bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsant Activity of PNU‐151774E1 in the Amygdala Kindled Model of Complex Partial Seizures
Authors: Maj Roberto , Fariello Ruggero G. , Pevarello Paolo , Varasi Mario , McArthur Robert A. , Salvati Patricia
Published: August 2005

Summary: Purpose: PNU‐151774E [(S)‐(+)‐2‐(4‐(3‐fluoro‐benzyloxy) benzylamino) propanamide, methanesulfonate] is a novel antiepileptic drug (AED) with a broad spectrum of activity in a variety of chemically and mechanically induced seizures. The objective of this study was to evaluate the activity of PNU‐151774E in the amygdala fully kindled rat model of complex partial seizures, and to compare its effects with those of carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), and gabapentin (GBP), drugs used to treat this disease state.

Methods: Male Wistar rats were stimulated daily through electrodes implanted in the amygdala with a threshold current until fully generalized seizures developed. The rats were then treated with various doses of a single compound. Control values for each rat and drug dose were determined after vehicle administration followed by electrical stimulation 1 day before drug treatment.

Results: PNU‐151774E (1, 10, 30 mg/kg; i.p.) reduced the duration of behavioral seizures significantly and dose‐dependently at doses starting from 1 mg/kg. Higher doses significantly reduced seizure severity and afterdischarge duration. In contrast, no dose‐related effects were noted after administration of PHT, whereas after CBZ treatment, a plateau of activity was noted from the intermediate to higher doses. The effects of PNU‐151774E were comparable to those of LTG and GBP.

Conclusions: The activity shown by PNU‐151774E at doses similar to those that are active in models of generalized seizures indicates that PNU‐151774E would also have potential efficacy in the treatment of complex partial seizures.
Bidirectional Transfer Between Electrical and Flurothyl Kindling in Mice: Evidence for Common Processes in Epileptogenesis
Authors: Ferland Russell J. , Applegate Craig D.
Published: August 2005

Summary: Purpose: This study sought to determine whether there was a transfer of seizure susceptibility between two models of epileptogenesis, electrical kindling and a newly described model of flurothyl kindling. In this study, we determined the effects of preexposure to one kindling agent on the seizure responsiveness to the other.

Methods: Mice were divided into three groups: (a) six mice (FLK) were kindled with flurothyl, rechallenged with flurothyl after a 28‐day incubation phase, implanted with olfactory bulb (OB) electrodes, and electrically kindled; (b) six mice (ELK) were implanted with OB electrodes, electrically kindled to six stage 5 seizures, and given one flurothyl trial 3 days later and a second flurothyl trial after a 28‐day incubation period; and (c) six mice (IMP) were implanted with OB electrodes, tested with flurothyl at the same times as the ELK group, and later electrically kindled.

Results: Mice that were previously kindled with flurothyl (FLK) had significantly faster electrical kindling rates to one stage 5 seizure or to six stage 5 seizures compared with animals in the ELK and IMP groups. Mice that were previously exposed to either electrical kindling or flurothyl kindling had significantly diminished latencies to generalized seizure onset (flurothyl‐induced seizure thresholds) either before or after a 28‐day incubation period compared with the IMP control mice. In addition, both the FLK and ELK groups had significantly increased percentages of mice expressing forebrain—brainstem seizures, compared with the IMP group, following either rechallenge with flurothyl after a 28‐day incubation or focal electrical kindling.

Conclusions: These findings indicate a near‐complete bidirectional transfer between these electrical and flurothyl kindling models. Mice that were previously exposed to either electrical or flurothyl kindling have increased seizure susceptibilities and altered seizure phenotypes when exposed to the other seizure paradigm. Overall, these studies indicate that previous seizures are the critical determinant of the bidirectional transfer of seizure susceptibility observed, and not the electrical or pharmacologic properties of the original kindling agent. Finally, the observation of near identity in transfer characteristics between electrical and flurothyl kindling models suggests that the proepileptogenic processes initiated by exposure to either model are similar.
Antiepileptic Drug Therapy and Sexual Function in Men with Epilepsy
Authors: Duncan Susan , Blacklaw Jackie , Beastall G. H. , Brodie M. J.
Published: August 2005

Summary: Purpose: To study the effects of antiepileptic drugs (AEDs) on sex hormone levels and sexual activity in a group of men attending a hospital‐based epilepsy clinic.

Methods: One hundred eighteen men being treated with AED therapy, 32 with epilepsy but not receiving AEDs, and 34 controls were recruited. All subjects were aged 18–65 years. Blood (20 ml) was removed for hormone assays, after which each subject completed a validated questionnaire [Sexuality Experience Scores (Frenken and Vennix, 1981)] aimed at exploring the individuals' sexual activity and attitudes to sexual morality.

