bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy and Religious Experiences: Voodoo Possession
Authors: Carrazana E. , DeToledo J. , Tatum W. , Rivas‐Vasquez R. , Rey G. , Wheeler S.
Published: August 2005

Summary: Epileptic seizures have a historical association with religion, primarily through the concept of spirit possession. Five cases where epileptic seizures were initially attributed to Voodoo spirit possession are presented. The attribution is discussed within the context of the Voodoo belief system.
Quality‐of‐Life and Behavioral Outcome Measures in Randomized Controlled Trials of Antiepileptic Drugs: A Systematic Review of Methodology and Reporting Standards
Authors: Baker Gus A. , Hesdon Bernadette , Marson Anthony G.
Published: August 2005

Summary: Purpose: To review the methodology and use of quality‐of‐life and behavioral measures used in randomized controlled trials (RCTs) of antiepileptic drugs in patients with epilepsy.

Methods: Trial reports were found by searching a previously developed comprehensive database of epilepsy RCTs and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and quality‐of‐life and behavioral measure data were extracted.

Results: There were 52 different measures used in 46 trials, with the Profile of Mood States, the Minnesota Multiphasic Personality Inventory, and the Washington Psychosocial Seizure Inventory being applied the most frequently. Overall, evidence of the reliability, validity, and sensitivity of measures used in populations of people with epilepsy was sparse. There was also little information on the clinical interpretation of the results.

Conclusion: Our results highlight a consistent failure to apply quality‐of‐life and behavioral measures in RCTs in a systematic way. We found repeated evidence of researchers' failure to review the use of previous measures and selection of measures without evidence of their appropriateness for use in a population with epilepsy. We recommend the use of quality‐of‐life and behavioral measures in RCTs with proven psychometric properties in a population with epilepsy.
Moderators of the Effect of Preoperative Emotional Adjustment on Postoperative Depression After Surgery for Temporal Lobe Epilepsy
Authors: Derry Paul A. , Rose Kristopher J. , McLachlan Richard S.
Published: August 2005

Summary: Purpose: Other outcome measures besides seizure control must be considered when assessing the benefit of epilepsy surgery. We investigated the effect of preoperative psychosocial adjustment on postoperative depression in epilepsy patients followed up prospectively for 2 years after temporal lobectomy.

Methods: The Washington Psychosocial Seizure Inventory (WPSI) evaluated psychosocial functioning; the Centre for Epidemiological Studies Depression Scale (CES‐D) measured depression. Both were completed at baseline and follow‐up.

Results: Follow‐up occurred in 39 temporal lobectomy patients at 2 years after surgery. Greatest improvement in depression scores was limited to patients with good seizure outcomes (seizure free, or marked reduction in seizure frequency), and seizure outcome was a significant predictor of postoperative depression. Despite this, preoperative scores on the emotional adjustment scale of the WPSI were most highly correlated with depression 2 years after surgery. To clarify this relation, moderated hierarchic regression suggested that good preoperative emotional adjustment (WPSI) was generally associated with less depression after surgery. Moreover, poorer preoperative adjustment combined with older age, generalized seizures, the finding of preoperative neurologic deficits, a family history of psychiatric illness, and/or a family history of seizures was related to higher depression scores 2 years after surgery.

Conclusions: Depression after temporal lobectomy is dependent on a complex interaction of variables and can have a significant effect on indices of postoperative adjustment. The WPSI emotional adjustment scale may help to predict which patients are likely to be chronically depressed after surgery.
Negative Emotions in Children with Newly Diagnosed Epilepsy
Authors: Oostrom K. J. , Schouten A. , Olthof T. , Peters A. C. B. , Jennekens‐Schinkel A.
Published: August 2005

Summary: Purpose: To understand the emotional predicament in children with recently diagnosed idiopathic or cryptogenic epilepsy.

Methods: We used the well‐tried method of structured projection for the first time in children with epilepsy. Thirty‐six children with epilepsy, aged 7–15 years (mean age, 9.5 years) and in 35 control children aged 7–15 years (mean age, 9.4 years), attributed shame and guilt in relation to three types of situation (non‐illness related, illness related, and epilepsy related). Children were evaluated twice: shortly after diagnosis, before antiepileptic drug (AED) use and after an interval of 3 months.

