bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Use of Sumatriptan: A Patient Interview Study
Authors: Rahimtoola H. , Buurma H. , Tijssen C.C. , Leufkens H.G. , Egberts A.C.G.
Published: March 2003

Objective.—To investigate the possible reasons associated with the use of a single prescription of sumatriptan.

Background.—A few population‐based studies concerning the usage patterns of sumatriptan have revealed a relatively high incidence (approximately 40%) of sumatriptan users who utilize only a single prescription of the drug.

Design and Methods.—Using automated prescription data from 11 community pharmacies, we identified single and multiple sumatriptan prescription recipients. The data were collected from May 1, 1998, to April 30, 2000. Several patient‐ and medication‐related variables possibly associated with single recipiency of sumatriptan were analyzed. In addition, single recipients of sumatriptan were invited for an interview and asked a number of questions related to their clinical status and their experience with the medication.

Results.—Four hundred ninety‐five, first‐time users of sumatriptan were identified during the patient selection period, of whom 38% were single recipients of sumatriptan. Of the latter, 102 patients were considered eligible for interview. Reasons for terminating treatment after only 1 prescription included: inefficacy and/or occurrence of side effects, 78% (n = 79); uncertain diagnosis of migraine, 39.2% (n = 40); and reduction in headache frequency, 33.3% (n = 34). Almost half of the population had terminated treatment without having consulted their physician. More than half relied upon the use of over‐the‐counter (OTC) analgesics after having tried sumatriptan. Compared to multiple users of sumatriptan, single recipients were far less likely to have used another form of migraine treatment prior to (odds ratio, 0.35; [95% confidence interval, 019 to 0.67]) and after (odds ratio, 0.34 [95% confidence interval, 0.19 to 0.63]) initiating sumatriptan. Furthermore, single recipients had demonstrated an increased tendency towards benzodiazepine use prior to receiving sumatriptan (odds ratio, 1.80 [95% confidence interval, 1.00 to 3.28]).

Conclusions.—Single use of a sumatriptan prescription reveals some issues that may impact negatively the provision of effective migraine management. These include: rapidly developing dissatisfaction with the treatment provided and a lower tendency to seek out medical care. Our results also suggest that the drug may be used (inappropriately) as a diagnostic tool.
Fixation‐off Sensitivity in an Adult with Symptomatic Occipital Epilepsy
Authors: Kurth Christoph , Bittermann Hans‐Joachim , Wegerer Viola , Bleich Stefan , Steinhoff Bernhard J.
Published: March 2003

Summary: An adult patient had EEG occipital spike fixation‐off sensitivity and spontaneous occipital seizures due to perinatal asphyxia with bioccipital hemorrhage. EEG abnormalities consisted of repetitive posterior spikes that occurred when the eyes were closed and other conditions of fixation‐off. Magnetic resonance imaging (MRI) documented severe posterior lesions with wallerian degeneration of the optic radiation. Electron capture detector single‐photon emission computed tomography (ECD‐SPECT) during the state of fixation‐off showed regional hyperperfusion in the right posterior regions. We suggest that partial denervation of the primary visual cortex in this patient resulted in an increased cortical excitability and that the inhibitory effect of central vision and fixation leads to a suppression of spontaneous epileptic activity. This unusual symptomatic case may serve as a model for the pathophysiology in the more often reported cases of idiopathic benign epilepsy syndrome of childhood.
Ictal and Nonictal Paroxysmal Events in Infantile Neuroaxonal Dystrophy: Polygraphic Study of a Case
Authors: Santucci Margherita , Ambrosetto Giovanni , Scaduto M. Cristina , Morbin Michela , Tzolas E. Vittoria , Rossi Paola Giovanardi
Published: March 2003

Summary:A 7.5‐year‐old girl, with infantile neuroaxonal dystrophy (INAD), showed a gradual deterioration from 16 months; at age 5 years she was bedridden, with severe tetraplegia, strabismus, nystagmus and optic atrophy, and dementia. From age 5.5 years, she had paroxysmal tonic events. Videopolygraphic recordings disclosed two different kinds of motor events: (a) epileptic tonic seizures, in wakefulness and sleep, associated with autonomic changes and ictal EEG discharges; and (b) nonepileptic prolonged clusters of brief tonic spasms, without ictal modifications of the EEG. Both motor events were characterized by a minimal and clinically similar tonic contraction of the upper extremities. Video‐polygraphic studies are mandatory for a correct paroxysmal event classification and treatment in INAD patients.
GABAergic Mechanisms in Epilepsy
Authors: Treiman David M.
Published: March 2003