Results: Men taking carbamazepine (CBZ) only had significantly higher mean sex hormone‐binding globulin (SHBG) levels than the control group. The CBZ group also had a significantly lower mean DHEAS concentration than the control, untreated, and sodium valproate (VPA) monotherapy groups. The phenytoin monotherapy group (PHT) had a significantly higher mean SHBG than both the control and untreated groups, and had a significantly higher mean total testosterone (TT) value than the control untreated, CBZ, and VPA groups, and a significantly lower mean DHEAS than the controls, untreated, and VPA groups. Men receiving more than one AED had significantly higher mean SHBG concentrations compared with control, untreated, and VPA groups. In addition, the poly‐therapy group's mean TT was significantly higher than the control and VPA groups, although its mean DHEAS concentration was lower than the control, untreated, and VPA groups. There were no significant differences between the study groups in mean FT, Budrostenedione (AND), or estradiol levels. But the CBZ, PHT, and polytherapy groups had significantly lower mean free and rogen index (FAI) than the controls. The CBZ group had a lower mean FAI than the VPA group. The poly‐therapy group had a lower FAI than the untreated group. Sexuality Experience Scores (SES) showed that those men receiving AEDs embraced a stricter sexual morality than the controls and untreated, and expressed greater satisfaction with their marriages than the control and untreated groups.

Conclusions: Seizure type did not affect SES scores. Multiple regression showed men who had received further education were less accepting of strict sexual morality.
Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence Reviewed
Authors: Deckers Charles L. P. , Czuczwar Stanislaw J. , Hekster Yechiel A. , Kewser Antoine , Kubova Hana , Meinardi Harry , Patsalos Philip N. , Renier Willy O. , Van Rijn Clementina M.
Published: August 2005

Summary: Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches.

Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers.

Results: Thirty‐nine papers were identified reporting on two‐drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point.

Conclusions: There is evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with an NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy.
Renal Tubular Function in Patients Receiving Anticonvulsant Therapy: A Long‐Term Study
Authors: Verrotti A. , Greco R. , Pascarella R. , Matera V. , Morgese G. , Chiarelli F.
Published: August 2005

Summary: Purpose: The goal of the study was to evaluate the tubular renal function in children and adolescents who are undergoing monotherapy with sodium valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB).

Methods: The urinary excretion of N‐acetyl‐β‐glucosaminidase (NAG), β‐galactosidase (β‐Gal), alanine‐amino‐peptidase (AAP), and α1‐microglobulin (α1M) was measured in 58 epileptic patients (29 girls and 29 boys), aged 12.6 ± 3.9 years, who were subdivided into three groups according to their therapy. Fifty healthy sex‐ and age‐matched children served as controls. The measurements were taken before the beginning of therapy and after 6 months, 1 year, and 2 years of therapy.

Results: Before the beginning of therapy, there were no significant differences in NAG, β‐Gal, AAP, and α1M values between the control group and the three groups of epileptic children. After 6 months of therapy, patients treated with VPA and CBZ showed a significant increase in the urinary excretion of NAG and β‐Gal compared with baseline data and control values. After 1 and 2 years, these patients showed a persistence of the changes found after 6 months of therapy. In patients treated with PB, we did not find any significant variation in NAG, β‐Gal, AAP, and α1M urinary excretion.

Conclusions: Our study demonstrates that in patients treated with VPA and CBZ, an impairment of tubular function can be present, whereas PB does not cause any significant change.
Expression of 5α‐Reductase and 3α‐Hydroxisteroid Oxidoreductase in the Hippocampus of Patients with Chronic Temporal Lobe Epilepsy
Authors: Stoffel‐Wagner B. , Beyenburg S. , Watzka M. , Blümcke I. , Bauer J. , Schramm J. , Bidlingmaier F. , Elger C. E.
Published: August 2005

Summary: Purpose: The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroen‐docrine conversion of progesterone appears to be 5α‐reduction and 3α‐hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3α,5α‐tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5α‐reductase and 3α‐hydroxysteroid oxidoreductase (3α‐HSOR), we studied the expression of 5α‐reductase types 1 and 2 and 3α‐HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy.

Methods: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription‐polymerase chain reaction (RT‐PCR).

Results: 5α‐Reductase 1 mRNA and 3α‐HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5α‐reductase 2 mRNA and 3α‐HSOR 1 mRNA were not expressed. Neither 5α‐reductase 1 mRNA nor 3α‐HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults.

