bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Negative Mood States Associated with Cognitive Function in Newly Diagnosed Patients with Epilepsy?
Authors: Pulliainen Veijo , Kuikka Pekka , Kalska Hely
Published: August 2005

Summary: Purpose: The association of self‐reported subclinical depressive symptoms and negative mood states with cognitive functioning was evaluated in 51 consecutive newly diagnosed adult persons with epilepsy.

Methods: Emotional state was assessed with Profile of Mood States (POMS) and Brief Depression Scale (BDS) and was correlated with a battery of neuropsychological tests.

Results: Patients with epilepsy reported more depressive symptoms in BDS than in controls. They also had more feeling of bewilderment and less vigor on POMS. Higher scores in BDS and in POMS inefficiency scale were associated with slower nondominant hand tapping, but emotional state did not correlate with cognitive measures within the epilepsy group.

Conclusions: Self‐reported symptoms of depression and negative mood states were not extensively or significantly associated with cognitive function, and they do not explain the cognitive impairments observed in cognition in newly diagnosed patients with epilepsy.
Burns in Patients with Epilepsy: Changes in Epidemiology and Implications for Burn Treatment and Prevention
Authors: Josty I. C. , Narayanan V. , Dickson W. A.
Published: August 2005

Summary: Purpose: To determine the epidemiology of burns in patients with epilepsy and to identify changes in epidemiology compared with previous studies; to identify further strategies that can be used in the primary and secondary prevention of such injuries in this group of patients.

Methods: A retrospective case note review of 111 patient episodes to a regional burns unit where the admission criterion was a burn secondary to an epileptic seizure.

Results: The majority (60 of 111) of burns were due to scald injury and were sustained in a domestic setting. This group of patients (mean age, 42.7 years) accounted for 1.6% of admissions during the study period. The data demonstrate a change in the epidemiology when compared with previous studies. Most burns were small (mean area burnt, 2.2%) but deep, and 72 of 111 patient episodes required surgery, and 12% of patients had reburn injuries requiring readmission.

Conclusions: Scald injuries are now the major cause of burns in those with epilepsy, and the proportion of such patients admitted to a regional burns unit has reduced. Patients and health professionals need to be aware of such injuries and of appropriate prevention strategies.
Ictal SPECT and Interictal PET in the Localization of Occipital Lobe Epilepsy
Authors: Sturm Jonathan W. , Newton Mark R. , Chinvarun Yotin , Berlangieri Salvatore U. , Berkovic Samuel F.
Published: August 2005

Summary: Purpose: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose–positron emission tomography (FDG‐PET) in refractory occipital lobe epilepsy.

Methods: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy.

Results: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies.

Conclusions: Ictal SPECT can provide novel localizing data in MRI‐negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.
Cluster Analysis of Clinical Seizure Semiology of Psychogenic Nonepileptic Seizures
Authors: Gröppel G. , Kapitany T. , Baumgartner C.
Published: August 2005

Summary: Purpose: To develop an objective classification of psychogenic nonepileptic seizures (NES) based on cluster analysis of clinical seizure semiology.

Methods: We studied the clinical seizure semiology in 27 patients with psychogenic NES documented by prolonged video‐EEC monitoring. We analyzed the following clinical symptoms: clonic and hypermotor movements as well as trembling of the upper and/or lower extremities, pelvic thrusting, head movements, tonic posturing backward of the head, and falling. We used cluster analysis to identify symptoms occurring together in a systematic way and thus tried to achieve a clinical classification of psychogenic NES.

Results: We could identify three symptom clusters. Cluster 1 was characterized by clonic and hypermotor movements of the extremities, pelvic thrusting, head movements, and tonic posturing of the head, and therefore was named “psychogenic motor seizures.” Cluster 2 comprised trembling of the upper and lower extremities and was termed “psychogenic minor motor or trembling seizures.” Cluster 3 consisted of falling to the floor as the only symptom and was referred to as “psychogenic atonic seizures.”

Conclusions: Our study represents the first study to analyze the clinical semiology of psychogenic NES by cluster analysis, which should be useful for an objective classification of psychogenic NES. This classification should allow both a better characterization of psychogenic NES and an easier differential diagnosis against specific epileptic seizures.
Methsuximide Lowers Lamotrigine Blood Levels: A Pharmacokinetic Antiepileptic Drug Interaction
Authors: Besag F. M. C. , Berry D. J. , Pool F.
Published: August 2005

Summary: Purpose: To determine whether methsuximide (MSM) affects lamotrigine (LTG) blood levels and whether any change is of clinical significance.

Methods: LTG serum levels in 16 patients taking MSM were compared with those before starting or after stopping the MSM. The 16 patients, (11 boys, five girls) were young people (mean age, 15.5 years; range, 9–19 years) with a variety of seizure types and syndromes. In six cases, LTG levels were available both before MSM was started and after it was stopped.

