bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumer Views on Management of Trigeminal Neuralgia
Authors: Zakrzewska J.M.
Published: March 2003

Objective.—To assess consumers' views on treatments used for trigeminal neuralgia and to compare their assessments with those of clinicians.

Methods.—A short self‐administered questionnaire was distributed to 133 individuals with trigeminal neuralgia and 21 clinicians attending national support group meetings in the United States and United Kingdom.

Results.—Responses were obtained from 82% of those with trigeminal neuralgia and from 50% of the clinicians. All sufferers had used medical therapies (mean of three drugs), and 40% to 50% had undergone surgical treatment. All of the attendees with trigeminal neuralgia reported at least one side effect (mean ± SD, 4.9 ± 1.8). The clinicians underestimated the number of side effects, but both groups agreed that drowsiness and cognitive impairment are side effects that are particularly disliked. The mean current quality‐of‐life score, measured on a scale of 1 to 5 (5 = worse), was 2.7 ± 1.5. Only 37% of sufferers gave an opinion as to the best form of treatment.

Conclusions.—Therapy leads to side effects which tend to be underestimated by clinicians. Patients currently find it difficult to make decisions about treatment. More collaborative research with active involvement of sufferers would improve the evidence base on which decisions can be made.
Sumatriptan Nasal Spray and Cognitive Function During Migraine: Results of an Open‐Label Study
Authors: Farmer Kathleen , Cady Roger , Bleiberg Joseph , Reeves Dennis , Putnam Gayla , O'Quinn Stephen , Batenhorst Alice
Published: March 2003

Objective.—To examine measures of cognitive function during acute migraine, before and after treatment with sumatriptan nasal spray, 20 mg.

Background.—Migraineurs frequently report symptoms of cognitive impairment during migraine. The efficacy of sumatriptan for treatment of migraine‐related cognitive impairment is undocumented.

Methods.—This open‐label, single‐attack study of 28 subjects used the Headache Care Center‐Automated Neuropsychological Assessment Metrics, a computerized neuropsychological assessment battery, to measure cognitive function under three patient conditions: migraine‐free, untreated migraine, and following sumatriptan (primary outcome). Headache response and pain‐free response, percent effectiveness, and clinical disability were measured.

Results.—Cognitive function (simple reaction time, sustained attention/concentration, working memory, visual‐spatial processing) and alertness/fatigue were adversely affected during migraine compared with migraine‐free performance (P<.05), and rapidly restored following sumatriptan nasal spray, 20 mg (P<.05). Headache and pain‐free response were 86% and 68%, respectively, at 135 minutes postdose. Changes in migraine pain severity, clinical disability, and percent effectiveness following treatment with sumatriptan nasal spray, 20 mg, were significantly correlated with cognitive function measures across all subtests (P<.001).

Conclusions.—Sumatriptan nasal spray, 20 mg, restored migraine‐related cognitive function and clinical disability.
Endothelin‐1 Plasma Levels in Cluster Headache
Authors: Franceschini R. , Tenconi G.L. , Leandri M. , Zoppoli F. , Gonella A. , Staltari S. , Barreca T.
Published: March 2003

Background and Objective.—A role for endothelin‐1, a potent vasoconstrictor peptide, in some cerebrovascular diseases has been proposed. To obtain preliminary data about peripheral concentrations of endothelin‐1 in acute cluster headache, we measured the plasma endothelin‐1 secretory pattern in 10 men with cluster during and independent of a headache attack.

Methods.—We collected blood samples for plasma endothelin‐1 determinations at 0, 15, 30, 45, 60, 90, and 120 minutes during a cluster attack and closely monitored blood pressures. We repeated the same sampling during an asymptomatic period.

Results.—The mean values of plasma endothelin‐1 (before a cluster headache, 3.3 ± 0.3 pg/mL) significantly increased (F = 2.578, P<.05) during an attack, reaching their peak at 30 minutes (5.0 ± 0.5 pg/mL, P<.05). We found no significant variations in mean arterial pressure.

Conclusion.—Endothelin‐1 may play a role in the pathophysiology of cluster attacks. The increase in plasma observed during cluster attacks may be linked to alterations in systemic hemodynamics and vascular tone.
Headache of Gastrointestinal Origin: Case Studies
Authors: Spierings Egilius L.H.
Published: March 2003

Three patients with headache of gastrointestinal origin are described. Reflux, dyspepsia, and constipation caused the headaches, which responded promptly to treatment of the respective gastrointestinal disorders.
Epidemiological and Clinical Characteristics of Migraine in Sivas, Turkey
Authors: Kececi Hulusi , Dener Sefik
Published: March 2003

Objective.—To investigate the epidemiology of migraine in Sivas, Turkey, including its prevalence, clinical characteristics, and impact according to age, sex, and socioeconomic status.