Conclusions: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5α‐reductase and the type 2 isozyme of 3α‐HSOR in the human hippocampus. The finding that both 5α‐reductase and 3α‐HSOR are present in the hippocampus leads us to assume the synthesis of neuro‐active steroids in this human brain area.
The Potential for Vigabatrin‐Induced Intramyelinic Edema in Humans
Authors: Cohen Jeffrey A. , Fisher Robert S. , Brigell Mitchell G. , Peyster Robert G. , Sze Gordon
Published: August 2005

Summary: Purpose: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species.

Methods: Animal and human data were reviewed with respect to the potential for VGB‐induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for <15 years to identify patients developing clinical abnormalities that might be IME related.

Results: The histologic lesions of VGB‐induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI). Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear‐cut IME‐related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB‐treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient‐years of VGB exposure (‐175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB‐induced IME has been identified.

Conclusions: Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.
The Value of Early Postictal EEG in Children with Complex Febrile Seizures
Authors: Maytal J. , Steele R. , Eviatar L. , Novak G.
Published: August 2005

Summary: Purpose: To assess the usefulness of an early post‐ictal EEG in neurologically normal children with complex febrile seizures.

Methods: We conducted a retrospective chart review of all neurologically normal children who were hospitalized over a period of 2.5 years after complex febrile seizures, and had an EEG up to 1 week after the seizure.

Results: Thirty‐three patients (mean age, 17.8 months) qualified for inclusion into the study. Twenty‐four patients were qualified as complex cases based on one factor (prolonged in 9, repetitive in 13, and focal in 2). Nine other patients had two complex factors: in six patients, the seizures were long and repetitive; in two patients, the seizures were focal and repetitive; and in one patient, the seizures were long, focal, and repetitive. Thirteen (39%) patients experienced prior febrile seizures. All 33 patients had a normal postictal sleep EEG. Our results indicate with a 95% probability that the true rate of abnormalities in an early postictal EEG performed on otherwise normal children with complex febrile seizures is 8.6% or less.

Conclusions: The yield of abnormalities of an early postictal EEG in this population is low and similar to the reported rate of abnormalities in children with simple febrile seizures. The routine practice of obtaining an early EEG in neurologically normal children with complex febrile seizures is not justified.
Seizures in Rural Zambia
Authors: Birbeck Gretchen L.
Published: August 2005

Summary: Purpose: To describe the period prevalence of epilepsy and febrile seizures in a bush hospital and discuss the medical sequelae and social impact of seizures in this population.

Methods: For 13 weeks, an evaluation of inpatients was made at Chikankata Hospital in rural Zambia. Inpatients identified as having seizures, “fits,”“spells,” or “fainting,” were evaluated by a medical records review, basic demographic data, a neurological history and physical examination, and a treatment history. A semistructured questionnaire was administered to evaluate the social impact of seizures and assess factors associated with delayed care seeking.

Results: Seizures composed 44% of all inpatient neurologic disease and resulted in 84 admissions. Epilepsy patients received treatment primarily from traditional healers; only 31% reported ever receiving antiepileptic drugs (AEDs). Among those who had received treatment, AEDs were frequently underdosed. Patients with epilepsy had significantly less education than their sex‐matched siblings. Patients with untreated epilepsy for >2 years were more likely to have experienced serious burns or falls requiring hospitalization. Children with febrile seizures whose parents held supernatural beliefs regarding seizures were more likely to be treated with traditional medicines, had higher malarial parasite counts, and required longer hospitalizations than children with febrile seizures whose parents recognized the association between seizures and hyperthermia.

Conclusions: Epilepsy and febrile seizures are responsible for a significant burden of disease in rural Zambia. Serious medical complications often result from seizures, especially if untreated for >2 years. Social stigma decreases educational opportunities and misperceptions regarding seizures may result in delayed care for children with febrile seizures. Some evidence suggests that epilepsy is underreported, underrecognized, and undertreated in this population.
Prognostic Factors Affecting Long‐Term Retention of Topiramate in Patients with Chronic Epilepsy
Authors: Lhatoo S. D. , Wong I. C. K. , Sander J. W. A. S.
Published: August 2005

Summary:Purpose: To determine the long‐term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention.

Methods: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan‐Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression.

Results: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy.

Conclusions: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.
Bilateral Periventricular and Subcortical Heterotopia in a Man with Refractory Epilepsy
Authors: Sisodiya S. M. , Free S. L. , Duncan J. S. , Stevens J. M.
Published: August 2005

Summary: Purpose: To report a novel malformation in a male subject with refractory partial seizures.

Methods: Magnetic resonance imaging (MRI) and data reformatting in a subject referred for management of partial seizures.

Results: The patient had four distinct partial seizure types, without learning disability. MRI demonstrated the novel association of bilateral laminar subcortical heterotopia, bilateral temporal periventricular heterotopia, and hippocampal malformation.