Results: The mean LTG serum concentration before starting or after stopping MSM was 13.4 mg/L, and the mean level while taking MSM was 6.3 mg/L. This difference was highly significant (p < 0.0005, paired t test). MSM lowered the LTG serum concentration in every case, with a mean decrease of 53% (range, 36–72%). In some patients this led to a deterioration in seizure control when MSM was added or an improvement in seizure control after MSM was stopped.

Conclusions: Although MSM is a valuable add‐on, broad‐spectrum drug when used in combination with LTG, adjustment of the LTG dose may be necessary when MSM is started or stopped, to allow for the fact that MSM lowers LTG blood levels.
Health‐Related Quality of Life Outcome in Medically Refractory Epilepsy Treated with Anterior Temporal Lobectomy
Authors: Markand Omkar N. , Salanova Vicenta , Whelihan Eileen , Emsley Christine L.
Published: August 2005

Summary: Purpose: A prospective study to investigate health‐related quality of life (HRQOL) outcome in patients with temporal lobe epilepsy treated with anterior temporal lobectomy (ATL).

Methods: The majority of the patients with medically refractory focal epilepsy had Quality of Life in Epilepsy‐89 (QOLIE‐89) assessment at the time of prolonged video/EEG monitoring as part of their presurgical evaluation. Thirty‐seven patients who were not treated surgically constituted the control group, and 53 patients who underwent ATL made up the surgery group. Both control and surgery groups had HRQOL assessment repeated at ∼1‐ and 2‐year intervals. Repeated measures analysis of variance (ANOVA) was used to test for differences between the two groups.

Results: For the overall score and almost every scale, the surgery group had a higher baseline mean than the control group. Because of this baseline difference, change scores were used in further analysis. The overall score and 10 of 17 scales in QOLIE‐89 showed significant HRQOL improvement after ATL, and the improvement was significant relative to score changes of the nonsurgical comparison group. Scores improved in overall QOL, emotional well‐being, attention/concentration, language, social isolation, health perception, role limitations‐physical, work/drive/social, health discouragement, and seizure worry. For the first five scales, there was group‐time interaction; the improvement was significantly more on the 2‐year than on the 1‐year follow‐up. When the surgery patients were divided into four categories (class IA‐, completely seizure free; class IA+, seizure free with aura; class II, rare seizures; class III, worthwhile improvement in seizure control; and class IV, no improvement), the improved HRQOL in the surgery group was almost entirely contributed by the class IA‐ outcome patients who were totally seizure free. The class IA+ patients with continuing aurae and class II/III/IV patients had no significant improvement in their overall HRQOL scores at 1‐ or 2‐year follow‐up.

Conclusions: Overall score and 10 of the 17 scales of QOLIE‐89 significantly improved in patients with medically refractory temporal lobe epilepsy after ATL. For some scales, there was delay in the improvement to manifest. The HRQOL improvement was related to achieving an entirely seizure‐free status (i.e., no seizures or aurae postoperatively).
Prevalence, Classification, and Severity of Epilepsy in Children in Western Norway
Authors: Waaler P. E. , Blom B. H. , Skeidsvoll H. , Mykletum A.
Published: August 2005

Summary: Purpose: To determine prevalence of active epilepsy in school children in a defined area and assess the usefulness of International League Against Epilepsy classification of seizures and epileptic syndromes, with special emphasis on frequency, additional handicaps, and therapeutic problems of severe cases.

Methods: The latest International League Against Epilepsy International Classification of Epileptic Seizures (ICES, 1981) and Epilepsies and Epileptic Syndromes (ICE, 1989) were used for determination of prevalence rates, seizure types, epilepsies and epileptic syndromes, and additional neurological deficits in all 6‐ to 12‐year‐old children with epilepsy in a Norwegian county. Children had neuropediatric and EEG examination, intelligence evaluation, and, when necessary, additional investigations.

Results: Prevalence of active epilepsy on January 1, 1995, was 5.1 per 1,000. Main seizure type and epilepsy syndrome could be classified in 98% and 90% of patients, respectively. Seizure types/epileptic syndromes were more often partial/localization related than generalized. Among generalized epilepsies, idiopathic forms were more frequent in girls, and cryp‐togenic and symptomatic forms more frequent in boys. Epileptogenic EEG activity was most often generalized or localized to one or two areas of the brain and was never found in 14% of patients. Symptomatic etiology was found in 46% of all children and in 81% of therapy‐resistant cases, respectively. Over the years, 11% of children had never used antiepileptic drugs (AED), 62% had tried one or two AEDs, and 26% had tried from three to 15 AEDs. Twenty‐five percent of children were without present AED treatment. Complementary/alternative medicine had been tried by 12% of children.

Conclusions: Although most epilepsies could be classified, the number of cases in non‐specific categories was relatively high. Symptomatic etiology was frequent, especially in therapy‐resistant cases. Multidisciplinary therapeutic and ha‐bilitation approaches are often needed in childhood epilepsy.
Conduct of Trials in Private Clinical Practice
Authors: Beran Roy G. , Beran Maureen E.
Published: August 2005

Summary: Purpose: Trials of antiepileptic medications are usually based in tertiary referral centers with teaching hospital resources. Epilepsy Research & Services (ERS) is part of a private outpatient neurological clinic that is involved in research as part of multicenter clinical trials, adhering to Good Clinical Research Practice. ERS is subject to external monitoring and auditing, but does so outside of the teaching hospital environment.

