bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colitis May Be Part of the Antiepileptic Drug Hypersensitivity Syndrome
Authors: Eland Ingo A. , Dofferhoff Anton S. M. , Vink Rob , Zondervan Pieter E. , Stricker Bruno H. Ch. 
Published: August 2005

Summary: Purpose: To show that colitis may be part of the antiepileptic hypersensitivity syndrome. Methods: Description of two case histories. Results: The first patient was a 47‐year‐old man who developed fever, lymphadenopathy, influenza‐like symptoms, facial edema, skin rash and diarrhea after 3 weeks of carbamazepine (CBZ) treatment. Laparotomy because of severe abdominal pain 2 weeks later showed severe colitis with perforations. The second patient was a 41‐year‐old woman who developed fever, diarrhea, and skin rash 4 weeks after start of CBZ treatment. A colon biopsy confirmed colitis. Stool examinations did not show pathogenic microorganisms, and there was no evidence of Crohn's disease or ulcerative colitis. Both patients had elevated liver enzymes, peripheral eosinophilia, and eosinophils in the infiltrate of the colon. Conclusions: In view of the close temporal relation between start of CBZ intake and development of colitis, the presence of fever, lymphadenopathy, and rash, and improvement after discontinuation of CBZ, we conclude that the two patients developed an AED hypersensitivity syndrome. Our case histories demonstrate that severe colitis may be part of this syndrome.
No Evidence of a Major Locus for Benign Familial Infantile Convulsions on Chromosome 19q12‐q13.1
Authors: Gennaro Elena , Malacarne Michela , Carbone Ilaria , Riggio Maria Concetta , Bianchi Amedeo , Bonanni Paolo , Boniver Clementina , Bernardina Bernardo Dalla , De Marco Pasquale , Giordano Lucio , Guerrini Renzo , Santorum Enrica , Sebastianelli Rosella , Vecchi Marilena , Veggiotti Pierangelo , Vigevano Federico , Bricarelli Franca Dagna , Zara Federico 
Published: August 2005

Summary: Purpose: A locus for benign familial convulsions (BFICs) has been recently mapped on chromosome 19q12–13.1 by studying five families of Italian descent. The main goal of this study was to investigate the role of this locus in a set of seven newly identified families with at least three affected cases. Methods: Five polymorphic microsatellite markers covering the BFIC locus on chromosome 19q have been typed, and parametric linkage analysis has been performed to analyze the segregation of the BFIC locus within our families. Results: Cumulative 2‐point lod scores and multipoint analysis showed no evidence of linkage between chromosome 19 markers and the BFIC phenotype. The analysis of family‐specific 2‐point lod scores and haplotypes, however, indicated the presence of linkage to chromosome 19q in a single family, suggesting genetic heterogeneity within our family sample. Conclusions: Our study demonstrates that the previously reported BFIC locus on chromosome 19q12–13.1 is not a major locus for BFICs. We suggest that genetic heterogeneity may have generated our discordant linkage findings, as it was reported in benign familial neonatal convulsions, a related idiopathic mendelian syndrome.
The Neuropathology of Hyperthermic Seizures in the Rat
Authors: Jiang W. , Duong T. M. , Lanerolle N. C. de 
Published: August 2005

Summary: Purpose: Single and repeated hyperthermic seizures were induced in rats beginning at age 22 days to determine the neuroanatomic consequences to the hippocampus and to compare these changes with those in the hippocampi of patients with temporal lobe epilepsy (TLE) experiencing febrile seizures. Methods: Hyperthermic seizures were induced by placing rats in a bath of water at 45°C for 4 min. Seizures were visually observed, and some animals also were monitored electroen‐cephalographically. Neurodegeneration was examined with a silver stain, whereas granule cell sprouting was detected with the Timm stain. Results: In a majority of rats, hyperthermia‐induced tonicclonic seizures ranged in duration from 30 s to 6 min; the seizure duration increased with the number of seizures. No neurodegeneration was detectable in these animals, although there was sprouting of granule cell collaterals into the inner molecular layer (IML) of the dentate. In a small number of animals, the short seizures evolved into status epilepticus, and neuronal degeneration was present in the hippocampus and other parts of the temporal lobe, and the mediodorsal thalamus. Conclusions: This study confirms the relation between hyperthermia and seizure occurrence. It shows in particular that, as in the human, only prolonged seizures such as status epilepticus cause a pattern of neurodegeneration similar to that observed in human TLE.
Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis
Authors: Pennell P. B. , Burdette D. E. , Ross D. A. , Henry T. R. , Albin R. L. , Sackellares J. C. , Frey K. A. 
Published: August 2005