Methods.—Thirteen hundred twenty subjects were personally interviewed by a neurologist. Each household member with headache was asked questions regarding their headaches including age at onset, frequency, duration, character, location, severity, aggravating and ameliorating factors, and prodromal and associated symptoms. Migraine diagnoses were determined in accordance with the classification criteria of the International Headache Society.

Results.—Migraine was identified in 173 subjects (45 males and 128 females), and lifetime prevalence of migraine was 7.9% (95% CI, 5.66 to 10.1) in males and 17.1% (95% CI, 14 to 20) in females. Aura was reported by 1.4% of males and 3.3% of females.

Conclusion.—Migraine prevalence in Turkey is similar to that reported in Europe and the United States.
Platelet 3H Ketanserin Binding in Tension‐type Headache
Authors: Shukla R. , Husain M. , Tandon R. , Khanna V.K. , Nag D. , Dikshit M. , Srimal R.C. , Seth P.K.
Published: March 2003

Objective.—The present study was undertaken to investigate the alterations in platelet 5‐HT2 receptor binding in patients with tension‐type headache.

Background.—Serotonin (5‐HT) has an important but complex role in pain modulation. The involvement of serotonin in tension‐type headache has been investigated by studying serotonin in peripheral blood, but results have been inconclusive. There are, however, only a few investigations in which the status of platelet serotonin transporters has been studied by 3H imipramine and 3H paroxetine. The present study was undertaken to investigate alterations in platelet 5‐HT2A receptors using 3H ketanserin as a ligand.

Methods.—Platelet 3H ketanserin binding was studied in 14 patients with tension‐type headache and in 15 healthy controls. The binding characteristics, equilibrium dissociation constant and maximal number of binding sites were determined by Scatchard analysis.

Results.—There was no change in the equilibrium dissociation constant in the patients with headache as compared to the control group, but subgroup analysis revealed that patients with tension‐type headache with a headache index of less than 360 had a significantly lower equilibrium dissociation constant as compared to those with a headache index of more than 360; there was a significant correlation between the equilibrium dissociation constant and the headache index. A significant decrease was observed in the maximal number of binding sites in tension‐type headache. No correlation was observed between the maximal number of binding sites and age, duration of illness, or headache intensity.

Conclusions.—The findings of the present study show that there is a decrease in the number of binding sites of 5‐HT2A receptors in some patients with tension‐type headache, suggesting postsynaptic serotonergic dysfunction and the involvement of serotonin in that group.
Tolerability and Safety of Frovatriptan With Short‐ and Long‐term Use for Treatment of Migraine and in Comparison With Sumatriptan
Authors: Géraud Gilles , Spierings Egilius L.H. , Keywood Charlotte
Published: March 2003

Objective.—To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine.

Background.—Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range‐finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability.

Methods.—The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12‐month open‐label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24‐hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12‐lead electrocardiogram, hematology screen, and blood chemistry studies.

Results.—In the short‐term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12‐month study, 496 patients treated 13  878 migraine attacks. Frovatriptan was well tolerated in the short‐ and long‐term studies with 1% of patients in the short‐term studies and 5% of patients in the long‐term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan‐treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12‐lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment‐related serious adverse event.

Conclusions.—Short‐ and long‐term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg.
Corpora Amylacea REPIace the Hippocampal Pyramidal Cell Layer in a Patient with Temporal Lobe Epilepsy
Authors: Nishio Shunji , Morioka Takato , Kawamura Tadao , Fukui Kimiko , Nonaka Hiroki , Matsushima Michito
Published: March 2003

Summary: A 39‐year‐old woman, with a 23‐year history of medically intractable seizures of the complex partial type, underwent a left anterior temporal lobectomy and hippocampectomy. Histologic examinations revealed a massive occurrence of corpora amylacea, neuronal loss, and gliosis in the pyramidal cell layer of the hippocampus. The distribution of corpora amylacea in this case was quite distinctive and unlike the patterns of “nonspecific” corpora amylacea formation seen in aging or other neurodegenerative conditions. The pathogenetic aspects of the accumulation of these peculiar bodies are discussed in relation to hippocampal sclerosis.
Heart Rate and Heart Rate Variability Changes in the Intracarotid Sodium Amobarbital Test
Authors: Ahern Geoffrey L. , Sollers John J. , Lane Richard D. , Labiner David M. , Herring Anne M. , Weinand Martin E. , Hutzler Ronald , Thayer Julian F.
Published: March 2003

Summary:  Purpose: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re‐investigate this topic with a larger N than has heretofore been used.

Methods: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated.

Results: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA.

Conclusions: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.
Epilepsy in Estonia: A Quality‐of‐Life Study
Authors: Herodes Marju , Õun Andre , Haldre Sulev , Kaasik Ain‐Elmar
Published: March 2003

Summary: Purpose: To study the impact of epilepsy and its treatment on people with epilepsy in Estonia and to analyze how it is affected by the characteristics of epilepsy.