Results: Children with epilepsy and healthy controls were similar in their way of attributing shame and guilt. However, the type of situation was of influence: Both children with epilepsy and healthy children attributed more shame to incompetence due to epilepsy than to incompetence due to other illnesses.

Conclusions: Increased affective problems in childhood epilepsy cannot be explained by excessive attribution of shame and guilt, affects known to be important precursors of psycho‐pathology, yet both healthy children and children with epilepsy attribute more shame to epilepsy than to other illnesses. Epilepsy is not like any other disease.
The Impact of Childhood Epilepsy on Neurocognitive and Behavioral Performance: A Prospective Longitudinal Study
Authors: Bailet Laura L. , Turk William R.
Published: August 2005

Summary: Purpose: To assess neurocognitive and behavioral performance in children with idiopathic epilepsy (CWE, n = 74), their siblings without epilepsy (control, n = 23), and children with migraine (CWM, n = 13), and to identify medical factors related to learning or behavioral problems in CWE.

Methods: Subjects, ages 8–13 years with IQs of ≥80, completed a neurocognitive test battery annually for ≤3 years. For CWE, age at seizure onset, most recent EEG results, seizure type, seizure frequency, current antiepileptic drug (AED), and most recent AED serum levels were documented at each visit.

Results: CWE and CWM had high rates of grade retention and placement in special education compared with sibling controls. CWE performed worse than controls on numerous neurocognitive variables. These differences persisted over time. CWE with abnormal EEGs scored lower than CWE with normal EEGs on reading and spelling measures, even with comparable IQs. Age at seizure onset, seizure type, and seizure frequency were not related to neurocognitive or behavioral test scores. CWE taking carbamazepine (CBZ) performed better than CWE taking valproate (VPA) on academic achievement measures, although the study lacked controls necessary to assess this finding thoroughly. CWM did not differ from CWE or controls in cognitive or academic achievement skills.

Conclusions: Long‐term risk of learning problems exists among CWE as compared with controls, even with normal IQs and well‐controlled seizures. Predicting learning problems in CWE based on medical factors remains elusive. Monitoring of educational progress and neurocognitive screening may be most effective in assessing academic risk for CWE.
Lateralizing Value of Asymmetric Tonic Limb Posturing Observed in Secondarily Generalized Tonic–Clonic Seizures
Authors: Kotagal Prakash , Bleasel Andrew , Geller Eric , Kankirawatana Pongkiat , Moorjani Bhagwan I. , Rybicki Lisa
Published: August 2005

Summary: Purpose: A striking asymmetry of limb posture occurs during secondarily generalized tonic–clonic (GTC) seizures wherein one elbow is extended while the other is flexed during the tonic phase of the GTC seizure. We have named this phenomenon asymmetric tonic limb posturing (ATLP) or the “Figure 4 Sign.”

Methods: Fifty‐nine secondarily GTC seizures from 31 patients with partial epilepsy who underwent successful epilepsy surgery were analyzed, in addition to another group of 64 GTC and generalized clonic seizures from 26 patients collected prospectively over a 7‐month period. Three observers reviewed these seizures blinded to the side of ictal EEG onset and other clinical data.

Results: The extended elbow was contralateral to the side of ictal onset in 35 of 39 patients who had ATLP during their seizures. The kappa index, a measure of interobserver agreement, was calculated, and ATLP was found to have very good agreement between observers.

Conclusions: In secondarily generalized tonic–clonic seizures, ATLP (Figure 4 Sign) may sometimes be only available lateralizing sign.
Effects of Circadian Regulation and Rest—Activity State on Spontaneous Seizures in a Rat Model of Limbic Epilepsy
Authors: Quigg Mark , Clayburn Hope , Straume Martin , Menaker Michael , Bertram Edward H.
Published: August 2005

Summary: Purpose: Circadian regulation via the suprachiasmatic nuclei and rest–activity state may influence expression of limbic seizures.

