (seizure severity, epilepsy duration, current/prior antiepileptic medications) and psychosocial measures (emotional functioning, IQ, social skills, adaptive behavior). Scale overlap with a global QOL rating also was assessed.

Results: The HRQOL measures were moderately to highly intercorrelated. The scales differed in terms of their associations with criterion measures. The HARCES was related to the highest number of neurologic variables and the ICNH to the fewest. All three scales were related to psychosocial functioning and to global quality of life.

Conclusions: The results of this study suggest that the three measures are likely adequate measures of HRQOL for use in intractable childhood epilepsy. The measures were highly intercorrelated, and they were all broadly related to criterion measures reflecting specific domains of HRQOL as well as global QOL. Some differences between scales emerged, however, that suggest care in choosing HRQOL instruments for children with epilepsy.
Calcium‐dependent Epileptogenesis in an In Vitro Model of Stroke‐induced “Epilepsy”
Authors: Sun David A. , Sombati Sompong , Blair Robert E. , DeLorenzo Robert J.
Published: March 2003

Summary:  Purpose: Stroke is the most common cause of acquired epilepsy. The purpose of this investigation was to characterize the role of calcium in the in vitro, glutamate injury–induced epileptogenesis model of stoke‐induced epilepsy.

Methods: Fura‐2 calcium imaging and whole‐cell current clamp electrophysiology techniques were used to measure short‐term changes in neuronal free intracellular calcium concentration and long‐term alterations in neuronal excitability in response to epileptogenic glutamate injury (20 μM, 10 min) under various extracellular calcium conditions and in the presence of different glutamate‐receptor antagonists.

Results: Glutamate injury–induced epileptogenesis was associated with prolonged, reversible elevations of free intracellular calcium concentration during and immediately after injury and chronic hyperexcitability manifested as spontaneous recurrent epileptiform discharges for the remaining life of the cultures. Epileptogenic glutamate exposure performed in solutions containing low extracellular calcium, barium substituted for calcium, or N‐methyl‐d‐aspartate (NMDA)‐receptor antagonists reduced the duration of intracellular calcium elevation and inhibited epileptogenesis. Antagonism of non–NMDA‐receptor subtypes had no effect on glutamate injury–induced calcium changes or the induction epileptogenesis. The duration of the calcium elevation and the total calcium load statistically correlated with the development of epileptogenesis. Comparable elevations in neuronal calcium induced by non–glutamate receptor–mediated pathways did not cause epileptogenesis.

Conclusions: This investigation indicates that the glutamate injury–induced epileptogenesis model of stroke‐induced epilepsy is calcium dependent and requires NMDA‐receptor activation. Further, these experiments suggest that prolonged, reversible elevations in neuronal free intracellular calcium initiate the long‐term plasticity changes that underlie the development of injury‐induced epilepsy.
The Effectiveness of Cognitive Rehabilitation for Attention Deficits in Focal Seizures: A Randomized Controlled Study
Authors: Engelberts Nadine H. J. , Klein Martin , Adèr Herman J. , Heimans Jan J. , Trenité Dorothée G. A. Kasteleijn‐Nolst , Van der Ploeg Henk M.
Published: March 2003

Summary:  Purpose: Cognitive deficits are one of the major limiting factors in the everyday life functioning of patients with focal seizures. Although cognitive rehabilitation methods have been successfully applied to patients with other central nervous system (CNS) lesions, these methods have not yet been evaluated in cognitively impaired patients with epilepsy. The present study evaluated the effectiveness of two commonly used methods for attention deficits: (a) the Retraining Method, aimed at retraining impaired cognitive functions; and (b) the Compensation Method, aimed at teaching compensatory strategies while taking neuronal loss for granted.

Methods: Fifty adult outpatients with focal seizures and attention impairments receiving carbamazepine (CBZ) monotherapy were randomly assigned to the Retraining Method, the Compensation Method, or to a waiting‐list control group. Established and self‐reported neuropsychological outcomes and self‐reported quality of life of these groups were evaluated at pretraining, posttraining, and at a 6‐month follow‐up measurement point and were completed by 44 patients.

Results: Neuropsychological outcomes related to training, self‐reported neuropsychological outcomes, and quality of life at the 6‐month follow‐up measurement point improved both in the Retraining Method group (n = 19) and the Compensation Method group (n = 17) relative to the waiting‐list control group (n = 8). The Compensation Method was more effective in improving self‐reported neuropsychological outcomes and quality of life, especially for patients with less education. The patients with active epilepsy benefited more from both methods than did the seizure‐free patients.