Methods: Clinical and demographic data about patients were obtained from medical notes and mailed self‐completed questionnaires (including the RAND 36‐Items Health Survey 1.0 (RAND‐36)).

Results: Information was collected from 203 patients aged 20–74 years, who all had active epilepsy. A third of the respondents had been seizure free during the last year. Eighty‐four percent were receiving monotherapy. More than half of respondents felt stigmatized by epilepsy, 24.7% of them highly so. A third were working full‐time, 31.9% were underemployed workers, and 11%, unemployed. Sixty‐two percent of these same unemployed or underemployed workers considered their epilepsy to be a significant reason for this situation. Overall, 44% believed they had been treated unfairly at work or when trying to get a job. Study respondents scored lower in all domains on the RAND‐36 than did persons from the control group. The biggest differences were found in five domains: Social functioning, Role limitations–physical, Role limitations–emotional, General health, and Vitality.

Conclusions: The clinical characteristics of this study were similar to those of most other series of prevalence cases of epilepsy. The level of employment among persons with epilepsy was not lower than that in the general population. The percentage of stigmatization was high. There were significant differences in the way respondents scored on the stigma scale and on the RAND‐36 domains when measuring their health status, depending above all on seizure frequency and type.
The Effects of Remifentanil on Epileptiform Discharges during Intraoperative Electrocorticography in Patients Undergoing Epilepsy Surgery
Authors: Wass C. Thomas , Grady Robert E. , Fessler A. James , Cascino Gregory D. , Lozada Leonard , Bechtle Perry S. , Marsh W. Richard , Sharbrough Frank W. , Schroeder Darrell R.
Published: March 2003

Summary:  Purpose: High‐dose i.v. opioids (e.g., alfentanil, 50 μg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra‐short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES.

Methods: After Institutional Review Board approval, 25 adult patients undergoing elective ECoG‐guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane 0.1% (end‐tidal) in 50% N2O, and i.v. fentanyl, 2 μg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 μg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one‐sided sign test; p values 0.05 were considered statistically significant.

Results: When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain.

Conclusions: During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half‐life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG‐guided ES.
Pregnancy Registries in Epilepsy
Authors: Beghi Ettore , Annegers John F. ,   for the Collaborative Group Pregnancy Registries in Epilepsy
Published: March 2003

Summary: The risk of major malformations in the offspring of mothers with epilepsy receiving antiepileptic drugs is 4–8% compared to 2–4% in the general population. Risk factors include daily dose and polytherapy. Selected drugs have been found to be associated with a higher risk of specific malformations (congenital heart defects and cleft palate with phenytoin and barbiturates; neural tube defects with valproate and carbamazepine). Although some of these findings are unquestionable, several questions are still unsolved, depending the characteristics of the target populations, the small samples of patients, and the design and limiting factors of the published reports. In the last decade, pregnancy registries have been activated by collaborative groups of physicians in Europe (EURAP), North America (NAREP), Australia and India (the latter two recently merged into EURAP), to enroll a large number of exposed women to be monitored prospectively with standardized methods, and by three pharmaceutical companies marketing lamotrigine, gabapentin and vigabatrin, as part of their post‐marketing surveillance. Even though the structure of these registries and the target populations should theoretically result in the identification of a sufficient number of women exposed to different drugs and examined for the occurrence of malformations of any type and severity, the implementation of a common database with information from the existing registries may provide valuable information in a shorter time period. Although differences between some of the registries limit the possibility to pool data, a gradual development of a collaboration is highly desirable to discuss a list of design issues and assess to what extent and how data could be compared and organized.
Felbamate Urolithiasis
Authors: Sparagana S. P. , Strand W. R. , Adams R. C.
Published: March 2003

Summary:  Purpose: To report a case of felbamate (FBM) urolithiasis.

Methods: Urographic imaging [sonography, abdominal computed tomography (CT), intravenous pyelogram, voiding cystourethrogram] and urologic procedures (cystoscopy with lithotripsy, ureteral stent) to define and capture the stones. Stone identification was by infrared spectroscopy and gas chromatography/mass spectrometry.

Results: A 15‐year‐old boy had painful hematuria, bilateral ureteral obstruction, and urinary retention. Kidney, bladder, and ureteral stones were found, and ureteral stent placement was required to relieve obstruction. The stone material was identified as FBM by chemical analysis. Stone formation ceased with discontinuation of FBM.

Conclusions: FBM urolithiasis can occur, and possible contributory factors include high felbamate dosage, drug polypharmacy, and risk factors for forming stones of other types. FBM urolithiasis may be heralded by crystalluria.
An Animal Model of Nonconvulsive Status Epilepticus: A Contribution to Clinical Controversies
Authors: Kršek Pavel , Mikulecká Anna , Druga Rastislav , Hliňák Zdeněk , Kubová Hana , Mareš Pavel
Published: March 2003

Summary:  Purpose: To characterize electroencephalographic and behavioral effects as well as electrophysiologic and morphologic consequences of a subconvulsive dose of pilocarpine in lithium chloride–pretreated rats.