Methods: The clinic is operated by a neurologist supported by a research assistant, administrative and nursing staff and has no formal university attachment. Patients are recruited for trials from routine referrals for clinical care. The center has formal ties with the ethics committee of the local teaching hospital, but none of the team is formally attached to that hospital.

Results: The center conducted trials of zonisamide, oxcar‐bazepine, gabapentin, remacemide, tiagabine, vigabatrin, felbamate, and lamotrigine both as add‐on trials in refractory seizure disorders and as monotherapy trials in de novo epilepsy. More than 200 patients have been recruited for trials at ERS (with some patients being involved in more than one trial). External review endorsed ERS as a superior environment for such research and as a model for other centers.

Conclusions: Private practice is a viable alternative for the conduct of clincial trials and should be considered when establishing such protocols. Simplicity of administration and clinical practice, which more closely mirrors standard patient care, may enhance recruitment and management.
Successful Use of Intravenous Immunoglobulin as Initial Monotherapy in Landau‐Kleffner Syndrome
Authors: Mikati Mohamad A. , Saab Raya
Published: August 2005

Summary: Purpose: There is a need for new and more effective therapies for Landau‐Kleffner syndrome. In this article we present the first case in which a patient with Landau‐Kleffner syndrome was given intravenous immunoglobulin (IVIG) as his first and only therapy and responded to it.

Methods: This previously healthy, left‐handed boy presented at 31 months of age with a 3‐month history of auditory agnosia, behavioral abnormalities, and progressive, eventually complete loss of speech. Electroencephalography (EEG) showed frequent and, in sleep, continuous right central and temporal spike slow wave discharges. Metabolic workup, magnetic resonance imaging, and auditory evoked potentials were normal. Cere‐brospinal fluid IgG index was high (18%). The patient was treated with IVIG, as his initial and only therapy, receiving 500 mg/kg/day over four consecutive days.

Results: On the third day of IVIG, the patient started using single words, and on the fourth, two‐word sentences. Two weeks later his speech and behavior returned to normal. At the end of 4 days of IVIG therapy, EEG was within normal limits. Two months later, however, he had a severe relapse clinically and by EEG. He promptly responded to another course of IVIG. A subsequent cerebrospinal fluid IgG index showed normalization (6%). Three months later he had essentially normal speech and behavior.

Conclusions: Repeated, immediate, and remarkable clinical and EEG responses of this patient suggest that IVIG was helpful as first‐line therapy in the treatment of Landau‐Kleffner syndrome. It also supports the hypothesis that immunological mechanisms contributed to his symptoms.
Chromosomal Mapping of Genes for Epilepsy in NER: A Rat Strain with Tonic‐Clonic Seizures
Authors: Maihara Toshiro , Noda Atsushi , Yamazoe Hiroshi , Voigt Birger , Kitada Kazuhiro , Serikawa Tadao
Published: August 2005

Summary: Purpose: NER is a mutant rat strain that exhibits spontaneous tonic‐clonic convulsions accompanied by epileptic discharges on ictal EEG and serves as a model for generalized tonic‐clonic seizures in humans. Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic‐clonic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map.

Methods: We developed F1 hybrid (F1) and reciprocal back‐cross progenics of NER with a seizure‐resistant strain, F344, and evaluated their seizure susceptibility under tossing‐stimulated and nonstimulated conditions. Backcross animals were genotyped using simple sequence length polymorphism markers for polymerase chain reactions. Linkage between seizure susceptibility and marker loci was analyzed by χ2 statistic tests and by the computer programs MAPMAKER/EXP and MAPMAKER/QTL.

Results: Under tossing‐stimulating conditions, tonic‐clonic seizures were provoked in 90% of NER and 66% of (F1 × NER) backcross animals, but no seizures occurred in the F344, F1, or (F1 × F344) backcross animals. Routine monitoring of nonstimulated animals revealed spontaneous tonic‐clonic convulsions in 100% of NER and 64.2% of (F1 × NER) backcross animals, but no seizures in F344 or F1. Gender effect on seizure susceptibility was negligible in (F1 × NER) backcross in both conditions. Preliminary genome‐wide scanning and subsequent precise location of the causative genes revealed seizure susceptibility loci, designated Nerl and Ner2, on rat chromosomes 1 and 3, respectively.

Conclusions: Nerl is a locus that controls the inheritance of spontaneous tonic‐clonic seizures in an autosomal recessive mode, whereas Ner2 affects the occurrence of tossing‐induced seizures. Orthologous genes in the vicinity of these loci may be related to epileptogenesis in other species, including humans.
The Role of Brain Computed Tomography in Evaluating Children with New Onset of Seizures in the Emergency Department
Authors: Maytal Joseph , Krauss Joel M. , Novak Gerald , Nagelberg Joy , Patel Mahindra
Published: August 2005

Summary: Background: The purpose of neuroimaging of a patient with new onset of seizures is to demonstrate cause and explore the prognosis. It was recently recommended that emergency brain computed tomography (CT) be performed only in adult seizure patients with an increased likelihood of life‐threatening lesions, i.e., those with new focal deficits, persistent altered mental status, fever, recent trauma, persistent headaches, history of cancer, history of anticoagulation, or suspicion of acquired immunodeficiency syndrome. The objective of this study was to determine the diagnostic utility of emergency brain CT in children who present to the emergency department with new onset of seizures.