Conclusions: This previously unreported complex bilateral neocortical and archicortical malformation in a male patient cannot be explained by known genetic causes of heterotopia, raising the possibility of a novel gene involved in brain formation.
Oxygen Desaturations Triggered by Partial Seizures: Implications for Cardiopulmonary Instability in Epilepsy
Authors: Blum Andrew S. , Ives John R. , Goldberger Ary L. , Al‐Aweel Issa C. , Krishnamurthy K. B. , Drislane Frank W. , Schomer Donald L.
Published: August 2005

Summary: Purpose: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal‐associated hypoxemia.

Methods: During long‐term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity.

Results: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (±SD) was 73 ± 18 s. Mean Spo2 desaturation duration was 76 ± 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 ± 16 s. Mean (±SD) Spo2 nadir was 83 ± 5% (range, 77–91%), occurring an average of 35 ± 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations.

Conclusions: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.
EKG Abnormalities During Partial Seizures in Refractory Epilepsy
Authors: Nei Maromi , Ho Reginald T. , Sperling Michael R.
Published: August 2005

Summary: Purpose: This study assessed the frequency and character of ictal cardiac rhythm and conduction abnormalities in intractable epilepsy. Sudden unexpected death in epilepsy (SUDEP) is a major cause of excess mortality in people with refractory epilepsy, and cardiac arrhythmias during seizures may be responsible. The frequency of cardiac abnormalities during seizures in patients with refractory epilepsy must be determined.

Methods: Fifty‐one seizures in 43 patients with intractable partial epilepsy were analyzed prospectively from CCTV‐EEG monitoring with one ECG channel. Arrhythmias, repolarization abnormalities, and PR and QTC intervals were determined for preictal (3 min), ictal, and postictal (3 min) periods for one or more seizures per patient. Parametric statistics were used for continuous variables, and nonparametric statistics were used for categoric variables.

Results: Of the patients, 39% had one or more abnormalities of rhythm and/or repolarization during or immediately after seizures. Abnormalities included asystole (one), atrial fibrillation (one), marked or moderate sinus arrhythmia (six), supraventricular tachycardia (one), atrial premature depolarizations (APDs; eight), ventricular premature depolarizations (VPDs; two), and bundle‐branch block (three). Mean seizure duration was longer in patients with abnormalities than in those without (204 vs. 71 s; p < 0.001). Generalized tonic–clonic seizures were also associated with increased occurrence of ictal ECG abnormalities (p = 0.006) as compared with complex partial seizures. There were no clinically significant differences in mean preictal and ictal/postictal PR and QTC intervals.

Conclusions: Cardiac rhythm and conduction abnormalities are common during seizures, particularly if they are prolonged or generalized, in intractable epilepsy. These abnormalities may contribute to SUDEP.
Focal Cortical–Subcortical Calcifications (FCSCs) and Epilepsy in the Indian Subcontinent
Authors: Singh Gagandeep , Sachdev M. S. , Tirath A. , Gupta A. K. , Avasthi G.
Published: August 2005

Summary: Purpose: A focal cortical–subcortical calcification (FCSC) is a common finding on computed tomography (CT) in individuals with focal or generalized seizures in the Indian subcontinent. We sought to determine the relation of FCSCs to epilepsy by comparing the lobe of seizure origin by electro‐clinical and CT evaluations and to study the nature and severity of epilepsy associated with FCSCs.

Methods: The relation of these FCSCs to epilepsy/seizures was studied in 40 patients, seen for the first time to the neurology outpatient department of a tertiary care hospital. An attempt was made to classify seizures and determine their lobe of origin based on clinical–electroencephalographic (EEG) criteria of the International League Against Epilepsy (ILAE). The clinical lobe of origin was compared with the location of the FCSC on CT scan. In addition, records of the CT unit of the same hospital were reviewed retrospecitvely, to identify cases with an FCSC and their referral diagnoses.

Results: Thirty‐one (77.5%) patients with FCSCs were considered to have localization‐related epilepsy (frontal lobe epilepsy, 20; temporal lobe epilepsy, three; parietal lobe epilepsy, one; occipital lobe epilepsy, three; and definitely localization related but having ambiguous localization features, four) based on ictal semiology and EEG studies. Other ILAE categories in the cohort included epilepsy without unequivocal focal or generalized features (four patients; 10%), isolated seizures (one patient; 2.5%), juvenile absence epilepsy (one patient; 2.5%), and insufficient data to classify epilepsy (three patients; 7.5%). Radiologic sites for FCSCs included frontal (20; 50%), temporal (six; 15%), parietal (seven; 17.5%), and occipital (seven; 17.5%). Electroclinical and radiologic data were congruent in localizing and lateralizing seizures in 22 (55%) patients. The FCSC was truly incidental in one patient with juvenile absence epilepsy. Discordance between the clinical and radiologic localizations was noted in five (12.5%) instances. Magnetic resonance imaging (MRI) did not reveal additional lesions corresponding to lobes of origin as determined by electroclinical analysis. Discordance was surmised to be a result of seizure spread from a silent region to symptomatic cortex. In 12 (30%) patients, electroclinical and radiologic congruence could not be ascertained because ictal descriptions were either inadequate or ambiguous, and EEG findings were noncontributory. Review of 4,452 CT scans of brain performed in the CT unit revealed 29 (0.65%) cases with FCSCs in individuals with nonseizure disorders, that could be labeled as incidental.