Methods: Pilocarpine (15 mg/kg) was administered intraperitoneally to adult rats pretreated with lithium chloride (3 mEq/kg, i.p.). Behavior was observed for 2 h and videotaped in three consecutive sessions. At the same time, EEG was recorded from the sensorimotor cortex and the dorsal hippocampus. Threshold intensities of currents necessary to elicit hippocampal afterdischarges were determined 24 h and 1 week after the pilocarpine administration. The brains were histologically examined 1 week after pilocarpine administration using Nissl stain.

Results: Pilocarpine induced time‐limited nonconvulsive status epilepticus (NCSE). Epileptic EEG activity concurrent with prominent behavioral features was observed both in the neocortex and, predominantly, in the hippocampus. No changes in afterdischarge thresholds were observed in the dorsal hippocampus 24 h and 1 week after NCSE. One week after NCSE, seizure‐related brain damage was found mainly in the motor neocortical fields.

Conclusions: Pilocarpine‐induced NCSE in rats strongly resembles a short‐term human complex partial status epilepticus. Our animal model is suitable for studying the possible adverse effects of prolonged nonconvulsive seizures.
Placebos, Placebo Effect, and the Response to the Healing Situation: The Evolution of a Concept
Authors: Papakostas Yiannis G. , Daras Michael D.
Published: March 2003

Summary: In spite of its impressive progress, medicine has been strongly criticized for relying on its modern biomedical tradition to the neglect of the psychosocial aspects of health. This neglect may account for patients' dissatisfaction and eventual use of alternative health approaches. The concept of placebo has sustained dramatic “protean” metamorphoses through the ages. For centuries, placebos have been regarded as powerful deceptive therapies. From the middle of the twentieth century, however, conventional medicine has used placebos as methodologic tools to distinguish the specific from the nonspecific ingredients in treatments. In modern medical research, the double‐blind, placebo‐controlled, randomized clinical trial has been established as the gold standard for the assessment of any new treatment. Recently a new trend regarding placebos seems to have emerged. The placebo and other nonspecific effects elicited by the “healing situation” have been independently subjected to scientific study. Progress in this area may promote useful clinical applications, enabling physicians to broaden their perspectives on the healing process. We present the historical changes of the concept of placebo and the ethical issues raised by their use.
Oxcarbazepine in Focal Epilepsy and Hepatic Porphyria: A Case Report
Authors: Gaida‐Hommernick Bernadette , Rieck Karina , Runge Uwe
Published: March 2003

Summary:  Purpose: Despite the development of new antiepileptic agents (AEDs), the therapy of epilepsies along with hepatic porphyrias remains difficult. Most AEDs such as carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) may precipitate clinically latent porphyria by inducing hepatic metabolism and increasing hepatic heme synthesis. Actually, only gabapentin (GBP), an AED without any hepatic metabolism, is known as a potential therapy for partial seizures in patients having hepatic forms of porphyria.

Methods: We present the case of a 28‐year‐old man with porphyria cutanea tarda (PCT) who has had pharmacoresistant epilepsy with complex partial and secondarily generalized seizures since early childhood. Despite having undergone several AED therapies over the years, no seizure‐free interval had been observed. Only CBZ could cause a seizure reduction, but this treatment had to be discontinued as an elevation of the transaminases as well as pruritus and erythema were noted. The patient was then started on oxcarbazepine (OCBZ), a ketoanalogue of CBZ similar in its pharmacologic mechanism as well as its clinical use, but which, in contrast to CBZ, has only a low hepatic induction of microsomal enzymes. A final maintenance dose four times higher than that of CBZ was prescribed.

Results: In the follow‐up, the patient stopped having seizures, and his liver functions became normal.

Conclusions: It can be concluded that OCBZ can successfully be administered to patients with hepatic porphyria and focal epilepsy who did not respond to treatment with GBP.
Repeated Neural Tube Defects and Valproate Monotherapy Suggest a Pharmacogenetic Abnormality
Authors: Duncan Susan , Mercho Suha , Lopes‐Cendes Iscia , Seni Marie‐Helene , Benjamin Alice , Dubeau Francois , Andermann Frederick , Andermann Eva
Published: March 2003

Summary: Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.
The Importance of Drug Interactions in Epilepsy Therapy
Authors: Patsalos Philip N. , Fröscher Walter , Pisani Francesco , Van Rijn Clementina M.
Published: March 2003