Summary: γ‐Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tone that counterbalances neuronal excitation. When this balance is perturbed, seizures may ensue. GABA is formed within GABAergic axon terminals and released into the synapse, where it acts at one of two types of receptor: GABAA, which controls chloride entry into the cell, and GABAB, which increases potassium conductance, decreases calcium entry, and inhibits the presynaptic release of other transmitters. GABAA‐receptor binding influences the early portion of the GABA‐mediated inhibitory postsynaptic potential, whereas GABAB binding influences the late portion. GABA is rapidly removed by uptake into both glia and presynaptic nerve terminals and then catabolized by GABA transaminase. Experimental and clinical study evidence indicates that GABA has an important role in the mechanism and treatment of epilepsy: (a) Abnormalities of GABAergic function have been observed in genetic and acquired animal models of epilepsy; (b) Reductions of GABA‐mediated inhibition, activity of glutamate decarboxylase, binding to GABAA and benzodiazepine sites, GABA in cerebrospinal fluid and brain tissue, and GABA detected during microdialysis studies have been reported in studies of human epileptic brain tissue; (c) GABA agonists suppress seizures, and GABA antagonists produce seizures; (d) Drugs that inhibit GABA synthesis cause seizures; and (e) Benzodiazepines and barbiturates work by enhancing GABA‐mediated inhibition. Finally, drugs that increase synaptic GABA are potent anticonvulsants. Two recently developed antiepileptic drugs (AEDs), vigabatrin (VGB) and tiagabine (TGB), are examples of such agents. However, their mechanisms of action are quite different (VGB is an irreversible suicide inhibitor of GABA transaminase, whereas TGB blocks GABA reuptake into neurons and glia), which may account for observed differences in drug side‐effect profile.
Idiopathic Epilepsy and Paroxysmal Dyskinesia
Authors: Guerrini Renzo
Published: March 2003

Summary:Although some motor manifestations of epilepsy and of paroxysmal dyskinesia may be difficult to differentiate clinically, the current understanding is that the two disorders are clinically distinct. However, there are several recent reports of families in which different individuals had either disorder or both manifestations, with age‐related expression. Co‐occurrence makes it likely that a common, genetically determined, pathophysiologic abnormality is variably expressed in the cerebral cortex and in basal ganglia. A rather homogeneous syndrome of autosomal dominant infantile convulsions and paroxysmal (dystonic) choreoathetosis (ICCA) was described in six families from France, China and Japan. Linkage analysis in the French and Chinese families allowed the mapping of the disease gene in a 10‐cM interval within the pericentromeric region of chromosome 16. An Italian pedigree in which three members in the same generation were affected by rolandic epilepsy, paroxysmal exercise‐induced dystonia (PED), and writer's cramp was subsequently reported. Linkage analysis showed a common homozygous haplotype in a critical region spanning 6 cM and entirely included within the ICCA critical region. Clinical analogies and linkage findings suggest that the same gene could be responsible for rolandic epilepsy, PED, writer's cramp (WC), and ICCA, with specific mutations accounting for each of these mendelian disorders. Evidence for a major gene or a cluster of genes for epilepsy and paroxysmal dyskinesia to the pericentromeric region of chromosome 16 is reinforced by the recent linkage of a family with autosomal dominant paroxysmal dyskinesia to a critical region partially overlapping with ICCA and contiguous to the RE‐PED‐WC regions. Additional autosomal dominant pedigrees are on record, from Australia and Italy, in which epilepsy was variably associated with paroxysmal kinesigenic or exercise‐induced dystonia. Ion channel genes are potentially interesting candidates for syndromes featuring both these paroxysmal neurologic disorders. Increased awareness of their possible co‐occurrence will certainly increase the number of observations in the next few years.
Epilepsy in the Elderly: The Use of Tiagabine
Authors: Pedersen Birthe
Published: March 2003

Summary: The incidence of epilepsy increases sharply in patients older than 60 years. There is a clear need for clinical trials designed specifically for this age group, as elderly patients differ from younger patients with epilepsy with respect to seizure etiology, coexisting diseases, concomitant drug therapy, and drug disposition. The new antiepileptic drugs (AEDs) are often associated with fewer side effects than are the traditional AEDs and may be particularly useful in the elderly. The pharmacokinetics of tiagabine (TGB) are not significantly modified in elderly patients, although elimination is more rapid in the presence of enzyme‐inducing AEDs. Efficacy and tolerability data on TGB in elderly patients is currently limited, and a formal trial of TGB monotherapy in this age group is needed.
MOSES: An Educational Program for Patients with Epilepsy and Their Relatives
Authors: Ried S. , Specht U. , Thorbecke R. , Goecke K. , Wohlfarth R.
Published: March 2003

Summary: The knowledge of patients with epilepsy about their own condition is poor, and thus the need for educational programs for people with epilepsy has long been recognized. However, no such programs have been established in their routine care. The Modular Service Package Epilepsy (MOSES) now tries to fill this gap for patients in German‐speaking countries. The program was developed by a multidisciplinary group (neurologists, nonmedical professional helpers, and representatives of national epilepsy associations) for people with epilepsy older than 16 years, independent of the kind and severity of their epilepsy. MOSES is designed for group education and can be used in inpatient and outpatient settings in epilepsy centers, in clinics, and by neurologists in private practice. The program aims to help patients achieve a better understanding of their disease, to gain more self‐confidence, and to take over responsibility, thus supporting patients to become experts in managing their own illness. Being modular in structure, MOSES includes nine units: living with epilepsy, epidemiology, basic knowledge, diagnostics, therapy, self‐control, prognosis, psychosocial aspects, and network epilepsy. MOSES consists of a workout manual for patients and a trainer manual. For potential trainers, special “train‐the‐trainer seminars” are offered and considered mandatory. About 400 patients have participated in a MOSES training program in Germany, Switzerland, and Austria. The efficacy of the program is currently been evaluated.
Mechanism of the Inhibitory Effect of Histamine on Amygdaloid‐Kindled Seizures in Rats
Authors: Okuma Chihiro , Hirai Tadashi , Kamei Chiaki
Published: March 2003

Summary:  Purpose: The mechanism of the inhibitory effect of histamine on amygdaloid‐kindled seizures was investigated in rats.