Methods: Male rats (n = 14) were made epileptic by electrical stimulation of the hippocampus, causing limbic status epilepticus and subsequent seizures. We monitored seizures with intrahippocampal electrodes in 12–12‐h light/dark (LD) cycles and in continuous dark (DD). We used radiotelemetry monitoring of activity to measure state and body temperature to determine circadian phase. Cosinor analysis and χ2 tests determined whether seizures occurred rhythmically when plotted by phase. State was defined as inactive or active in 10‐min epochs based on whether activity count was below or above a cut‐off value validated from video observation.

Results: In LD, the peak seizure occurrence was 14:59 h after circadian temperature peak (95% confidence limit, 13:37–16:19). Phasic seizure occurrence persisted in DD for 14:05 (12:31–15:38), p < 0.0001, against uniform mean distribution. In LD, 14,787 epochs contained 1,268 seizures; seizures preferentially occurred during inactive epochs (965 observed, 878 expected in proportion to the overall distribution of inactive versus active epochs; p < 0.001). In DD, 20,664 epochs contained 1,609 seizures; seizures had no preferential occurrence by state (999 observed, 1,025 expected; p = 0.16).

Conclusions: Limbic seizures occurred with an endogenous circadian rhythm. Seizures preferentially struck during inactivity during entrainment to the light–dark cycle.
Anterior Cingulate Gyrus Epilepsy: The Role of Ictal rCBF SPECT in Seizure Localization
Authors: San Pedro Elmer C. , Mountz James M. , Ojha Buddhiwardhan , Khan Adil A. , Liu Hong‐Gang , Kuzniecky Ruben I.
Published: August 2005

Summary: Purpose: The goal of this report is to demonstrate the utility of ictal brain single photon emission tomography (SPECT) in a 39‐year‐old man with complex partial seizures arising from the anterior cingulate gyrus. Seizures originating from the anterior cingulate gyrus are difficult to localize because they have variable ictal semiology, are usually brief, and have rapid cortical propagation.

Methods: Clinical neurologic examination, electroencephalography, extended video‐electroencephalography with scalp and sphenoidal electrodes, magnetic resonance imaging, computed tomography, and ictal brain SPECT with Tc‐99m HMPAO were performed to identify the seizure focus. The patient's regional cerebral blood flow (rCBF) findings were compared with those of eight normal controls, and changes in rCBF were assessed by comparing the patient's ictal scan with those of normal controls at rest by using statistical parametric mapping (SPM).

Results: Clinical and neurologic evaluations failed to demonstrate the epileptogenic focus. Ictal rCBF brain SPECT showed a focal region of hyperperfusion in the anterior cingulate gyrus. By using SPM, the ictal blood flow increase in the right anterior cingulate gyrus (x, y, z, –6, 42, 24 mm) was found to be statistically significant when compared with normal controls (z score, 4.88, p < 0.001). Subdural EEG recordings with intracranial electrodes positioned over this location confirmed that the cingulate gyrus was the origin of the seizures, and surgical resection resulted in >90% seizure reduction.

Conclusions: We concluded that ictal brain SPECT localization in conjunction with subdural electrode confirmation is a useful test in the presurgical evaluation of difficult to localize cingulate epilepsy.
Distinct Behavioral and EEG Topographic Correlates of Loss of Consciousness in Absences
Authors: Vuilleumier P. , Assal F. , Blanke O. , Jallon P.
Published: August 2005

Summary: Purpose: To describe the behavioral and EEG topographic correlates of absences with 3‐Hz generalized spike‐waves and partitioned impairment of consciousness.

Methods: Two adult women had so‐called “phantom” absences, characterized by brief and mild impairments of consciousness that were previously inconspicuous to both patient and physician. Neuropsychological examination was performed under video‐EEG monitoring during absence status. EEG topographic mapping of spike‐wave discharges was obtained in the two cases.