Summary: Long‐term antiepileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to control seizures effectively, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. The fact that over‐the‐counter drugs and nutritional supplements are increasingly being self‐administered by patients also must be considered. Therefore the probability of patients with epilepsy experiencing drug interactions is high, particularly with the traditional AEDs, which are highly prone to drug interactions. Physicians prescribing AEDs to patients with epilepsy must, therefore, be aware of the potential for drug interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur both during combination therapy and on drug discontinuation. Although pharmacokinetic interactions are numerous and well described, pharmacodynamic interactions are few and usually concluded by default. Perhaps the most clinically significant pharmacodynamic interaction is that of lamotrigine (LTG) and valproic acid (VPA); these drugs exhibit synergistic efficacy when coadministered in patients with refractory partial and generalised seizures. Hepatic metabolism is often the target for pharmacokinetic drug interactions, and enzyme‐inducing drugs such as phenytoin (PHT), phenobarbitone (PB), and carbamazepine (CBZ) will readily enhance the metabolism of other AEDs [e.g., LTG, topiramate (TPM), and tiagabine (TGB)]. The enzyme‐inducing AEDs also enhance the metabolism of many other drugs (e.g., oral contraceptives, antidepressants, and warfarin) so that therapeutic efficacy of coadministered drugs is lost unless the dosage is increased. VPA inhibits the metabolism of PB and LTG, resulting in an elevation in the plasma concentrations of the inhibited drugs and consequently an increased risk of toxicity. The inhibition of the metabolism of CBZ by VPA results in an elevation of the metabolite CBZ‐epoxide, which also increases the risk of toxicity. Other examples include the inhibition of PHT and CBZ metabolism by cimetidine and CBZ metabolism by erythromycin. In recent years, a more rational approach has been taken with regard to metabolic drug interactions because of our enhanced understanding of the cytochrome P450 system that is responsible for the metabolism of many drugs, including AEDs. The review briefly discusses the mechanisms of drug interactions and then proceeds to highlight some of the more clinically relevant drug interactions between AEDs and between AEDs and non‐AEDs. Understanding the fundamental principles that contribute to a drug interaction may help the physician to better anticipate a drug interaction and allow a graded and planned therapeutic response and, therefore, help to enhance the management of patients with epilepsy who may require treatment with polytherapy regimens.
Relation between Responsiveness to Neurotransmitters and Complexity of Epileptiform Activity in Rat Hippocampal CA1 Neurons
Authors: Yang Hong‐Jun , Hu San‐Jue , Han Sheng , Liu Guo‐Peng , Xie Yong , Xu Jian‐Xue
Published: March 2003

Summary:  Purpose: Our previous works suggested that sensitivity of neurons with chaotic firing patterns to stimuli is significantly greater than that in neurons with periodic firing patterns, which shows that responsiveness of neurons may depend on the complexity of the firing series. This study was performed to determine the relation between responsiveness of the hippocampal CA1 neurons with epileptiform activity (EA) to neurotransmitters and their complexity of firing series.

Methods: Firing series of CA1 neurons were recorded extracellularly in rat hippocampal slice. Approximate entropy was used to describe the complexity of the interspike interval (ISI) series. EA was induced by local application of penicillin (1,000 IU/ml). The change of firing rate induced by neurotransmitters (glutamate and γ‐aminobutyric acid) was compared with that of the degree of complexity of ISI series in the process of EA.

Results: The excitatory responses to glutamate and the inhibitory responses to γ‐aminobutyric acid in CA1 neurons appeared to be decreased during the process of penicillin‐induced EA. However, during this same process, the approximate entropy of the ISI series also was decreased significantly.

Conclusions: The results suggest that the reduced responses to neurotransmitters of the CA1 neurons appear to be closely related to the onset of EA. Furthermore, these neurons show that the changes in responsiveness are closely parallel to the decrease of degree of complexity of firing series during penicillin epileptogenesis.
Altered Flurothyl Seizure Induction Latency, Phenotype, and Subsequent Mortality in a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis/Batten Disease
Authors: Kriscenski‐Perry Elizabeth , Applegate Craig D. , Serour Andrew , Mhyre Timothy R. , Leonardo Christopher C. , Pearce David A.
Published: March 2003

Summary:  Purpose: Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is a pediatric neurodegenerative disease characterized by vision loss, seizure activity, cognitive decline, and premature death. Discovery of the Batten disease–related gene, CLN3, led to creation of a Cln3 protein‐deficient mouse model (Cln3−/−), which recapitulates some of the histopathologic characteristics of the human condition. We hypothesized that lack of Cln3 would alter seizure‐related behavioral parameters.

Methods: Using flurothyl gas inhalation, we examined seizure‐induction latencies in Cln3−/− mice and wildtype (wt) controls at time points that represent late neonatal, immature, mature, and aged time points. We examined latency to first myoclonic jerk (LMJ), latency to loss of posture (LOP), and subsequent mortality.