Methods: Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. A guide cannula made of stainless steel tubing was implanted into the right lateral ventricle. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. EEG was recorded with an electroencephalograph; stimulation of the amygdala was applied bipolarly every day by a constant‐current stimulator and continued until a generalized convulsion was obtained.

Results: Intracerebroventricular (i.c.v.) injection of histamine at doses of 2–10 μg resulted in a dose‐related inhibition of amygdaloid‐kindled seizures. I.c.v. injection of calcium chloride at doses of 10–50 μg and A23187 at doses of 2–10 μg also caused dose‐dependent inhibition of amygdaloid‐kindled seizures. Calcium chloride at a dose of 10 μg, which showed no significant effect on amygdaloid‐kindled seizures when used alone, significantly potentiated the effect of histamine. Similar findings were observed with A23187 at a dose of 2 μg. In addition, EGTA and EGTA/AM antagonized the inhibition of kindled seizures induced by histamine. Moreover, the inhibition of kindled seizures induced by histamine was antagonized by KN62. However, calphostin C did not antagonize the inhibitory effect of histamine.

Conclusions: These results indicated that histamine‐induced inhibition of amygdaloid‐kindled seizures may be closely associated with a calcium calmodulin‐dependent protein kinase II activation pathway.
Premature Ovarian Failure in Women with Epilepsy
Authors: Klein Pavel , Serje Adriana , Pezzullo John C.
Published: March 2003

Summary:  Purpose: Women with epilepsy (WWE) have an increased risk for several reproductive endocrine disorders that may affect their fertility. The incidence of premature ovarian failure (POF) in women with epilepsy has not been systematically studied. This study examined the incidence of POF in women with epilepsy.

Methods: Fifty consecutively evaluated cognitively normal women with epilepsy, aged 38–64 years, whose seizures began before age 41 years, were interviewed for symptoms of perimenopause and menopause. Endocrine studies, performed in women aged 45 years or younger at the time of evaluation, included serum follicle‐stimulating hormone (FSH; done on menstrual cycle day 3 in menstruating women), inhibin A levels when FSH was normal, thyroid‐stimulating hormone (TSH), prolactin, and, in menstruating women, menstrual cycle day 20 serum progesterone level. Nonsurgical premature menopause was defined as secondary amenorrhea of >12 months' duration with FSH levels of >14 International Units (IU) in women younger than 42 years. Premature perimenopause was defined by the presence of one or more of the following: somatic perimenopausal symptoms; change in previously regular menstrual cycles without evidence of other reproductive endocrine disturbance; and FSH level of >14 IU or inhibin A level of <7 pg/ml. Similarly aged neurologically normal women seen in the menopause and sleep clinics served as control subjects. Statistical analysis included Fisher's exact test, Kruskal–Wallis test, t test, and multivariate logistic regression analysis with significance set at p < 0.05.

Results: Seven (14%) of 50 women with epilepsy had nonsurgical premature perimenopause (six of seven) or menopause (one of seven), compared with three of 82 control (p = 0.042). Five of 41 women with localization‐related epilepsy (LRE) had POF compared with two of nine women with primary generalized epilepsy (PGE; p = 0.595). Mean age of POF was 39.6 years (range, 37–42 years). Seizure duration, age at seizure onset, seizure severity and lateralization, smoking history, age of menarche, body mass index and incidence of depression was not statistically different between women with and without POF. There was no statistically significant association between POF and antiepileptic drugs (AEDs). Women with POF were more likely to have had catamenial exacerbation of their seizures than were women without POF (p = 0.02).

Conclusions: Women with epilepsy have an increased risk for developing POF. This finding should be considered in counseling women with epilepsy on family planning.
AWD 140‐190: A Potent Anticonvulsant in the Amygdala‐Kindling Model of Partial Epilepsy
Authors: Tober Christine , Löscher Wolfgang , Hönack Dagmar , Bartsch Reni
Published: March 2003

Summary:  Purpose: Evaluation of the effect of the new anticonvulsant drug, AWD 140‐190 [4‐(p‐bromophenyl)‐3‐morpholino‐1H‐pyrrole‐2‐carboxylic acid methyl ester] on focally induced seizures and on epileptogenesis in the kindling model.

Methods: Effects of AWD 140‐190 were studied in amygdala kindled rats after oral and intraperitoneal administration. In addition, the effect on kindling development was evaluated. In all experiments, behavioral changes in the rats in response to AWD 140‐190 were monitored closely.

Results: AWD 140‐190 exerted potent anticonvulsant activity against focal seizures. After intraperitoneal and oral administration in fully kindled rats, the substance dose‐dependently increased the threshold for induction of afterdischarges starting at 15 mg/kg. AWD 140‐190 only weakly influenced the seizure severity of the animals after stimulation at the elevated afterdischarge threshold current. No adverse effects were observed up to 30 mg/kg after intraperitoneal and oral administration in the open field and in the rotarod test. No differences were found between kindled and nonkindled rats when comparing neurotoxicity of AWD 140‐190. Prolonged treatment with AWD 140‐190 during kindling acquisition did not prevent kindling, but significantly retarded the development of fully kindled seizures during the treatment.