Conclusions: These data show that cognitive rehabilitation programs are effective for patients with focal seizures and attention deficits and should, therefore, be incorporated into comprehensive care programs.
Expression of the Multidrug Transporter P‐glycoprotein in Brain Capillary Endothelial Cells and Brain Parenchyma of Amygdala‐kindled Rats
Authors: Seegers Ulrike , Potschka Heidrun , Löscher Wolfgang
Published: March 2003

Summary:  Purpose: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P‐glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala‐kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs.

Methods: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode‐implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti‐PGP antibody. Six brain regions were examined ipsi‐ and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum.

Results: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate‐treated rats were used as positive controls. As reported previously, kainate‐induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions.

Conclusions: Amygdala‐kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance–associated protein, might be involved in the resistance of kindled rats to AEDs.
Partial Epilepsy Manifesting Atonic Seizure: Report of Two Cases
Authors: Satow Takeshi , Ikeda Akio , Yamamoto Junichi , Takayama Motohiro , Matsuhashi Masao , Ohara Shinji , Matsumoto Riki , Begum Tahamina , Fukuyama Hidenao , Hashimoto Nobuo , Shibasaki Hiroshi
Published: March 2003

Summary:  Purpose: Atonic seizures are commonly seen in patients with generalized epilepsy but only infrequently in patients with partial epilepsy. Clinically generalized atonic seizures as a partial epilepsy have not been studied in detail with video/EEG monitoring. Here we describe the clinical and physiologic characteristics of atonic seizures due to partial epilepsy and discuss the underlying mechanism.

Methods: Two patients with partial epilepsy manifesting atonic seizures, one with frontal lobe epilepsy (FLE) and the other with parietal lobe epilepsy (PLE), were reported. The long‐term video/EEG monitoring, magnetic resonance imaging (MRI), and interictal fluorodeoxyglucose–positron emission tomography (FDG‐PET) were investigated in each patient.

Results: Paroxysmal diminution of muscle tone mainly involved the axial muscles in both patients. In contrast with the abrupt falls seen in patients with Lennox–Gastaut syndrome, the falls in these patients were slow, taking 2–5 s to fall down. Ictal EEG records showed low‐voltage fast activity in the frontocentral area followed by repetitive spikes at the midline frontocentral area in the patient with FLE, and rhythmic spikes in the left central area in the patient with PLE. Interictal FDG‐PET disclosed hypometabolic regions consistent with the clinical and EEG findings.

Conclusions: Slow falls might be a feature of atonic seizures in partial epilepsy. Long‐lasting atonia in partial epilepsy could be due to either one of the following two possible mechanisms: (a) epileptic activities arising from the negative motor area, of which 50‐Hz electric stimulation causes motor inhibition, or (b) sustained atonia with successive electromyogram (EMG) silent periods caused by epileptic discharges arising from the inhibitory area of the primary sensorimotor area.
Neural Networks Underlying Epileptic Humming
Authors: Bartolomei Fabrice , Wendling Fabrice , Vignal Jean‐Pierre , Chauvel Patrick , Liégeois‐Chauvel Catherine
Published: March 2003

Summary:  Purpose: Humming is a rare automatism occurring in partial seizures that has received little attention. Its study could shed light on the neural networks underlying melodic expression. In this study, we examined the anatomoelectroclinical correlates of humming during epileptic seizures

Methods: Three patients undergoing presurgical stereoelectroencephalography (SEEG) for medically intractable temporal lobe epilepsy were studied. Coherence analysis of SEEG activity was carried out to study the functional coupling of different regions of the brain, whereas time–frequency (TF) analysis was conducted to assess epileptic discharge patterns. Changes in coherence were studied to identify the neural structures/systems implicated in humming.

Results: Humming began after the onset of seizures generated in medial limbic regions of the temporal lobe. At seizure onset, coherence analysis showed an increase in amygdala–hippocampus coupling. Humming began after the onset of a rhythmic discharge over lateral regions of the superior temporal gyrus (STG). A highly significant increase in coherence was observed between prefrontal regions and the STG. TF analysis of the STG discharge showed a reproducible pattern with a single fundamental frequency and associated harmonics. This frequency was ∼6 Hz for two patients and 15 Hz for one patient.

Conclusions: These findings suggest that the occurrence of humming during epileptic seizures of the temporal lobe is associated with activity in a neural network involving the STG and the inferior frontal gyrus.
Effects of Fluoxetine and TFMPP on Spontaneous Seizures in Rats with Pilocarpine‐induced Epilepsy
Authors: Hernandez Eric J. , Williams Philip A. , Dudek F. Edward
Published: March 2003

Summary:  Purpose: Fluoxetine is a selective serotonin [5‐hydroxytryptamine (5‐HT)] reuptake inhibitor (SSRI) commonly used to treat depression. Some uncontrolled clinical studies have reported that SSRIs increase seizures, but animal experiments with evoked‐seizure models have suggested that SSRIs at therapeutic doses decrease seizure susceptibility. We tested the hypothesis that fluoxetine and trifluoromethylphenylpiperazine (TFMPP, a nonselective 5‐HT–receptor agonist) reduce the frequency of spontaneous motor seizures in pilocarpine‐treated rats.