Results: Our results demonstrate an age‐dependent alteration of seizure‐induction latencies in Cln3−/−. Immature Cln−/− mice aged 35–42 days had an increased latency to both LMJ and LOP compared with age‐matched wt controls. There were no significant latency differences between Cln3−/− and wt at other time points examined. Mortality after generalized seizure was high in both Cln3−/− and wt animals at late neonatal and immature developmental stages. No mortality was seen in wt mice past maturity at 6 weeks. Mature and aged Cln3−/− animals retained a vulnerability to death after seizure activity.

Conclusions: These results suggest that a deficiency of Cln3 protein in the Batten model mice may result in age‐dependent alteration of the neuroanatomic and biochemical substrates involved in seizure propagation and recovery. This may be important in understanding seizures, neurodegeneration, and premature death in human Batten disease.
Visual Field Constriction in 91 Finnish Children Treated with Vigabatrin
Authors: Vanhatalo Sampsa , Nousiainen Iiris , Eriksson Kai , Rantala Heikki , Vainionpää Leena , Mustonen Kirsi , Äärimaa Tuula , Alen Reija , Aine Marjo‐Riitta , Byring Roger , Hirvasniemi Aune , Nuutila Auli , Walden Tiina , Ritanen‐Mohammed Ulla‐Maija , Karttunen‐Lewandowski Pirkko , Pohjola Leena‐Maria , Kaksonen Satu , Jurvelin Pekka , Granström Marja‐Liisa
Published: March 2003

Summary:  Purpose: To study the prevalence and features of visual field constrictions (VFCs) associated with vigabatrin (VGB) in children.

Methods: A systematic collection of all children with any history of VGB treatment in fifteen Finnish neuropediatric units was performed, and children were included after being able to cooperate reliably in repeated visual field tests by Goldmann kinetic perimetry. This inclusion criterion yielded 91 children (45 boys; 46 girls) between ages 5.6 and 17.9 years. Visual field extent <70 degrees in the temporal meridian was considered abnormal VFC.

Results: There was a notable variation in visual field extents between successive test sessions and between different individuals. VFCs <70 degrees were found in repeated test sessions in 17 (18.7%) of 91 children. There was no difference in the ages at the study, the ages at the beginning of treatment, the total duration of the treatment, general cognitive performance, or neuroradiologic findings between the patients with normal visual fields and those with VFC, but the patients with VFC had received a higher total dose of VGB. In linear regression analysis, there were statistically significant inverse correlations between the temporal extent of the visual fields and the total dose and the duration of VGB treatment. The shortest duration of VGB treatment associated with VFC was 15 months, and the lowest total dose 914 g.

Conclusions. Because of a wide variation in normal visual‐field test results in children, the prevalence figures of VFCs are highly dependent on the definition of normality. Although our results confirm the previous findings that VFC may occur in children treated with VGB, our study points out the need to reevaluate critically any suspected VFC to avoid misdiagnosis. Nevertheless, our study suggests that the prevalence of VFC may be lower in children than in adults, and that the cumulative dose of VGB or length of VGB therapy may add to the personal predisposition for developing VFC.
Anticonvulsant Profile and Teratogenicity of N‐methyl‐tetramethylcyclopropyl Carboxamide: A New Antiepileptic Drug
Authors: Isoherranen Nina , White H. Steve , Finnell Richard H. , Yagen Boris , Woodhead José H. , Bennett Gregory D. , Wilcox Karen S. , Barton Matthew E. , Bialer Meir
Published: March 2003

Summary:  Purpose: The studies presented here represent our efforts to investigate the anticonvulsant activity of N‐methyl‐tetramethylcyclopropyl carboxamide (M‐TMCD) and its metabolite tetramethylcyclopropyl carboxamide (TMCD) in various animal (rodent) models of human epilepsy, and to evaluate their ability to induce neural tube defects (NTDs) and neurotoxicity.

Methods: The anticonvulsant activity of M‐TMCD and TMCD was determined after intraperitoneal (i.p.) administration to CF#1 mice, and either oral or i.p. administration to Sprague–Dawley rats. The ability of M‐TMCD and TMCD to block electrical‐, chemical‐, or sensory‐induced seizures was examined in eight animal models of epilepsy. The plasma and brain concentrations of M‐TMCD and TMCD were determined in the CF#1 mice after i.p. administration. The induction of NTDs by M‐TMCD and TMCD was evaluated after a single i.p. administration at day 8.5 of gestation in a highly inbred mouse strain (SWV) that is susceptible to valproic acid–induced neural tube defects.

Results: In mice, M‐TMCD afforded protection against maximal electroshock (MES)‐induced, pentylenetetrazol (Metrazol)‐induced, and bicuculline‐induced seizures, as well as against 6‐Hz “psychomotor” seizures and sound‐induced seizures with ED50 values of 99, 39, 81, 51, and 10 mg/kg, respectively. In rats, M‐TMCD effectively prevented MES‐ and Metrazol‐induced seizures and secondarily generalized seizures in hippocampal kindled rats (ED50 values of 82, 45, and 39 mg/kg, respectively). Unlike M‐TMCD, TMCD was active only against Metrazol‐induced seizures in mice and rats (ED50 values of 57 and 52 mg/kg, respectively). Neither M‐TMCD nor TMCD was found to induce NTDs in SWV mice.