Conclusions: An FCSC is an important radiologic finding in localization‐related epilepsy in the Indian subcontinent. The severity of epilepsy ranges from asymptomatic cases to daily seizures.
An Assessment of Epilepsy Patients' Knowledge of Their Disorder
Authors: Long Lucretia , Reeves Andrew L. , Moore J. Layne , Roach Jessica , Pickering Carolyn T.
Published: August 2005

Summary: Purpose: Patient education is an effective component of comprehensive care. Studies assessing patient's knowledge of their epilepsy are scarce. We report the first objective study evaluating knowledge of epilepsy patients referred to an American tertiary care center.

Methods: Two hundred twenty epilepsy patients referred to an epilepsy center completed a knowledge questionnaire. The questionnaire included topics related to safety, compliance, and legal issues of driving and employment. Questionnaire scores were correlated with demographics, number of years with epilepsy, and educational background.

Results: Of 220 patients, 175 were included in study analysis. Thirteen percent (n = 28) were excluded because of the diagnosis of nonepileptic seizures, and 8% (n = 17) were excluded because of having a diagnosis other than epilepsy. The average age and number of years with epilepsy was 34.7 ± 13 and 14.4 ± 13.1, respectively. Neither age (r= 0.20, p 0.01), number of years with epilepsy (r= 0.09, p = 0.2), nor years of education (r= 0.34, p 0.01) correlated with questionnaire scores. Thirty percent believed that epilepsy is a mental disorder or contagious. Forty‐one percent believed it is appropriate to place an object in a patient's mouth during a seizure to prevent injury. Two of the lowest scores, 13.6% and 47.5%, pertained to the legal issues of driving and employment, respectively.

Conclusions: Patients with epilepsy are not knowledgeable about their disorder. This is true regardless of age, educational background, or number of years with epilepsy. There is a need for educational intervention in this population, particularly related to injury prevention and the legalities of driving and employment.
Social Aspects of Epilepsy in the Adult in Seven European Countries
Authors:   The RESt‐1 Group
Published: August 2005

Summary: Purpose: The social implications of epilepsy are ill‐defined, and there are no comparative findings from different countries. A multicenter cohort study has recently been completed on the risk of morbidity and accidents. The main social issues in the study population (patients with epilepsy and control subjects) are investigated and correlated to the clinical features of the disease.

Methods: Seven hundred six adult patients with idiopathic or remote symptomatic epilepsy and 662 matched controls without epilepsy were enrolled by secondary and tertiary centers in seven European countries (Italy, Germany, Spain, the Netherlands, England, Portugal, and Russia). At entry, patients and controls were interviewed, and data were collected on social variables (education, current occupation, marital status, driving, involvement in sports, and insurance). The main clinical features of epilepsy (seizure types, frequency and timing, disease duration, and syndrome) were also recorded.

Results: The sample included 690 men and 678 women aged 18 to 86 years. The level of education (mostly basic or high school) was slightly higher among patients with epilepsy. More patients than controls were single (56% versus 50%) or unemployed (18% versus 13%). Fewer patients than controls held a driver's license (44% versus 67%) or practiced sports (30% versus 41%). The distribution of each social variable varied significantly across countries, but with few exceptions, the differences between patients and controls were fairly similar. Based on multivariate analysis, for patients with epilepsy the odds ratio for driving was 0.27, and the corresponding odds ratios for sports involvement, better education, better occupation, and insurance were 0.59, 1.30, 0.60, and 1.49. Among patients with epilepsy, social variables were correlated to seizure remission and selected clinical features.

Conclusions: Comparative findings from different European countries support the concept that epilepsy has a considerable impact on driving and–to a lesser extent–on education, occupation, leisure activities, and insurance. The social implications of epilepsy in this sample are partly related to its severity and clinical features.
Effects of Vagus Nerve Stimulation on Progressive Myoclonus Epilepsy of Unverricht‐Lundborg Type
Authors: Smith Brien , Shatz Rhonna , Elisevich Kost , Bespalova Irina N. , Burmeister Margit
Published: August 2005

Summary: Purpose: A 34‐year‐old woman with progressive myoclonus epilepsy of Unverricht‐Lundborg type was considered for vagus nerve stimulation (VNS) therapy.