Methods: A 1‐year retrospective chart review of all children who presented to the emergency department of the Schneider Children's Hospital with a new onset of seizures and who underwent CT of the brain, excluding children with simple febrile seizures.

Results: Sixty‐six patients, 34 boys and 32 girls with a mean age of 4.9 years, qualified for inclusion in the study. Fifty‐two patients (78.8%) had normal CT results and 14 patients (21.2%) had abnormal CT results. Seizure cause was considered cryptogenic in 33 patients, of whom 2 (6%) had abnormal CT results; neither patient required intervention. Seizure cause was considered symptomatic in 20 patients, of whom 12 (60%) had abnormal CT results (p < 0.0001). In two patients with abnormal CT scans (both acute symptomatic), the imaging findings were of immediate therapeutic significance and were predictable from the clinical history and the physcial examination. None of the 13 patients with complex febrile seizure cause had an abnormal CT scan. Patients with partial convulsive seizures were more likely to have abnormal CT scans than patients with generalized convulsive seizures, but the difference was not statistically significant.

Conclusions: The routine practice in many pediatric emergency Department of obtaining brain CT scans for all patients with new onset of nonfebrile seizures is unjustified. History and physical examination are sufficient to identify those patients for whom such studies are likely to be appropriate. Emergent CT is not indicated for patients with no known seizure risk factors, normal neurological examinations, no acute symptomatic cause other than fever, and reliable neurological follow‐up. For these patients, referral to a pediatric neurologist for further workup, including electroencephalography and the more diagnostically valuable magnetic resonance imaging, would be more appropriate.
Comparative Stereoselective Pharmacokinetic Analysis of 10‐Hydroxycarbazepine After Oral Administration of its Individual Enantiomers and the Racemic Mixture to Dogs
Authors: Volosov Andrew , Yagen Boris , Bialer Meir
Published: August 2005

Summary: Purpose: 10‐hydroxycarbazepine (MHD) is the active metabolite of the new antiepileptic drug oxcarbazepine. MHD is a chiral molecule with an asymmetric carbon at position 10. The purpose of this study was to evaluate the stereoselectivity in the pharmacokinetics of the enantiomers of MHD after oral administration of the individual MHD enantiomers and the racemic mixture to dogs.

Methods: A racemic mixture of MHD and the individual MHD enantiomers were administered to six dogs in a crossover design. Plasma and urine concentrations of R(−)‐ and S(+)‐MHD were determined by a stereoselective high‐performance liquid chromatography assay.

Results: The area under the concentration‐time curve of R(−)‐MHD was significantly greater than that of S(+)‐MHD after the administration of the individual enantiomers but not after the administration of MHD in a racemic form. The formation clearance of the S(+)‐MHD glucuronide was approximately three times greater than that of R(−)‐MHD glucuronide. No difference was found in the renal clearance and protein binding of R(−)‐ and S(+)‐MHD enantiomers.

Conclusions: The pharmacokinetics of the MHD enantiomers was found to be stereoselective, mainly as a result of the stereoselectivity in the glucuronidation process. The difference in the pharmacokinetic parameters found after administration of individual MHD enantiomers compared with the administration of MHD in a racemic form suggests the possibility of interaction between the two enantiomers. Stereoselective pharmacokinetic and pharmacodynamic studies are needed to evaluate the rationale of developing MHD as a new antiepileptic drug, either in a stereospecific or racemic form.
Interictal Cardiovascular Autonomic Responses in Patients with Temporal Lobe Epilepsy
Authors: Ansakorpi Hanna , Korpelainen Juha T. , Suominen Kalervo , Tolonen Uolevi , Myllylä Vilho V. , Isojärvi Jouko I. T.
Published: August 2005

Summary:Purpose: To measure interictal cardiovascular autonomic functions in patients with either refractory or well‐controlled temporal lobe epilepsy (TLE).

Methods: For autonomic assessment, heart rate variation during normal and deep breathing, Valsalva maneuver, and tilting were measured in 19 patients with chronic refractory TLE, 19 patients with well‐controlled TLE, and 38 age‐ and sex‐matched healthy control subjects. Blood pressure responses to tilting and isometric work also were evaluated.

Results: Heart‐rate (HR) variation during normal breathing (p = 0.006) and tilting (p = 0.043) was lower in patients with refractory TLE than in control subjects. Heart‐rate response to tilting (p = 0.036) was also lower in patients with well‐controlled TLE than in control subjects. Blood‐pressure responses showed no differences between the patients and the control subjects. Patients taking carbamazepine (CBZ) medication had decreased HR responses to deep breathing (p = 0.046) and to tilting (p = 0.014) compared with the control subjects.