Conclusions: This study demonstrates that AWD 140‐190 has anticonvulsant effects in the amygdala kindling model in rats, suggesting that the substance is particularly effective against partial seizures. AWD 140‐190 is orally active and devoid of neurotoxic effects in anticonvulsant doses, thus indicating that this compound has potential for antiepileptic therapy. AWD 140‐190 retards the kindling development during the treatment. This effect could be explained by the acute anticonvulsant effect of the substance.
Anticonvulsant Efficacy of Gabapentin on Kindling in the Immature Brain
Authors: Lado F. A. , Sperber E. F. , Moshé S. L.
Published: March 2003

Summary: The anticonvulsant and motor effects of gabapentin (GBP) were evaluated in rat pups aged 16–17 days. Fourteen‐day‐old rat pups received an implanted stimulating electrode in the amygdala unilaterally. Kindled seizures were produced on day 16 of life by repeatedly applying an electrical current stimulus to the amygdala electrode. Animals received kindling stimulation until they achieved three consecutive generalized convulsions. On day 17, rat pups received one of four doses of GBP 10, 25, 50, or 100 mg/kg. After receiving GBP, rat pups again received electrical stimulation to the amygdala electrode to determine the extent to which GBP prevented the kindled seizure. Anticonvulsant effects were found at doses as low as 10 mg/kg. A separate group of naïve rats received GBP to determine the motor effects of each treatment dose. Impaired motor performance, quantified as time on a balance beam, occurred at doses of ≥50 mg/kg. In summary, our data indicate that in immature rats, GBP exerts an anticonvulsant effect against kindled seizures at doses that do not significantly impair motor performance.
Comparative Cognitive Effects of Carbamazepine and Gabapentin in Healthy Senior Adults
Authors: Martin Roy , Meador Kimford , Turrentine Luanne , Faught Edward , Sinclair Kristina , Kuzniecky Ruben , Gilliam Frank
Published: March 2003

Summary:  Purpose: This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double‐blind crossover design.

Methods: Thirty‐four senior adults were randomized to receive one of the two drugs followed by a 5‐week treatment period. A 4‐week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase.

Results: Fifteen senior adults (mean age, 66.5 years; range, 59–76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 μg/ml; GBP, 7.1 μg/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS).

Conclusions: Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The magnitude of difference between the two AEDs across the cognitive variables was modest. Self‐reported mood was not significantly affected by either AED. However, overall tolerability and side‐effect profile of CBZ were poorer than those of GBP in senior adults at doses and titration rates reported in this study.
Visual Function is Stable in Patients Who Continue Long‐Term Vigabatrin Therapy: Implications for Clinical Decision Making
Authors: Paul Scott R. , Krauss Gregory L. , Miller Neil R. , Medura Marianne T. , Miller Tracy A. , Johnson Mary A.
Published: March 2003

Summary:  Purpose: Vigabatrin (VGB) has been shown to cause visual field constriction and other forms of mild visual dysfunction. We determined the safety of continuing VGB therapy in patients who had received prolonged treatment (>2 years) with the drug by serially monitoring changes in visual function over a 1‐year period of continued therapy. We also followed up patients who discontinued VGB to see whether alternative therapies are effective.

Methods: Fifteen of 17 patients who continued VGB therapy had visual‐function testing (visual acuity, color vision, kinetic and static perimetry) every 3 months for 1 year. Eighteen patients who discontinued VGB were given alternative antiepileptic drugs (AEDs); their seizure responses were measured after ≥3 months of treatment.

Results: Patients continuing VGB showed no worsening of visual acuity, color vision, or visual‐field constriction beyond that measured in the initial test. Many patients who discontinued VGB had good seizure control with either newer or previously unsuccessful AEDs.

Conclusions: For patients who have an excellent response to VGB and only mild visual changes, continued therapy may be safe with close visual monitoring. Patients who do not have a significant reduction in seizures or who experience considerable visual dysfunction with VGB may respond well to alternative therapies.
AIDA, a Class I Metabotropic Glutamate‐receptor Antagonist Limits Kainate‐induced Hippocampal Dysfunction
Authors: Renaud Johanne , Emond Martine , Meilleur Sébastien , Psarropoulou Caterina , Carmant Lionel
Published: March 2003

Summary:  Purpose: In the developing animal, intraperitoneal injections of kainic acid (KA) lead to a prolonged initial seizure followed by chronic recurrent seizures and long‐term hippocampal dysfunction. We investigated whether the class I metabotropic glutamate receptor (mGluR) antagonist 1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) is neuroprotective in the KA model of epilepsy.

Methods: Immature rats aged postnatal day 20 (P20) and P30 were injected with fixed volumes of KA, KA + AIDA, AIDA, or saline. We monitored recurrent seizures. Thirty days later, we tested hippocampal function with the Morris water‐maze test or prepared hippocampal slices to record extracellularly evoked and spontaneous potentials from the CA1 area. In a third group, we performed neuronal counts.

Results: In both age groups, acute seizures were similar in KA and KA + AIDA groups. Rare spontaneous recurrent seizures occurred only in KA‐injected rats. The KA P20 group performed significantly worse than controls in the water‐maze test. The KA + AIDA group showed impaired performance on day 1, but learning improved substantially, reaching control values in the remaining 3 days. The P30 KA rats performed worse than controls on all trial days, whereas the KA + AIDA rats improved by day 3, but did not reach control values. Electrophysiologic recordings showed small but consistent differences between KA and control animals, suggestive of an adaptive modification in the γ‐aminobutyric acid (GABA)ergic system, reversed by AIDA. On histology, we observed a loss of CA1 interneurons in both ages. Cell loss was reversed by the use of AIDA.