Methods: After demonstration of intractability to multiple antiepileptic regimens and progressive deterioration in cerebellar function, the patient was implanted with a vagus nerve stimulator and followed for 1 year. Neurological status, seizure frequency, and parameter changes were analyzed.

Results: VNS therapy resulted in reduction of seizures (more than 90%) and a significant improvement in cerebellar function demonstrated on neurological examination. The patient reported improved quality of life based in part on her ability to perform activities of daily living.

Conclusions: VNS therapy may be considered a treatment option for progressive myoclonus epilepsy. The effects of VNS on seizure control and cerebellar dysfunction may provide clues to the underlying mechanism(s) of action.
Claustral Lesions Delay Amygdaloid Kindling in the Rat
Authors: Mohapel Paul , Hannesson Darren K. , Armitage Lisa L. , Gillespie Greg W. , Corcoran Michael E.
Published: August 2005

Summary: Purpose: Lesions of the claustrum in cats and primates have been shown to disrupt the development and expression of amygdaloid‐kindled seizures in cats and primates. Because the structure and connectivity of the claustrum can vary between species, we wanted to examine the effects of claustral lesions on kindling in rats.

Methods: One group of rats received bilateral radiofrequency lesions of both anterior and posterior regions of the claustrum before amygdaloid kindling. Another group of rats received bilateral anterior and posterior radiofrequency lesions of the claustrum after amygdaloid kindling. Some rats were tested for transfer of kindling to the contralateral amygdala after claustral lesions.

Results: Small lesions that destroyed 13% of the claustrum were capable of delaying, but not blocking, amygdaloid kindling. The delay in kindling was due to an increase in the stimulation trials required to kindle to stage 5 seizures. The lesions had no effect on established kindled seizures or on transfer to the contralateral amygdala.

Conclusions: As in other species, the claustrum in the rat appears to play a role in kindling from the amygdala. Because of the restricted size of our claustral lesions, however, we were unable to conclusively assess the full extent of the claustrum's participation in limbic kindling.
Prospective Long‐Term Study of Vagus Nerve Stimulation for the Treatment of Refractory Seizures
Authors: DeGiorgio C. M. , Schachter S. C. , Handforth A. , Salinsky M. , Thompson J. , Uthman B. , Reed R. , Collin S. , Tecoma E. , Morris G. L. , Vaughn B. , Naritoku D. K. , Henry T. , Labar D. , Gilmartin R. , Labiner D. , Osorio I. , Ristanovic R. , Jones J. , Murphy J. , Ney G. , Wheless J. , Lewis P. , Heck C.
Published: August 2005

Summary: Purpose: To determine the long‐term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short‐term double‐blind trials have demonstrated its safety and efficacy, and one long‐term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long‐term study of VNS to date.

Methods: Patients with six or more complex partial or generalized tonic‐clonic seizures enrolled in the pivotal EOS study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active‐control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12‐month study.

Results: The median reduction at 12 months after completion of the initial double‐blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures.

Conclusions: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.
Pavor Nocturnus of Proven Epileptic Origin
Authors: Lombroso Cesare T.
Published: August 2005

Summary:Purpose: To evaluate the suspected epileptic origin in children with episodes masquerading as sleep terrors.

Method: One such child was investigated with scalp‐derived long‐term monitoring (LTM), inter and ictal single photon emission computed tomography (SPECT) scans, and an invasive LTM, followed by surgical subpial slicing of the focally discharging motor cortex.

Results: The scalp‐derived LTM and the SPECT scans did not localize the suspected epileptogenic focus. The invasive LTM revealed the focal onset of the ictal discharge. After the surgery, the seizures have been 90% controlled. No deficits resulted from the surgery.

Conclusions: Although most nocturnal terrors (NTs) are parasomnias, in a few children their frequent episodes that masquerade as NTs have an epileptic origin. There are several features to distinguish these from common NTs or from other frontal lobe epilepsies.
Dipole‐Source Analysis in a Realistic Head Model in Patients with Focal Epilepsy
Authors: Herrendorf G. , Steinhoff B. J. , Kolle R. , Baudewig J. , Waberski T. D. , Buchner H. , Paulus W.
Published: August 2005

Summary: Purpose: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located.

Methods: In five patients with mesial temporal epileptogenesis, confirmed by successful epilepsy surgery, the spike source was close to the hippocampus, with a mean distance of the dipole source from the hippocampus of 13.6 mm (range, 9–17.2 mm). In one case the ictal EEG also could be analyzed and resulted in a dipole‐source localization comparable to the interictal source.