Conclusions: Refractory TLE seems to be associated with dysfunction of the cardiovascular autonomic regulation, manifesting as impaired HR responses to certain stimuli. Interictal autonomic dysfunction is seen in patients with well‐controlled TLE as well, but it may be more evident in patients with refractory epilepsy. CBZ medication may also be associated with altered autonomic cardiac control.
Treatment of Refractory Complex‐Partial Status Epilepticus with Propofol: Case Report
Authors: Begemann Martin , Rowan A. James , Tuhrim Stanley
Published: August 2005

Summary: Purpose: We report a case of a 65‐year‐old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneu‐rysm and developed nonconvulsive status epilepticus of the complex‐partial type, refractory to phenytoin (PHT), phenobar‐bital (PB), valproate (VPA), and lorazepam (LZP).

Methods: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG).

Results: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery.

Conclusions: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.
Magnetoencephalography in Focal Epilepsy
Authors: Baumgartner Christoph , Pataraia Ekaterina , Lindinger Gerald , Deecke Lüder
Published: August 2005

Summary: The introduction of whole‐head magnetoencephalographic (MEG) systems facilitating simultaneous recording from the entire brain surface has led to a major breakthrough in the MEG evaluation of epilepsy patients. MEG localizations estimates of the interictal spike zone showed excellent agreement with invasive electrical recordings and were useful to clarify the spatial relationship of the irritative zone and structural lesions. MEG appears to be especially useful for study of patients with neocortical epilepsy, and helped to guide the placement of subdural grid electrodes in patients with nonlesional epilepsies. MEG could differentiate between patients with mesial and lateral temporal seizure onset. Spike propagation in the temporal lobe and the spatio–temporal organization of the interictal spike complex could be studied noninvasively. MEG was useful to delineate essential brain regions before surgical procedures adjacent to the central fissure. MEG appears to be more sensitive than scalp EEG for detection of epileptic discharges arising from the lateral neocortex, whereas only highly synchronized discharges arising from mesial temporal structures could be recorded. A major limitation of MEG has been the recording of seizures because long‐term recordings cannot be performed on a routine basis with the available technology. Because MEG and EEG yield both complementary and confirmatory information, combined MEG–EEG recordings in conjunction with advanced source modeling techniques should improve the noninvasive evaluation of epilepsy patients and further reduce the need for invasive procedures.
Chromogranins in Temporal Lobe Epilepsy
Authors: Kandlhofer Susanne , Hoertnagl Brigitte , Czech Thomas , Baumgartner Christoph , Maier Hans , Novak Klaus , Sperk Günther
Published: August 2005

Summary: Purpose: Chromogranins are neuropeptide precursors stored in large dense core vesicles. Because physiological functions have been postulated for peptides originating from chromogranins, we investigated the distribution of chromogranins A and B and secretoneurin (a peptide derived from secretogranin II) in the control and epileptic hippocampus of humans and rats.

Methods: Chromogranin immunoreactivity (IR) was investigated in paraformaldehyde‐fixed hippocampal specimens from 24 temporal lobe epilepsy patients with intractable seizures, postmortem from 15 patients deceased from nonneurological disorders, in rats 30 days after kainate‐induced limbic seizures, and in control rats.

Results: In control rats and in humans, chromogranin A and B IR and secretoneurin IR were present in mossy fibers. In addition, chromogranin B IR was found in granule cells, and chromogranin A IR was found in granule and CA2 pyramidal cells in the human hippocampus. In both species, chromogranin B and secretoneurin were unevenly distributed in the molecular layer of the dentate gyrus. The most intriguing change seen in human temporal lobe epilepsy specimens and in the kainic acid model of the rat was the prominent staining of the inner molecular layer, indicating storage of chromogranins A and B and secretoneurin in terminals of reorganized mossy fibers, from which they may be released upon nerve stimulation.

Conclusion: Chromogranins A and B and secretoneurin are valid markers for hippocampal neurons and delineate epilepsy‐induced reorganization of mossy fibers.
Topiramate as an Inhibitor of Carbonic Anhydrase Isoenzymes
Authors: Dodgson Susanna J. , Shank Richard P. , Maryanoff Bruce E.
Published: August 2005

Purpose: This study investigated the effectiveness of topiramate (TPM) as an inhibitor of six isozymes of carbonic anhydrase (CA).

Methods: The inhibition constants (Ki) of TPM and acetazolamide (AZM) for CA I, CA II, CA III, CA IV, CA V, and CA VI were determined for human (HCA), rat (RCA), or mouse (MCA). The activity of CA was studied by using purified isozymes, erythrocytes, subcellular fractions of kidney or brain, and saliva, and was assayed at 37°C or 25°C by 18O mass spectrometry and/or by measuring the pH shift at 0°C.