Conclusions: Blockade of the class I mGluR during KA‐induced seizures in the developing brain limits seizure‐induced hippocampal dysfunction.
Epileptic Negative Myoclonus in a Newborn with Hemimegalencephaly
Authors: Guzzetta Francesco , Battaglia Domenica , Lettori Donatella , Deodato Federica , Sani Emanuela , Randò Teresa , Ricci Daniela , Acquafondata Celeste , Faienza Carmine
Published: March 2003

Summary:  Purpose: We report the case of a male newborn with Ohtahara syndrome and right hemimegalencephaly who presented epileptic negative myoclonus in the first days of life.

Methods: Prolonged polygraphic studies were performed, as well as MRI and a full clinical examination.

Results: EEG showed a constant and nonreactive pattern of burst suppression. There were several kinds of electro‐clinical seizures (generalized myoclonia, short atonias, typical spasm and tonic spasms) at the beginning of the EEG's burst. The periods of EMG silence, lasting less than 300 ms, were associated with stereotyped EEG transients.

Conclusions: Epileptic negative myoclonus can be observed also in neonatal age. The short transient impairment of motor function observed in the newborn seems linked to the slow component of spike‐wave discharge, but its mechanism is still not clear.
Interictal Epileptiform Discharges Relate to 1H‐MRS–detected Metabolic Abnormalities in Mesial Temporal Lobe Epilepsy
Authors: Park Sun Ah , Kim Gyu Sik , Lee Seung Koo , Lim Sung Ryoung , Heo Kyoung , Park Soo Chul , Chang Jin Woo , Kim Dong Ik , Lee Byung In
Published: March 2003

Summary:  Purpose: To examine whether the distribution of interictal epileptiform discharges (IEDs) recorded from foramen ovale electrodes (FOEs) correlates with metabolite levels in medial structures of the temporal lobes in patients with mesial temporal lobe epilepsy (MTLE).

Methods: We studied 34 patients with MTLE. The lateralization ratio of IEDs was calculated after counting IEDs recorded from FOEs during prolonged video‐EEG monitoring. Metabolite ratio between N‐acetylaspartate (NAA) and creatine (Cr) was calculated in each medial temporal structure. The correlation between the lateralization ratio of IEDs and metabolic ratio was evaluated.

Results: The asymmetry indexes of IEDs correlated with the asymmetry index of NAA/Cr ratio in the medial temporal structure (ρ = –0.380; p = 0.027). Analysis of IEDs and metabolite ratio revealed a significant inverse relation in the contralateral side to the major epileptogenic focus (ρ = –0.360; p = 0.037); however, this significance was not present in the ipsilateral side (ρ = –0.018; p = 0.921).

Conclusions: There is a correlation between the neuronal dysfunction or damage detected by MRS and the epileptic activity in the contralateral medial temporal structure. Our results suggest that the pathomechanism underlying the contralateral reduction of NAA/Cr ratio, frequently observed in patients with MTLE, might be related to the process of epileptogenesis generating the independent contralateral IEDs.
Different Neurophysiologic Patterns of Myoclonus Characterize Lennox–Gastaut Syndrome and Myoclonic Astatic Epilepsy
Authors: Bonanni Paolo , Parmeggiani Lucio , Guerrini Renzo
Published: March 2003

Summary:  Purpose: To study the neurophysiologic characteristics of epileptic myoclonus in patients with Lennox–Gastaut syndrome (LGS) and myoclonic astatic epilepsy (MAE).

Methods: Three patients with symptomatic LGS (mean age, 15 years ± 4) and three with cryptogenic MAE (mean age, 9 years ± 3) were studied. Temporal relationships between electroencephalographic (EEG) and electromyographic activity were studied by analyzing latencies of EEG activity related to the onset of single myoclonic jerks, by using burst‐locked EEG averaging where necessary.

Results: LGS: neurophysiologic analysis indicated that jerks and the accompanying premyoclonic spikes showed latency differences between sides (mean ± SD, 18 ± 5 ms for both) with a constant leading side in each patient. The premyoclonic spike latency was 20 ± 10 ms (mean ± SD). Topographic voltage mapping of the premyoclonic spike peak showed a unilateral frontal distribution. MAE: muscles from both sides were activated synchronously, and the EEG correlate was a generalized spike–wave, in which the negative peak of the spike preceded the generalized jerks by 30 ± 2 ms (mean ± SD). Topographic voltage mapping of the premyoclonic spike peak showed a diffuse distribution of the electrical field, predominating over the anterior regions, but not lateralized.

Conclusions: These neurophysiologic findings indicate that epileptic myoclonus in LGS originates from a stable generator in the frontal cortex, to spread to contralateral and ipsilateral cortical areas, whereas myoclonus in MAE appears to be a primary generalized epileptic phenomenon.
Preeminence of Extrahippocampal Structures in the Generation of Mesial Temporal Seizures: Evidence from Human Depth Electrode Recordings
Authors: Wennberg Richard , Arruda Francisco , Quesney Luis Felipe , Olivier André
Published: March 2003

Summary:  Purpose: To examine the intralimbic localization and morphology of mesial temporal seizure onsets and to correlate the findings with patterns of initial seizure spread and the presence or absence of clinical manifestations.