Results: In both head models using either pure cortex segmentation only or a concentric three‐shell model, the dipole source was systematically dislocated in a more superior position. Data analysis by a second group with independently chosen EEG samples and identical individual head model resulted in deviations of >5.3 mm. Data analysis using independently selected spikes and independently segmented head models resulted in deviations 16.7 mm.

Conclusions: In four cases of extratemporal epileptogenesis, the origin of interictal epileptiform discharges was localized to the suspected primary epileptogenic zone.
Reliability and Validity of a Norwegian Version of the Quality of Life in Epilepsy Inventory (QOLIE‐89)
Authors: Stavem Knut , Bjørnes Helge , Lossius Morten I.
Published: August 2005

Summary: Purpose: To develop a Norwegian version of the Quality of Life in Epilepsy Inventory (QOLIE‐89) and to confirm its psychometric properties.

Methods: The QOLIE‐89 was adapted to Norwegian language through a translation‐backtranslation procedure. The assessment included 397 patients with epilepsy. We assessed internal consistency and test‐retest reliabilities. Construct validity was assessed by correlating scales with items of the 15D health status questionnaire, and discriminant validity was assessed by comparing scores for known groups.

Results: The internal consistency reliability (Cronbach's α, 0.76–0.92) and test‐retest reliability (intraclass correlation co‐efficient, 0.67–0.96) for the individual domains were acceptable. Spearman's rank correlations between QOLIE–89 domain scores and corresponding 15D single‐item scores were high (p, 0.47–0.76), and generally higher than the associations between noncorresponding items. Most QOLIE–89 items discriminated well between patients according to seizure status, psychiatric comorbidity, and working status; less well after antiepileptic drug use and neurologic comorbidity.

Conclusions: In this cross‐sectional survey, the Norwegian version of the QOLIE–89 was reliable and showed properties supporting construct validity, at a level comparable with the original U.S. version.
The Pathological Substrate of Limbic Epilepsy: Neuronal Loss in the Medial Dorsal Thalamic Nucleus as the Consistent Change
Authors: Bertram Edward H. , Scott Carol
Published: August 2005

Summary: Purpose: The focus of research in limbic epilepsy has been the hippocampus because of its well‐known pathology of hippocampal atrophy and sclerosis as well as the strong propensity for this structure to seize under a variety of circumstances. There is ample evidence, however, for pathological alterations in other regions of the limbic system in limbic/mesial temporal lobe epilepsy, including the amygdala, the entorhinal cortex, and, in some cases, the thalamus. In this preliminary evaluation of the pathological substrate for limbic epilepsy, we wished to determine if there was consistent anatomic change at extrahippocampal sites.

Methods: We compared paraffin sections of brains from rats with chronic spontaneous limbic epilepsy and age‐matched controls to determine the consistency of the pathology at five sites: the hippocampus, amygdala, entorhinal cortex, piriform cortex, and medial dorsal thalamus.

Results: In a qualitative evaluation of these sections taken from standardized positions, we found that the medial dorsal thalamic nucleus in the epileptic animals was the site that was consistently involved with neuronal loss. With all other sites, at least several animals had qualitatively normal tissue.

Conclusions: This finding suggests that neuronal loss in the medial dorsal thalamus may be the consistent pathology in limbic epilepsy, at least in an animal model of the disorder. The presence of a structurally abnormal subcortical region with broad connections to the limbic sites involved with chronic epilepsy may have implications for our understanding of the pathophysiology of this disorder.
Remodeling Dendritic Spines of Dentate Granule Cells in Temporal Lobe Epilepsy Patients and the Rat Pilocarpine Model
Authors: Isokawa Masako
Published: August 2005

Summary: Purpose: To study when dendritic alteration can occur in the epileptic hippocampus and how it is influenced by epileptic axonal reorganization.

Methods: Human specimens and the rat pilocarpine model were used. Dentate granule cells (DGCs) were visualized by intracellular biocytin injection for spine count.

Results: In the rat pilocarpine model, dendrites of DGCs revealed a generalized spine loss immediately after the acute status epilepticus induced by pilocarpine. However, this generalized damage was transient and was followed by recovery and plastic changes in spine shape and density, which occurred 15 to 35 days after the initial acute status, i.e., during the period of establishing a chronic phase of this model with the induction of spontaneous seizures. In human epileptic hippocampi, spine density was significantly higher when DGCs generated aberrant mossy fiber collaterals. This was particularly so in the proximal dendrite of DGCs, where the aberrant collaterals were densely localized. These findings suggest that initial acute seizures do not cause permanent damage in dendrites and spines of DGCs and that dendritic spines of epileptic neurons can respond to changes in the local cellular environment, including newly formed afferents, in a plastic manner.