Results: Topiramate Ki values for HCA I, HCA II, HCA IV, and HCA VI were ∼100, 7, 10, and >100 μM, respectively. TPM Ki values for RCA I, RCA II, RCA III, RCA IV, and RCA V were ∼180, 0·1 to 1, >100, 0·2 to 10 and 18 μM, respectively. For RCA II and RCA IV, the Ki values were temperature dependent. TPM Ki values for MCA II and MCA IV ranged between 1 and 20 μM.

Conclusions: These results indicate that TPM is more potent as an inhibitor of CA II and CA IV than of CA I, CA III, and CA VI. In all three species, AZM was usually 10 to 100 times more potent than TPM as an inhibitor of CA isozymes.
Effects of Topiramate on Sustained Repetitive Firing and Spontaneous Recurrent Seizure Discharges in Cultured Hippocampal Neurons
Authors: DeLorenzo Robert J. , Sombati Sompong , Coulter Douglas A.
Published: August 2005

Purpose: In this study, we examined the effects of topiramate (TPM) on the electrophysiologic properties of cultured rat hippocampal pyramidal neurons.

Methods: Whole‐cell current‐clamp recording techniques were used to determine the effects of TPM on sustained repetitive firing (SRF), spontaneous epileptiform‐burst firing, and spontaneous recurrent seizures (SRS).

Results: Topiramate at therapeutic concentrations (10–100 μM) significantly decreased or abolished SRF in a dose‐dependent and partially reversible manner. When transiently exposed to a medium in which Mg2+ is omitted, hippocampal neurons in culture develop SRS (“epilepsy”) and epileptiform discharges. Application of TPM at concentrations ranging from 10 to 100 μM to cells displaying seizure activity caused a concentration‐dependent decrease in the number of action potentials within a burst and in the average duration of epileptiform activity. Both effects were partially reversed during a 5‐ to 30‐min drug washout period.

Conclusions: These effects on the electrophysiologic properties of cultured neurons are consistent with the concept that TPM exerts modulatory effects on voltage‐dependent Na+ and/ or Ca2+ conductances responsible for the generation and propagation of action potentials. Topiramate also may inhibit synaptic conductances responsible for transmission of epileptiform discharges.
Refractory Childhood Epilepsy and Factors Related to Refractoriness
Authors: Ohtsuka Yoko , Yoshinaga Harumi , Kobayashi Katsuhiro
Published: August 2005

Summary: To clarify the characteristics of refractory childhood epilepsy, we compared recent refractory cases and those of approximately 15 years ago, all of which were seen at the Okayama University Hospital. We also analyzed predictive factors related to refractoriness in the recent refractory cases. Among the recent refractory cases, the proportion of localization‐related epilepsies increased, and the proportion of generalized epilepsies decreased compared to historical cases. In generalized epilepsies, the proportion of cases with Lennox‐Gastaut syndrome decreased to less than half. In localization‐related epilepsies, the proportion of cases with frontal lobe epilepsy increased. The proportion of cases with unknown causes decreased to less than half. Of the cases with known causes, postencephalitis/postencephalopathy and focal cortical malformation, including tuberous sclerosis, accounted for most of the cases. More of the recent refractory cases were treated with high‐dose AED monotherapy, compared to more poly‐therapy in the cases of 15 years earlier. The following factors were related to future refractoriness: less than 1 year of age at onset of seizures, the presence of underlying pathology, status epilepticus, changes in type of epilepsy during the clinical course, and neonatal seizures. Regarding EEG findings of cases that had localization‐related epilepsies at the end of follow‐up, focal spike‐waves associated with diffuse spike‐waves on the first EEGs indicated future refractoriness.
Epilepsy in the Elderly
Authors: Hiyoshi Toshio , Yagi Kazuichi
Published: August 2005

Summary: Purpose: The aim of this study was to evaluate the clinical characteristics of elderly patients with epilepsy.

Methods: We retrospectively reviewed the clinical records of 190 patients (104 males and 86 females) aged 60 years or older at the time of study.

Results: Epilepsies were classified as generalized in 33 patients (17.4%), partial in 145 (76.3%), and undetermined in 12 (6.3%). Twenty‐nine of 33 patients with generalized epilepsy were idiopathic, whereas all patients with partial epilepsy were symptomatic. Symptomatic partial epilepsy (SPE) began at all ages (2 to 81 years). Patients with early onset (< 20 years) showed the most unfavorable course in both seizure control and social adaptability. Patients with late onset (50 years or older) had no family history of epilepsy, and half of them had a past history of ccrebrovascular disease or head injury as a presumed etiology. In patients with idiopathie generalized epilepsy (IGE), 25 of 29 had early onset, and a family history of epilepsy was found in 31%. Nineteen patients continued to have seizures after 50 years of age, albeit infrequently. Furthermore, 10 of them showed exacerbation around the age of 50.