Methods: Eighteen patients with temporal lobe epilepsy were investigated with intracranial depth electrodes implanted in the amygdala (AM), anterior hippocampus (HP), and parahippocampal gyrus (PH). Focal and regional ictal‐onset morphologies were classified as rhythmic limbic spiking <2 Hz (RLS), spike‐and‐wave activity >2 Hz (S/W), rhythmic polyspike activity >13 Hz (RPS), and rhythmic sharp activity <13 Hz (RS).

Results: Onset morphologies in 389 total seizures (260 regional + 129 focal) were 50% RPS, 35% RS, 11% RLS, and 4% S/W. Focal AM or HP onsets (30% and 58% of focal onsets, respectively) were more likely to show RLS, whereas RPS was more common in regional onsets. Most patients showed two or more different morphologies and focal onsets at more than one ipsilateral limbic site. Seizure propagation and clinical manifestations were significantly more common with AM or PH onsets (both 67% clinical seizures): only 23% of focal HP onsets resulted in clinical seizures.

Conclusions: (a) There is substantial inter‐ and intrapatient variability in the morphology and localization of mesial temporal seizure onsets, which suggests that the epileptogenic temporolimbic system may be conceptualized as a dynamic network containing a multiplicity of potential ictal generators; (b) Seizures beginning in the AM or PH are more likely to propagate and give rise to clinical manifestations than are focal‐onset HP seizures, which suggests that inhibitory circuits within the HP may function to prevent seizure spread.
Preliminary Results on Pregnancy Outcomes in Women Using Lamotrigine
Authors: Tennis Patricia , Eldridge R. R. ,   International Lamotrigine Pregnancy Registry Scientific Advisory Committee
Published: March 2003

Summary:  Purpose: In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pregnancies exposed to LTG polytherapy during the first trimester.

Methods: LTG pregnancy exposures are voluntarily reported to the registry by health care providers before they are aware of each pregnancy outcome. Pregnancy‐outcome ascertainment is obtained through subsequent follow‐up with the reporting health care provider, and each reported birth defect is reviewed by an expert pediatrician. The percentage with major birth defects in pregnancies with known birth defect status was calculated for LTG monotherapy and for polytherapy stratified by trimester of exposure.

Results: The registry identified 334 first‐trimester LTG pregnancy outcomes exposed to LTG monotherapy or polytherapy during the first trimester and involving either a live birth with or without a major birth defect or an abortion with a major birth defect. After exposure to LTG monotherapy, the percentage with major birth defects exposed to LTG monotherapy was three (1.8%) of 168 [95% confidence interval (CI), 0.5–5.5%]. There were five (10%) major birth defects observed in 50 outcomes after LTG polytherapy involving valproic acid (VPA; 95% CI, 3.7–22.6%) during the first trimester. The observed proportion of major defects after LTG polytherapy without VPA during the first trimester was five (4.3%) of 116 (95% CI, 1.6–10.3%). No specific patterns of major birth defects in any subgroup or within the registry as a whole were observed.

Conclusions: The sample sizes for individual regimens are too small to rule out small increases in frequency of all major birth defects or even large increases in frequency of rare major birth defects. However, the percentage of outcomes with major birth defects after LTG monotherapy in this study and in another similar pregnancy registry in the United Kingdom did not differ from that reported in the recent literature for women with epilepsy receiving antiepileptic drug monotherapy (4%). The frequency of major malformations after exposures of LTG–VPA is higher than that after the LTG monotherapy or LTG polytherapy regimens without VPA. Although there are published data on frequency of major malformations after VPA exposures in pregnancy, between‐study differences in methods and source populations and the wide confidence intervals around the estimate for LTG and VPA limit the utility of comparison with such data, and no conclusions are made at this time about this combination. The continued registration of exposed pregnancies to an exposure registry as early as possible in the pregnancy before any knowledge of the outcome, and before any prenatal testing, will enhance the power of such data.
Behavioral Problems in Children with Newly Diagnosed Idiopathic or Cryptogenic Epilepsy Attending Normal Schools Are in Majority Not Persistent
Authors: Oostrom Kim J. , Schouten Anneke , Kruitwagen Cas L. J. J. , Peters A. C. B. , Jennekens‐Schinkel Aagje ,   Dutch Study Group of Epilepsy in Childhood (DuSECh)
Published: March 2003

Summary:  Purpose:To investigate relevant adults' perceptions of behavioral problems in 66 children with newly diagnosed “epilepsy only” and in 63 healthy gender‐matched classmates.

Methods:Parents' and teachers' perceptions of the children's behavioral problems were quantified by using the Total Problem score of the Child Behavior Checklist (CBCL) and the Teacher's Report Form (TRF), after correction for epilepsy‐related item ambiguity. Questionnaires were filled out immediately after diagnosis and 3 and 12 months later. Relations with demographic and educational variables, school attitudes, and interview‐derived prior adversities were analyzed.