Methods: Fluoxetine (20 mg/kg) and TFMPP (5 mg/kg) were administered to rats with pilocarpine‐induced epilepsy. Phenobarbital (PB; 10 mg/kg) was a positive control, and saline (i.e., 0.5 ml) controlled for the injection protocol. Each rat received each treatment (intraperitoneally) once per day for 5 consecutive days with 1 week between treatments. Rats were continuously video‐monitored for the last 72 h of each treatment.

Results: When compared with saline over the entire 72‐h observation period, PB and fluoxetine treatment, but not TFMPP, reduced the spontaneous‐seizure rate. Plots of magnitude of the drug effect as a function of seizure frequency after saline treatment revealed larger drug effects for fluoxetine and PB in the rats with the highest control seizure rate. When the data from the five rats with the highest seizure frequency in saline were analyzed for the first 6 h after treatment, TFMPP also significantly reduced seizure frequency.

Conclusions: Animal models with spontaneous seizures can be used to screen potential antiepileptic drugs, and fluoxetine and TFMPP reduce spontaneous seizures in the pilocarpine model of temporal lobe epilepsy.
Hippocampal Region Asymmetry Assessed by 1H‐MRS in Rolandic Epilepsy
Authors: Lundberg Staffan , Weis Jan , Eeg‐Olofsson Orvar , Raininko Raili
Published: March 2003

Summary:  Purpose: In a previous study, we reported hippocampal abnormalities on magnetic resonance imaging (MRI) in six of 18 children with rolandic epilepsy (RE). In this study, metabolic changes were analyzed in the hippocampal region with proton magnetic resonance spectroscopy (1H‐MRS).

Methods: In 13 children with electroclinically typical RE and 15 healthy controls, 1H‐MRS results of both hippocampal regions were analyzed. The voxels, 2 × 2 × 4‐cm each, were placed to include the head and body of the hippocampus. A PRESS sequence with TR 2,000 ms and TE 32 ms was used. Total N‐acetylaspartate (tNAA), glutamine and glutamate (Glx), and choline compounds (tCho) were related to total creatine (tCr), and asymmetry indices (AIs) were calculated. MRI was performed in all 13 patients and in 13 controls.

Results: The tNAA/tCr AI of the hippocampal region was significantly higher in children with RE than in control children (z = 4.49; p < 0.001). The AIs of Glx/tCr and tCho/tCr did not show a significant difference between the groups. Lateralization of the interictal epileptiform activity corresponded with the lower tNAA/tCr ratio in 10 of 13 patients. MRI revealed a hippocampal asymmetry in four of 13 in the RE group, three of them showed concordance between the lateralization of the lower tNAA/tCr ratio and the smaller hippocampus. In the control group, a subtle asymmetry in four of 13 children was found.

Conclusions: A significant asymmetry of the hippocampal regions, measured by tNAA/tCr ratios, indicates an abnormal neuronal function in children with RE.
The Predictive Value of Electroencephalogram during Early Infancy for Later Development of West Syndrome in Infants with Cystic Periventricular Leukomalacia
Authors: Suzuki Motomasa , Okumura Akihisa , Watanabe Kazuyoshi , Negoro Tamiko , Hayakawa Fumio , Kato Toru , Itomi Kazuya , Kubota Tetsuo , Maruyama Koichi
Published: March 2003

Summary: Purpose:The aim of this study was to elucidate a predictive value of electroencephalogram (EEG) during early infancy for later development of West syndrome (WS) in premature infants with cystic periventricular leukomalacia (PVL).

Methods:The subjects of this study were 19 infants with cystic PVL born between 1992 and 1996. EEGs were recorded at 3 months of corrected age (CA) in all of them. We divided these 19 infants into the following two groups; group A (n = 9), no paroxysmal discharge was recognized; and group B (n = 10), paroxysmal discharges were recognized.

Results:In none of the infants in group A did WS develop. Subsequent EEGs were normal in all infants in group A. WS developed in seven of 10 infants in group B. The occurrence of WS is significantly higher in group B than in group A. The mean age at the onset of WS was 6 months of CA. Paroxysmal discharges in infants in group B were observed as irregular spikes‐and‐waves and polyspikes‐and‐waves, mainly in bilateral parietooccipital areas. In seven of eight patients with severe MRI findings in group B, WS developed.