Conclusions: Most of the late onset epilepsies were SPE with a relatively good prognosis. General belief has held that seizure outcome in IGE is favorable, but some IGE patients show an increased seizure propensity in old age.
A Psychosocial Approach to Epileptic Patients
Authors: Ogata Akira , Amano Kouichiro
Published: August 2005

Summary: A psychoeducational approach was taken with 174 epileptic patients. Using this approach, no family problems were recognized among patients with idiopathic generalized epilepsy (IGE) or among those with symptomatic generalized epilepsy (SGE). However, 11 patients with temporal lobe epilepsy (TLE) and 1 patient with non‐temporal lobe epilepsy (non‐TLE) did exhibit family problems indicating that such problems involving IGE or SGE cases can be prevented through educational programs using a psychoeducational approach. This fails, however, to prevent such problems for TLE or non‐TLE cases. Furthermore, small group psychotherapy was given to 10 patients with intractable TLE. They were directed to make self‐evaluations regarding therapeutic factors originally introduced by Yalom but specially modified for these particular patients. Relatively high evaluations were given on every factor when compared with the results of individual psychotherapy. These results point out the importance of providing such psychotherapeutic approaches as group psychotherapy and self‐help groups in addition to educational programs in order to enhance the quality of life (QOL) of epileptic patients and their families.
Development of complement therapeutics for inhibition of immune‐mediated red cell destruction
Authors: Yazdanbakhsh Karina
Published: July 2005

A major objective of my National Blood Foundation (NBF)‐funded proposal was to produce recombinant soluble forms of a complement regulatory protein called complement receptor 1 (CR1) that carries the Knops blood group system antigens to perform antibody neutralization studies. By generating these recombinant proteins, we were able to inhibit several Knops antibodies in patient serum samples, thereby demonstrating their usefulness for clinical use. Interestingly, the recombinant CR1 proteins generated through NBF funding were also found to strongly reduce complement‐mediated red cell destruction in a mouse hemolytic transfusion model. In this review, I will outline our NBF‐funded studies, give an overview of recent advances from our group and others in the development of complement therapeutics, and highlight their potential use in the transfusion medicine setting.
Assessment of the correlation of platelet morphology with in vivo recovery and survival
Authors: Mintz Paul D. , Anderson Garth , Avery Nancy , Clark Pamela , Bonner Robert F.
Published: July 2005

BACKGROUND:  There is continuing interest in the development of in vitro tests evaluating the in vivo function, recovery, and survival of platelets stored for transfusion. A recent forum concluded that no completely reliable test exists, although discoid morphology indicates a platelet's good health. We evaluated a novel device, the NAPSAC (Noninvasive Assessment of Platelet Shape and Concentration), designed to determine noninvasively the proportion of discoid platelets in a stored concentrate, as well as platelet concentration.

STUDY DESIGN AND METHODS:  Twenty‐eight plateletapheresis concentrates stored 24 hours in PL‐146 were evaluated. Percent discoid platelet results were correlated with radiolabeled autologous recovery and survival performed using 111Indium oxyquinoline and calculated using linear (L) and multiple‐hit (M) models. pH of 8 concentrates was raised at the end of storage with 6N NaOH. Platelet concentration measured by NAPSAC and Coulter Thrombocounter C was compared in 256 plateletapheresis products.

RESULTS:  Percent discoid platelets at 24 hours did not correlate significantly with platelet recovery or survival (recovery L = 0.29, M = 0.28; survival L = 0.16, M = 0.03). Raising the pH (mean 6.38 to 6.94) resulted in a significant increase in percent discoid platelets (21% to 41%). Platelet concentration values for both methods studied were linearly correlated with a slope of 1.01 ± 0.03, r = 0.81.

CONCLUSION:  Percent discoid platelets was not predictive of posttransfusion platelet recovery or survival. The results suggest that non‐discoid platelets may survive posttransfusion and even revert to discoid shape, since raising the pH approximately doubled the percent of discoid platelets. The NAPSAC was shown to be a reliable instrument for noninvasively determining platelet concentration in PL‐146 concentrates.
The effect of immunization on the response to P. gingivalis infection in mice is adjuvant‐dependent
Authors: Houri‐Haddad Yael , Soskolne W. Aubrey , Halabi Amal , Shapira Lior
Published: August 2005

Aim: Studies on vaccines against the periodontal pathogen Porphyromonas gingivalis have produced conflicting results, but no consideration has been given to the role of different adjuvants in these vaccines. We have previously shown that an intra‐chamber challenge with heat‐killed P. gingivalis was modified by immunization with different adjuvants. This study tested the hypothesis that different adjuvants in P. gingivalis vaccines would differentially modify the host response to a live P. gingivalis infection.

Results: Using P. gingivalis‐infected subcutaneous chambers in mice, we show that vaccination with P. gingivalis in alum attenuated the pro‐inflammatory cytokine levels at the site of infection, while the vaccine containing incomplete Freund's adjuvant did the opposite. Although both vaccines induced a similar humoral IgG response, P. gingivalis‐induced abscesses were significantly smaller in the alum‐adjuvant group.