Results:As a group, children with cryptogenic rather than those with idiopathic epilepsy have more behavioral problems than do healthy classmates. Family troubles and long‐standing behavioral and learning problems are associated with more behavioral problems. The child's adaptation to the adversity of epilepsy onset is important. No adverse effect of antiepileptic drug (AED) treatment was found. Although the percentages of patients with clinically relevant (mean of controls + 2 SD) behavioral problems are consistently 25% (parents) and 22% (teachers), at each assessment, different children contribute to these percentages. In not a single child did parents and teachers agree on the presence of clinically relevant behavioral problems.

Conclusions:(a) Behavioral problems are common in “epilepsy only,” but are not persistent. (b) Agreement between parent's and teacher's perceptions of behavior is low. (c) Behavioral problems are perceived to occur already in the earliest stage of the disease.
Modulation of Cortical Nitric Oxide Synthase, Glutamate, and Redox State by Nifedipine and Taurine in PTZ‐kindled Mice
Authors: El‐Abhar Hanan S. , El Gawad Hanan M. Abd
Published: March 2003

Summary: Purpose:Correlation between pentylenetetrazol (PTZ)‐induced kindling and the cortical nitric oxide synthase (NOS), intracellular calcium [Ca2+]i, glutamate, and free radicals was studied in mice, as well as the modulatory action of nifedipine and taurine on these parameters.

Methods:Male Swiss albino mice were used. Mice in one group received a single convulsive dose of PTZ (50 mg/kg, i.p), and were killed 24 h later. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 3 weeks. One kindled group was used as control, whereas two other groups were injected 30 min before PTZ with either nifedipine (30 mg/kg, i.p) or taurine (100 mg/kg, i.p). All three kindled groups were killed 24 h after the last injection.

Results:Compared with normal control group, PTZ‐kindled mice had significantly higher levels of [Ca2+]i, malonaldehyde (MDA), NOS, and lactate dehydrogenase (LDH) but had lower levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Acute seizures of the same intensity did not induce these alterations, indicating their link to the kindling phenomenon and not to seizure activity. The effect of taurine, known as an antioxidant, was more pronounced than that of the Ca2+‐channel blocker, nifedipine. The first drug reversed the PTZ‐kindled action on [Ca2+]i, NOS, LDH, GSH, and SOD, whereas nifedipine restored only LDH and GSH levels. However, both drugs did not restore the elevated MDA level.

Conclusions:This study suggests that free radicals, as well as NOS, are implicated in PTZ‐induced kindling, and that antioxidants could play a role in controlling the accompanying changes.
Stratifying Differences on Ictal/Interictal Subtraction SPECT Images
Authors: Koo Chi Wan , Devinsky Orrin , Hari Kim , Balasny Jennifer , Noz Marilyn E. , Kramer Elissa L.
Published: March 2003

Summary:  Purpose: Subtraction of interictal from ictal single‐photon emission computed tomography (SPECT) yields numerous foci that encompass a range of pixel values scattered in the brain. This preliminary study evaluated the significance of this range of values.

Methods: Subtraction images were obtained by registering, normalizing, and subtracting interictal from ictal SPECT for 13 patients. Pixel values of the resulting foci were divided into two groups: group I with 75–100% and group II with 50–75% of the maximal pixel value. Locations of these foci were determined, and concordance with surgical outcomes and scalp and invasive EEG findings was evaluated.

Results: In 10 of 13 cases, group I foci showed good concordance with ictal scalp EEG. In addition, group I foci corresponded well to invasive EEG findings in nine of 10 cases. Group I foci had bilateral distributions in seven of 13 cases. In 10 of 13 cases, group I foci corresponded well to regions of surgical resection. Of these 10 patients, nine showed good concordance with scalp EEG, eight showed good invasive EEG concordance, and eight were seizure free after resection. Conversely, group II foci had good concordance with ictal scalp EEG in only five of 13 cases, and invasive EEG findings, in only five of 10 cases. Group II foci had bilateral distributions in 10 of 13 cases. All 10 cases underwent unilateral surgical resections, and all had good surgical outcomes. In six of 13 cases, group II foci showed concordance with surgical sites. Of these six foci, four had poor concordance with scalp EEG, one had poor concordance with invasive EEG, and five had good surgical outcomes. Sensitivity and specificity for seizure localization of Group I foci were 40% and 88% respectively while sensitivity and specificity of Group II foci were 20% and 79% respectively.

Conclusions: Our data demonstrate that foci with 75–100% of maximal pixel values show good concordance with seizure foci, whereas foci of 50–75% may not. Therefore stratifying ictal/interictal differences may improve the specificity and localizing value of subtraction SPECT.
Coupling of Electrical and Metabolic Activity During Epileptiform Discharges
Authors: Heinemann U. , Buchheim K. , Gabriel S. , Kann O. , Kovács R. , Schuchmann S.
Published: March 2003

Summary: Changes in electrical activity, ionic microenvironments, and intracellular Ca concentration were measured during recurrent seizures induced by low Mg in slices and slice cultures. In both preparations, initial seizure‐like events (SLEs) changed after some time into drug‐refractory late recurrent discharges. In slice cultures, there was considerable cell loss in all hippocampal areas after 2 h of status epilepticus. During recurrent SLEs, the NAD(P)H autofluorescence declined, as did intramitochondrial calcium signals, indicating mitochondrial damage. At the same time, ethidium signals indicated increased radical oxygen species production. These alterations could be reduced by α‐tocopherol, which also protected slice cultures against status epilepticus–induced cell death.
Dendritic Targeting of mRNAs for Plasticity Genes in Experimental Models of Temporal Lobe Epilepsy
Authors: Simonato M. , Bregola G. , Armellin M. , Del Piccolo P. , Rodi D. , Zucchini S. , Tongiorgi E.
Published: March 2003

Summary:  Purpose: To analyze whether the subcellular localization of the messenger RNAs (mRNAs) coding for the neurotrophin brain‐derived neurotrophic factor (BDNF), its receptor TrkB, and the α and β subunits of calcium‐calmodulin–dependent kinase II (CaMKII) are modified after pilocarpine and kindled seizures.