Conclusions: The results obtained in this study show that M‐TMCD is a broad‐spectrum anticonvulsant drug that does not induce NTDs and support additional studies to evaluate its full therapeutic potential.
New Zealand Community Attitudes toward People with Epilepsy
Authors: Hills Michael D. , MacKenzie Hamish C.
Published: March 2003

Summary:  Purpose: International surveys on knowledge and attitudes toward people with epilepsy suggest that public opinion is improving in many countries. This study aimed to discover how New Zealand compared with other countries, and how subgroups within the New Zealand population compared with each other, by conducting a survey of community knowledge and attitudes toward epilepsy.

Methods: Telephone interviews were conducted on a random sample of 400 persons older than 17 years, drawn from a mid‐sized provincial town and its hinterland.

Results: Ninety‐five percent of respondents had heard or read about epilepsy; 73% knew someone with epilepsy; and 67% had seen an epileptic seizure. Somewhat less knowledgeable were young people, the less educated, lower socioeconomic status (SES), and those of Maori or non‐European ethnicity. Attitudes toward people with epilepsy were favorable, with only 5% objecting to their child marrying a person who sometimes had seizures. Less‐positive attitudes were found among some older people.

Conclusions: Compared with those in other Western countries, New Zealanders are well informed about epilepsy, and their attitudes toward it are mainly positive. Continuing public education about epilepsy is still necessary, especially among the young, the non‐European, and older people.
Detection and Localization of Focal Cortical Dysplasia by Voxel‐based 3‐D MRI Analysis
Authors: Kassubek Jan , Huppertz Hans‐Jürgen , Spreer Joachim , Schulze‐Bonhage Andreas
Published: March 2003

Summary:  Purpose: Focal cortical dysplasia (FCD) is a frequent cause of partial epilepsy. Its diagnosis by visual evaluation of magnetic resonance images (MRIs) remains difficult. The purpose of this study was to apply a novel automated and observer‐independent voxel‐based technique for the analysis of 3‐dimensional (3‐D) MRI to detect and localize FCD.

Methods: The technique was based on algorithms of the SPM99 software and included the spatial normalization of 3‐D MRI data sets to a common stereotaxic space and the segmentation of cortical grey matter. The resulting data sets represented grey‐matter density maps where each voxel encoded the grey‐matter concentration at the corresponding position in the original MRI. A normal database was set up by calculating and averaging the grey‐matter density maps of 30 healthy volunteers. The MRI data sets of seven epilepsy patients with FCD were evaluated retrospectively for dysplastic lesions by voxelwise subtraction of the mean grey‐matter density map of the normal database and searching automatically for local and global maxima in the resulting data set.

Results: In all patients, the results of voxel‐based 3‐D MRI analysis corresponded both to the location of the dysplastic lesions in conventional MRI and to seizure semiology and EEG findings. In one case, surgery was performed, and the diagnosis FCD was supported by histology.

Conclusions: The technique of voxel‐based 3‐D MRI analysis and comparison with a normal database seems to provide a valuable additional screening tool for the detection of FCD.
The Experience of Earthquakes by Patients with Epileptic and Psychogenic Nonepileptic Seizures
Authors: Watson Nathaniel F. , Doherty Michael J. , Dodrill Carl B. , Farrell Don , Miller John W.
Published: March 2003

Summary:  Purpose: We sought to understand better the experience of seizures by studying differences in the subjective experience of being in an earthquake between patients with epileptic (EP) and nonepileptic (NES) seizures.

Methods: Forty‐eight patients with CCTV/EEG‐documented EP or NES who were in the Seattle metropolitan area during the February 28, 2001 Nisqually earthquake were randomly selected for telephone interviews on their earthquake experiences, including whether they thought they were having a seizure during the event.

Results: Twenty‐three percent of EP patients spontaneously volunteered that they initially thought they were having a seizure during the earthquake as compared with none of the NES individuals (p = 0.03). However, 35% of EP and 23% of NES patients thought they were having a seizure during it when asked directly (p = 0.37). The most common reasons given, regardless of seizure type, were shaking and feelings of losing control. Of those responding negatively, 100% of EP and 47% of NES patients said that movement of their environment indicated that it was not a seizure (p = 0.001). EP patients took an average of 42 s to realize that the earthquake was not a seizure compared with 105 s for the NES group (p = 0.06). The earthquake precipitated seizures in both groups (11.5% EP, 9.1% NES).