Conclusion: Dendritic spines are dynamically maintained in chronic epilepsy during the course of establishment and maintenance of spontaneous seizures. Local dendritic spine alteration, detected later in the chronic phase of epilepsy, must have a separate cause from initial acute insults.
The Role of Mossy Cell Death and Activation of Protein Synthesis in the Sprouting of Dentate Mossy Fibers: Evidence from Calretinin and Neo‐Timm Staining in Pilocarpine‐Epileptic Mice
Authors: Silva Julieta G. , Mello Luiz E. A. M.
Published: August 2005

Summary: Mossy fiber sprouting is a major anatomical reorganization seen in patients with temporal lobe epilepsy and animal models of epilepsy. The final outcome of this reorganization is viewed by many as epileptogenic. Yet, important and relevant data from both human and animal models of epilepsy challenge this prevailing view. Regardless of the outcome of this debate, understanding of the mechanisms that underlie mossy fiber sprouting (MFS) might contribute to our understanding of both the adaptive and maladaptive changes that take place in the nervous system after injury. Available evidence suggests that two events might be crucial for mossy fibers to sprout in epilepsy: the death of mossy cells and the synthesis of trophic factors. The availability of means that prevent MFS, which is normally triggered after induction of status epilepticus, allow for the testing of hypotheses regarding the need for and the sufficiency of specific events for mossy fibers to sprout. We present data on a specific marker for mossy cells, calretinin, in the pilocarpine model of epilepsy in mice. Our data suggest that in the presence of a protein synthesis inhibitor status epilepticus—induced death of mossy cells is not sufficient to trigger mossy fiber sprouting. We suggest that both events, mossy cell death and synthesis of trophic factors, might be necessary for robust MFS to ensue.
Alterations of Glial Cell Function in Temporal Lobe Epilepsy
Authors: Heinemann U. , Gabriel S. , Jauch R. , Schulze K. , Kivi A. , Eilers A. , Kovacs R. , Lehmann T.‐N.
Published: August 2005

Summary: Purpose: Comparison of extracellular K+ regulation in sclerotic and nonsclerotic epileptic hippocampus.

Methods: Measurements of K+ signals with double‐barreled K+‐selective reference microelectrodes in area CA1 of slices from human and rat hippocampus, induction of increases in extracellular potassium concentration by repetitive alvear stimulation or iontophoresis, and block of inward‐rectifying and background K+ channels in astrocytes by barium.

Results: In the CA1 pyramidal layer from normal rat hippocampus, barium augmented extracellular K+ accumulation induced by iontophoresis or antidromic stimulation in a dose‐dependent manner. Similarly, barium augmented stimulusinduced K+ signals from nonsclerotic hippocampi (human mesial temporal lobe epilepsy). In contrast, barium failed to do so in sclerotic hippocampi (human mesial temporal lobe epilepsy, rat pilocarpine model).

Conclusions: Our findings suggest that in areas of reduced neuronal density (hippocampal sclerosis), glial cells adapt to permit rather large increases in extracellular potassium accumulation. Such increases might be involved in the transmission of activity through the sclerotic area.
Effects of Topiramate on Sodium‐Dependent Action‐Potential Firing by Mouse Spinal Cord Neurons in Cell Culture
Authors: McLean Michael J. , Bukhari Amjad A. , Wamil Artur W.
Published: August 2005

Purpose: The effects of topiramate (TPM) on sodium‐dependent action potentials were studied by using cultured mouse spinal cord neurons.

Methods: The ability of TPM to limit (block) depolarization‐induced spontaneous repetitive firing (SRF) was determined and compared with corresponding effects of phenytoin (PHT) and lamotrigine (LTG) in cultured mouse spinal neurons.

Results: Topiramate at concentrations of ges;3 μM caused a voltage‐sensitive and time‐dependent limitation of SRF that was associated with a decrease in the velocity of the upstroke of the action potential. At high concentrations (30–600 μM), TPM rapidly blocked SRF in about one third of the neurons tested and did not affect SRF in about one third. In some neurons, TPM caused an intermittent limitation (sputtering) of SRF (∼30% of the neurons) or blocked SRF only after a delay of several seconds (∼10%). This complex pattern of effects is distinctly different from that of PHT and LTG, in which the effect was always a rapid limitation or complete blockade of SRF. Another difference between TPM and the other anticonvulsants (AEDs) is that the effects of TPM were more dependent on the length of time the neurons were exposed to the compound and the intensity or duration of neuronal activity.

Conclusions: The results of this study do not support the concept that Na+ channel blockade is the primary mechanism responsible for the anticonvulsant activity of TPM.