Summary: Purpose: Prior single‐photon emission tomography studies showed losses of muscarinic acetylcholine receptor (MAChR) binding in patients with refractory mesial temporal lobe epilepsy. Experimental animal studies demonstrated transient losses of MAChR due to electrically induced seizures originating in the amygdala. However, the relations between cholinergic synaptic markers, seizures, and underlying neuro‐pathology in human temporal lobe epilepsy are unknow. We tested the hypotheses that human brain MAChR changes are attributable to hippocampal sclerosis (HS), and that HS resembles axon‐sparing lesions in experimental animal models. Methods: We measured MAChR binding‐site density, an intrinsic neuronal marker, within the hippocampal formation (HF) in anterior temporal lobectomy specimens from 10 patients with HS and in 10 autopsy controls. Binding‐site density of the presynaptic vesicular acetylcholine transporter (VAChT) was measured as a marker of extrinsic cholinergic afferent integrity. MAChR and VAChT results were compared with neuronal cell counts to assess their relations to local neuronal losses. Results: Reduced MAChR binding‐site density was demonstrated throughout the HF in the epilepsy specimens compared with autopsy controls and correlated in severity with reductions in cell counts in several HF regions. In contrast to MAChR, VAChT binding‐site density was unchanged in the epilepsy specimens compared with autopsy controls. Conclusions: Reduction in MAChR binding in HS is attributable to intrinsic neuronal losses. Sparing of afferent septal cholinergic terminals is consistent with the hypothesis that an excitotoxic mechanism may contribute to the development of HS and refractory partial epilepsy in humans.
The Effect of Menopause and Perimenopause on the Course of Epilepsy
Authors: Harden Cynthia L. , Pulver Melissa C. , Ravdin Lisa , Jacobs Alan R. 
Published: August 2005

Summary: Purpose: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone‐replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course. Methods: We performed a questionnaire study of women with epilepsy currently in menopause and perimenopause, requesting information regarding the course of their epilepsy and treatment. Statistical analysis was performed by using Pearson X2 with 95% confidence limits. Results: Forty‐two menopausal women (ages 41–86 years) responded. Twelve subjects reported no change in seizures at menopause, 17 reported a decrease in seizure frequency, and 13 reported an increase. Sixteen (38%) took synthetic HRT. Sixteen (38%) additional subjects (having some overlap with the HRT group) reported having a catamenial seizure pattern before menopause. HRT was significantly associated with an increase in seizures during perimenopause (p = 0.001). A history of catamenial seizure pattern was significantly associated with a decrease in seizures at menopause (p = 0.013). Thirty‐nine perimenopausal women (ages 38–55 years) responded. Nine subjects reported no change in seizures at perimenopause, five reported a decrease in seizure frequency, and 25 reported an increase. Eight (15%) subjects took synthetic HRT, and 28 (72%) reported having a catamenial seizure pattern before menopause. HRT had no significant effect on seizures; however, a history of catamenial seizure pattern was significantly associated with an increase in seizures at perimenopause (p = 0.02). Conclusions: These pilot data suggest that synthetic HRT may be associated with an increase in seizure frequency in menopausal women with epilepsy. A catamenial seizure pattern may be associated with seizure decrease during menopause but with an increase during perimenopause.
The Long‐Term Use of Gabapentin, Lamotrigine, and Vigabatrin in Patients with Chronic Epilepsy
Authors: Wong I. C. K. , Chadwick D. W. , Fenwick P. B. C. , Mawer G. E. , Sander J. W. A. S. 
Published: August 2005

Summary:Purpose:To compare the long‐term retention of gabapentin (GBP), lamotrigine (LTG), and vigabatrin (VGB) by patients with chronic epilepsy and the reasons for treatment discontinuation. To assess the likelihood of seizure freedom, seizure‐related injury/hospital admission and mortality after these drugs were commenced.Methods:This was a retrospective case‐records survey in five tertiary referral epilepsy centres in the U.K. The retention times on treatment (from initiation to discontinuation) for the different antiepileptic drugs (AEDs) were compared by using Kaplan‐Meier survival analysis and Cox regression. Incidences of seizure freedom and seizure‐related injury/hospital admissions and standardised mortality ratios were calculated.Results:There were 1,375 patients with chronic epilepsy included; 361 were taking GBP, 1,050 LTG, and 713 VGB. The retention of GBP, LTG, or VGB was >40% at 6 years. Fewer than 4% of patients become seizure free while taking one of the drugs. There was no reduction in mortality or seizure‐related injury/admission.Conclusions:The impact of these new AEDs on chronic epilepsy can be described only as modest. This view may be revised, however, as more experience is gained with new drugs in previously untreated patients.
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.