Conclusions: EP patients were more likely to mistake the earthquake spontaneously for a seizure. This indicates these two experiences are similar and provides a glimpse into the subjective experience of a seizure for those who have never had one but have experienced an earthquake.
Valproate‐induced Encephalopathy: Assessment with MR Imaging and 1H MR Spectroscopy
Authors: Ziyeh Sargon , Thiel Thorsten , Spreer Joachim , Klisch Joachim , Schumacher Martin
Published: March 2003

Summary: The anticonvulsant agent valproate (VPA) may cause hyperammonemic encephalopathy. Magnetic resonance imaging (MRI) and proton MR spectroscopic (MRS) findings in a patient with VPA‐induced hyperammonemic encephalopathy are described. MRI showed a metabolic–toxic lesion pattern with bilateral T2‐hyperintense lesions in the cerebellar white matter and in the globus pallidus. MR spectroscopic findings were indistinguishable from hepatic encephalopathy with severe depletion of myoinositol and choline and with glutamine excess. N‐Acetylaspartate levels were moderately decreased. Quantitative MRS gave detailed insight into alterations of brain metabolism in VPA‐induced encephalopathy.
Dissociative and Associated Psychopathological Symptoms in Patients with Epilepsy, Pseudoseizures, and Both Seizure Forms
Authors: Prueter Christian , Schultz‐Venrath Ulrich , Rimpau Wilhelm
Published: March 2003

Summary:  Purpose: A controversy currently exists regarding the significance of dissociation and conversion in the pathogenesis of pseudoepileptic seizures. After the abolition of the term “hysterical neurosis” from the current diagnostic systems, these seizures were diagnosed as either Dissociative Disorders (ICD‐10) or in the DSM IV as Somatoform disorder, most often of conversion type. Recent studies of patients with Dissociative Disorders found that most patients also had conversion symptoms.

Methods: In the present study, 60 patients of an outpatient clinic for epilepsy were assessed for the presence of dissociative symptoms and general psychopathologic symptoms by using the German version of the Dissociative Experience Scale (DES) and the Symptom Check List (SCL‐90‐R).

Results: The patients with pseudoepileptic seizures showed a significantly higher incidence of dissociation (p < 0.0098) and general psychopathologic symptoms (p < 0.0083). Depression, anxiety, and obsession were dominating psychopathologic symptoms in all patients.

Conclusions: The significantly higher incidence of dissociation in the patients with pseudoepileptic seizures suggests dissociation in the pathogenesis of these seizures.
Topiramate in Patients with Learning Disability and Refractory Epilepsy
Authors: Kelly Kevin , Stephen Linda J. , Sills Graeme J. , Brodie Martin J.
Published: March 2003

Summary:  Purpose: Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre.

Methods: Sixty‐four patients (36 men, 28 women, aged 16–65 years) were begun on adjunctive TPM after a 3‐month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6‐month period at optimal TPM dosing. These were seizure freedom or ≥50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study.

Results: Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on ≤200 mg daily. Mean carer scores did not worsen with TPM therapy.

Conclusions: TPM was effective as add‐on therapy in learning‐disabled people with difficult‐to‐control epilepsy. Seizure freedom is a realistic goal in this population.
Role of the Superior Colliculus and the Intercollicular Nucleus in the Brainstem Seizure Circuitry of the Genetically Epilepsy‐prone Rat
Authors: Merrill Michelle A. , Clough Richard W. , Jobe Phillip C. , Browning Ronald A.
Published: March 2003

Summary:  Purpose: The neuronal network responsible for the convulsive behavior associated with sound‐induced seizures in genetically epilepsy‐prone rats (GEPRs) is believed to include the inferior colliculus and other brainstem structures such as the deep layers of the superior colliculus (DLSC), periaqueductal gray, and pontine reticular formation. However, previous studies also suggested that the DLSC and the nearby intercollicular nucleus (ICN) are part of a midbrain anticonvulsant zone capable of suppressing tonic convulsions when activated with bicuculline. Our aim in this study was to investigate the role of the superior colliculus (SC) and the ICN in generalized tonic–clonic seizures (GTCSs).

Methods: Bilateral lesions of the SC and the ICN as well as bicuculline infusions into the ICN were used to assess the role of this dorsal midbrain region in brainstem seizures induced by sound stimulation in GEPR‐9s and GEPR‐3s.

Results: Lesions of the SC markedly attenuated audiogenic seizure (AGS) severity by abolishing all behavioral components except the wild running. Lesions of the ICN significantly reduced seizure severity in GEPR‐9s, but were somewhat less effective than SC lesions. Bicuculline infusion into the deep layers of the SC and/or the ICN produced audiogenic‐like seizures in GEPR‐9s.

Conclusions: These findings support the hypothesis that the SC and ICN are important components of the brainstem seizure network, but suggest they are not necessary for the wild‐running component of the seizure. The results further indicate that stimulation of the tectum facilitates GTCSs. Thus these findings suggest that the dorsal midbrain, when stimulated, is proconvulsant rather than anticonvulsant regarding brainstem seizures in GEPRs.