Conclusions:Paroxysmal discharges during early infancy were correlated with later development of WS in infants with cystic PVL. The possibility of developing WS had increased in the children with the combination with EEG and MRI findings.
Electrocardiographic Changes at the Onset of Epileptic Seizures
Authors: Leutmezer Fritz , Schernthaner Christiana , Lurger Stefanie , Pötzelberger Klaus , Baumgartner Christoph
Published: March 2003

Summary: Purpose:We studied heart‐rate (HR) changes at the transition from the preictal to the ictal state in patients with focal epilepsies to gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function.

Methods:We assessed ECG changes during 145 seizures recorded with scalp EEG in 58 patients who underwent video‐EEG monitoring. Consecutive RR intervals were analyzed with a newly developed mathematical method for a total of 90 s.

Results:Ictal‐onset tachycardia occurred in 86.9% of all seizures, whereas bradycardia was documented only in 1.4%. The incidence as well as the amount of ictal HR increase was significantly more pronounced in patients with mesial temporal lobe epilepsy (TLE) as compared with those with non‐lesional TLE or extratemporal epilepsy. Moreover, right hemispheric seizures were associated with ictal‐onset tachycardia. On average, ictal HR increase preceded EEG seizure onset by 13.7 s in TLE patients and 8.2 s in patients with extratemporal epilepsy. This difference was significant. Ictal HR changes could be classified according to their temporal evolution into two different patterns. These two patterns differed significantly between the temporal lobe and the extratemporal epilepsy patient group.

Conclusions:Epileptic discharges directly influence areas of the central autonomic network, thus regulating HR and rhythm. Such changes occur before ictal discharges appear on surface electrodes. Our newly developed method may be of potential use for clinical applications such as automatic seizure‐detection systems. Moreover, our method might help to clarify further the basic mechanisms of interactions between heart and brain.
Epileptogenesis During Development: Injury, Circuit Recruitment, and Plasticity
Authors: Sankar Raman , Shin Don , Liu Hantao , Wasterlain Claude , Mazarati Andrey
Published: March 2003

Summary:  Purpose: To use animal models of variable seizure induction in rats at different developmental stages to determine contributing factors for spontaneous seizures resulting from status epilepticus (SE) early in life.

Methods: Two models of SE with distinct modes of seizure induction, lithium–pilocarpine (LiPC) and perforant path stimulation (PPS), were used at different ages. Multiple methods of determining neurodegeneration during an acute period and plastic changes in those monitored during the chronic phase were used.

Results: Different modes of seizure induction lead to varying types and extents of damage, dependent on the age of the animals at the time of insult. LiPC resulted in injury to animals as young as 2 weeks and became widespread in animals 3 weeks old, whereas widespread damage after PPS was not seen until P35. Rats at an age with widespread damage in response to seizures also showed extensive immediate‐early gene activation and often developed spontaneous seizures and features of hippocampal plasticity seen in the epileptic brain.

Conclusions: SE early in life results in multiple consequences to the developing brain. These changes, coexisting in the nonepileptic brain, can overlap in a maladaptive combination to result in the diseased state of epilepsy. The consequence of early seizures in immature animals is a function of both the developmental stage and the method of seizure induction.
Damage, Reorganization, and Abnormal Neocortical Hyperexcitability in the Pilocarpine Model of Temporal Lobe Epilepsy
Authors: Sanabria Emilio R. Garrido , Da Silva Alexandre V. , Spreafico Roberto , Cavalheiro Esper A.
Published: March 2003

Summary:  Purpose: Clinical, neuropathological, and electrophysiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). In most cases, limbic‐originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. The present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine‐treated epileptic rats.

Methods: Adult epileptic animals showing six to seven seizures/week and saline‐injected rats were selected for neurohistology. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and stained with cresyl violet (Nissl). Immunocytochemistry (ICC) was performed using anti‐neurofilament (SMI‐311) antibody. Extracellular (layer II/III) and intracellular (layer V) recordings were performed in coronal sensorimotor neocortical slices. Several electrophysiological aspects were examined such as evoked responses, intrinsic properties, and firing patterns of layer V pyramidal cells.

Results: Nissl staining showed a significant decrease of cortical thickness in epileptic rats when compared with controls, particularly in superficial layers (II–IV). Such abnormalities were also revealed by SMI‐311 staining. SMI‐311–labeled dendrite arborizations were more complex in layers I–II of epileptic rats. Epileptic rats manifested several abnormalities in extracellular field responses including hyperresponsiveness and presence of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐mediated polysynaptic activity. Although no significant changes were observed concerning passive intrinsic properties, it was possible to detect a higher proportion of bursting neurons distributed in layer V (60%) of epileptic rats compared with 22% in control slices.

Conclusions: Taken together, our findings indicate damage, reorganization, and chronic hyperexcitability of sensorimotor neocortex in experimental TLE.