Methods: Epilepsy models: pilocarpine and kindling. Analysis of mRNA levels in the dendrites: high‐resolution, nonradioactive in situ hybridization.

Results: Nonstimulated rats: BDNF, TrkB, and CaMKII‐β mRNAs localized in the soma and in the proximal dendrites of hippocampal pyramidal cells, and in the soma only of dentate gyrus (DG) granule cells; CaMKII‐α mRNA localized throughout the dendritic length in neurons of all hippocampal subfields. Pilocarpine seizures: increased staining levels of CaMKII‐α mRNA throughout the whole dendritic length in all hippocampal subfields; induction of CaMKII‐β, BDNF, and TrkB mRNAs dendritic targeting in CA1, CA3, and DG neurons. Class 2 kindled seizures: increase in dendritic staining intensity for CaMKII‐α in CA1, CA3, and DG neurons; induction of dendritic localization of CaMKII‐β, BDNF, and TrkB mRNAs in CA3 neurons. Fully kindled seizures: no change in the subcellular distribution of BDNF, TrkB and CaMKII‐β mRNAs; reduction of CaMKII‐α mRNA dendritic staining, as compared with unstimulated kindled animals.

Conclusions: Data provide evidence that BDNF, TrkB, and CaMKII‐α and ‐β mRNAs are accumulated in the dendrites of specific hippocampal neurons during pilocarpine seizures and kindling development. The dendritic targeting of these genes may be causally involved in epileptogenesis and thus may represent a new therapeutic target for some forms of partial epilepsy.
Neurotrophin Receptor Immunoreactivity in Severe Cerebral Cortical Dysplasia
Authors: Kim Joo‐Yong , Roh Jae‐Kyu , Lee Sang Kun , Chung Chun‐Kee
Published: March 2003

Summary:  Purpose: Cerebral cortical dysplasia (CD) is one of the important causes of intractable epilepsies and characterized histologically by disorganized cortical lamination and cytomegalic dysplastic neurons. Although it has been suggested that neurotrophins play an important role in differentiation, growth, and survival of developmental neurons, their pathogenetic role in CD has rarely been investigated.

Methods: To know the pathogenetic role of various neurotrophins on dysplastic neurons, immunohistochemical staining was performed using antibodies against NGFRp75, trkA, trkB, and trkC in surgical specimens of 20 patients with CD.

Results: TrkB and trkC were strongly expressed in dysplastic neurons of severe CD, and NGFRp75 was also expressed in some dysplastic neurons.

Conclusions: It is known that brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3) contribute to the differentiation of neuronal precursor cells, dendritic and axonal arborization, synaptic plasticity, and cellular hyperexcitability, so increased expression of trkB and trkC may have a critical pathogenetic role in cytoskeletal abnormalities and epileptogenicity in dysplastic neurons of CD.
Do Mossy Fibers Release GABA?
Authors: Walker Matthew C. , Ruiz Arnaud , Kullmann Dimitri M.
Published: March 2003

Purpose: Mossy fibers are the sole excitatory projection from dentate gyrus granule cells to the hippocampus, forming part of the trisynaptic hippocampal circuit. They undergo signficiant plasticity during epileptogenesis and have been implicated in seizure generation. Mossy fibers are a highly unusual projection in the mammalian brain; in addition to glutamate, they release adenosine, dynorphin, zinc, and possibly other peptides. Mossy fiber terminals also show intense immunoreactivity for the inhibitory neurotrasnmitter γ‐aminobutyric acid (GABA), and immunoreactivity for GAD67. The purpose of this review is to present physiologic evidence of GABA release by mossy fibers and its modulation by epileptic activity.

Methods: We used hippocampal slices from 3‐ to 5‐week‐old guinea pigs and made whole‐cell voltage clamp recordings from CA3 pyramidal cells. We placed stimulating electrodes in stratum granulosum and adjusted their position in order to recruit mossy fiber to CA3 projections.

Results: We have shown that electrical stimuli that recruit dentate granule cells elicit monosynaptic GABAA receptor–mediated synaptic signals in CA3 pyramidal neurons. These inhibitory signals satisfy the criteria that distinguish mossy fiber–CA3 synapses: high sensitivity to metabotropic glutamate‐receptor agonists, facilitation during repetitive stimulation, and N‐methyl‐D‐aspartate (NMDA) receptor–independent long‐term potentiation.

Conclusions: We have thus provided compelling evidence that there is a mossy fiber GABAergic signal. The physiologic role of this mossy fiber GABAergic signal is uncertain, but may be of developmental importance. Other evidence suggests that this GABAergic signal is transiently upregulated after seizures. This could have an inhibitory or disinhibitory effect, and further work is needed to elucidate its actual role.