Conclusions: The results suggest that the immune response and the resultant protection to a P. gingivalis infection, in P. gingivalis‐vaccinated mice, are adjuvant‐dependent.
Relating Consumer Willingness‐to‐Pay for Food Safety to Risk Tolerance: An Experimental Approach
Authors: Brown Jennifer , Cranfield John A. L. , Henson Spencer
Published: July 2005

This study investigates the role of risk tolerance in shaping Canadian consumers' willingness‐to‐pay for food safety risk reductions. Non‐hypothetical experimental auctions were used to elicit consumer valuations of food safety improvement. To identify the relationship between food safety concern and risk‐reduction valuations, individual risk‐perception scores are constructed based on questionnaire responses. Results show willingness‐to‐pay for improved food safety tends to decrease as individuals become more risk tolerant. Differences in bids across naïve and informed rounds of bidding tend to become smaller with risk tolerance for individuals who initially overestimated the food safety risk.
A Decomposed Negative Binomial Model of Structural Change: A Theoretical and Empirical Application to U.S. Agriculture
Authors: Kim C. S. , Schluter G. , Schaible G. , Mishra A. , Hallahan C.
Published: July 2005

We developed a single‐equation decomposed negative binomial regression model (NBRM) of the U.S. farm sector to simultaneously evaluate structural changes in the U.S. agricultural sector and the strength of several economic forces that influenced the changes in farm structure during the 1960–96 period. We found all these forces reinforced economic incentives to increase the size and decrease the number of small farms. Only agricultural programs and machinery prices countered these forces.

Nous avons élaboré un modèle de régression binomiale négative (NBRM) décomposéàéquation unique pour le secteur agricole des États‐Unis afin d'évaluer simultanément les changements structurels de ce secteur ainsi que la puissance de plusieurs forces économiques qui ont influencé les changements de structure des exploitations agricoles au cours de la période 1960–96. Nous avons conclu que toutes ces forces ont renforcé les stimulants économiques en faveur d'une augmentation de la taille des exploitations et d'une diminution du nombre de petites exploitations. Seuls les programmes agricoles et le prix de la machinerie ont contrecarré ces forces.
Short‐term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen
Authors: McConell Glenn K. , Lee‐Young Robert S. , Chen Zhi‐Ping , Stepto Nigel K. , Huynh Ngan N. , Stephens Terry J. , Canny Benedict J. , Kemp Bruce E.
Published: July 2005

We examined the effect of short‐term exercise training on skeletal muscle AMP‐activated protein kinase (AMPK) signalling and muscle metabolism during prolonged exercise in humans. Eight sedentary males completed 120 min of cycling at 66 ± 1%, then exercise trained for 10 days, before repeating the exercise bout at the same absolute workload. Participants rested for 72 h before each trial while ingesting a high carbohydrate diet (HCHO). Exercise training significantly (P < 0.05) attenuated exercise‐induced increases in skeletal muscle free AMP: ATP ratio and glucose disposal and increased fat oxidation. Exercise training abolished the 9‐fold increase in AMPK α2 activity observed during pretraining exercise. Since training increased muscle glycogen content by 93 ± 12% (P < 0.01), we conducted a second experiment in seven sedentary male participants where muscle glycogen content was essentially matched pre‐ and post‐training by exercise and a low CHO diet (LCHO; post‐training muscle glycogen 52 ± 7% less than in HCHO, P < 0.001). Despite the difference in muscle glycogen levels in the two studies we obtained very similar results. In both studies the increase in ACCβ Ser221 phosphorylation was reduced during exercise after training. In conclusion, there is little activation of AMPK signalling during prolonged exercise following short‐term exercise training suggesting that other factors are important in the regulation of glucose disposal and fat oxidation under these circumstances. It appears that muscle glycogen is not an important regulator of AMPK activation during exercise in humans when exercise is begun with normal or high muscle glycogen levels.
Presynaptic control of group Ia afferents in relation to acquisition of a visuo‐motor skill in healthy humans
Authors: Perez Monica A. , Lungholt Bjarke K. S. , Nielsen Jens B.
Published: July 2005

Sensory information continuously converges on the spinal cord during a variety of motor behaviours. Here, we examined presynaptic control of group Ia afferents in relation to acquisition of a novel motor skill. We tested whether repetition of two motor tasks with different degrees of difficulty, a novel visuo‐motor task involving the ankle muscles, and a control task involving simple voluntary ankle movements, would induce changes in the size of the soleus H‐reflex. The slope of the H‐reflex recruitment curve and the H‐max/M‐max ratio were depressed after repetition of the visuo‐motor skill task and returned to baseline after 10 min. No changes were observed after the control task. To elucidate the mechanisms contributing to the H‐reflex depression, we measured the size of the long‐latency depression of the soleus H‐reflex evoked by peroneal nerve stimulation (D1 inhibition) and the size of the monosynaptic Ia facilitation of the soleus H‐reflex evoked by femoral nerve stimulation. The D1 inhibition was increased and the femoral nerve facilitation was decreased following the visuo‐motor skill task, suggesting an increase in presynaptic inhibition of Ia afferents. No changes were observed in the disynaptic reciprocal Ia inhibition. Somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve (TN) were also unchanged, suggesting that transmission in ascending pathways was unaltered following the visuo‐motor skill task. Together these observations suggest that a selective presynaptic control of Ia afferents contributes to the modulation of sensory inputs during acquisition of a novel visuo‐motor skill in healthy humans.