bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Topiramate in the Prevention of Childhood Headaches
Authors: Hershey Andrew D. , Powers Scott W. , Vockell Anna‐Liisa B. , LeCates Susan , Kabbouche Marielle 
Published: March 2003

Background.—Migraine is a significant problem for many children. Topiramate has been suggested to be effective for the prophylaxis of migraine in adults, but has not yet been examined in children. The drug has been demonstrated to be safe and effective for childhood seizure disorders. The objective of this study was to demonstrate the safety and efficacy of topiramate for the prevention of pediatric migraine.Methods.—Children with frequent migraine were prescribed topiramate for headache prevention. Dosages, serum levels, and Serum Glutamic Oxalacetic Transaminase (SGOT) levels were monitored. Changes in frequency, severity, and duration of headaches were recorded and changes in headache‐related disability using PedMIDAS also were measured.Results.—Ninety‐seven children were treated with topiramate, and 75 were reevaluated 88.7 ± 35.7 days later, 41 were seen at a second follow‐up, and 17 were seen at a third follow‐up evaluation. The daily dose reached at second evaluation was 84.0 ± 38.6 mg/day or 1.42 ± 0.74 mg/kg/day. This corresponded to a mean serum level of 2.8 ± 1.6 μg/mL. The mean headache frequency was reduced from 16.5 ± 10.0 to 11.6 ± 10.2 days per month (P<0.001) with a further reduction to 9.4 ± 8.4 days by the second follow‐up (P<0.001). Severity and duration of headache also were reduced. Headache disability improved, with a reduction of Pediatric Migraine Disability Assessment score from 36.0 ± 42.3 to 20.8 ± 34.0 at the first follow‐up (P<0.05), 19.1 ± 22.0 at the second follow‐up (P<0.005), and 10.9 ± 16.9 at the third follow‐up (P<0.001). Most patients tolerated topiramate well. The most common side effects reported were cognitive (12.5%), weight loss (5.6%), and sensory (2.8%).Conclusions.—Topiramate is potentially an effective prophylactic medication for children with frequent migraine.
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.
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.