Results: Only mild attentional and executive disturbances were observed during absence status despite prolonged discharges. Spike‐wave bursts were associated with selective impairment in the initiation of response and self‐generated action, whereas short‐term storage of external information during discharges was fully preserved. This is consistent with a predominant involvement of frontomesial cortex demonstrated by topographic mapping of spike‐wave discharges in the two cases. By contrast, in two other patients with typical absences and a complete lack of retention for information given during the discharges, topographic mapping found a more lateral frontal involvement by spike‐wave activity.

Conclusions: Different types of absence seizures may impair distinct components of conscious behavior. A predominant involvement of frontomesial thalamocortical circuitry may underlie an “inconspicuous” disorder of consciousness as seen in phantom absences with selective loss of initiation and goal‐oriented behavior, whereas involvement of more lateral frontal areas in typical absences may additionally disrupt working memory processes.
Reduction of Benzodiazepine Receptor Binding is Related to the Seizure Onset Zone in Extratemporal Focal Cortical Dysplasia
Authors: Arnold Stephan , Berthele Achim , Drzezga Alexander , Tölle Thomas R. , Weis Serge , Werhahn Konrad J. , Henkel Anja , Yousry Tarek A. , Winkler Peter A. , Bartenstein Peter , Noachtar Soheyl
Published: August 2005

Summary: Purpose: Comparison of regional reduction of GABA receptor binding and seizure onset zone in patients with extratemporal epilepsy due to focal cortical dysplasia.

Methods: Two patients with frontal lobe epilepsy who remained seizure free after partial frontal lobe resection were investigated with magnetic resonance imaging, positron emission tomography (PET) with 18F‐fluoro‐deoxy‐glucose (FDG) and 11C‐flumazenil, subdural EEG‐video recordings, and post‐operative benzodiazepine (BDZ)‐receptor autoradiography.

Results: The area of reduced BDZ‐receptor binding as documented by preoperative flumazenil‐PET and postoperative BDZ‐receptor autoradiography corresponded to the seizure on‐set zone and was smaller than the interictal hypometabolism documented by FDG‐PET.

Conclusion: Flumazenil‐PET is a useful tool for localization of the epileptogenic zone in patients with extratemporal epilepsy caused by focal cortical dysplasia. Neuronal distribution of BDZ‐receptor density confirms in vivo flumazenil‐PET findings. The regional reduction of BDZ‐receptor binding in focal cortical dysplasia seems to be confined to the seizure onset zone and not to the extent of dysplastic cortex.
The Epilepsy of Emperor Michael IV, Paphlagon (1034–1041 A.D.): Accounts of Byzantine Historians and Physicians
Authors: Lascaratos J. , Zis P. V.
Published: August 2005

Summary: Purpose: Presentation of epilepsy suffered by Byzantine Emperor Michael IV, Paphlagon (who reigned from 1034 to 1041 A.D.) and the attitude of his contemporary society to his disorder.

Methods: Research into the accounts of Byzantine historians and chroniclers referring to the case of the emperor and Byzantine medical texts revealing the opinion of official medicine about the disorder.

Results: Byzantine historians and chroniclers provide detailed clinical descriptions of the seizures of Emperor Michael IV. Nearly all, expressing popular opinion, considered his disease to be demonic possession that constituted a form of divine punishment for the emperor's adultery and act of murder; his royal entourage continually attempted euphemistically to present this condition as a psychic disease. On the contrary, research into Byzantine medical texts reveals that the physicians, already from the 4th century, following Hippocratic tradition, believed that epilepsy was primarily a brain‐related disorder and based their treatment on this etiological principle.

Conclusions: From the study of the Byzantine histories and chronicles, it can be deduced that Emperor Michael IV, Paphlagon, suffered from generalized tonic‐clonic epileptic seizures. Despite the concept then held by well‐educated Byzantine doctors, who considered epilepsy a brain disorder, information indicates the deep prejudices of his social environment.
Autosomal Dominant Partial Epilepsy with Auditory Features: Description of a New Family
Authors: Michelucci R. , Passarelli D. , Pitzalis S. , Dal Corso G. , Tassinari C. A. , Nobile C.
Published: August 2005

Summary: Purpose: To report the clinical and genetic study of a new family with autosomal dominant partial epilepsy with auditory features (ADPEAF).

Methods: All the living affected members underwent a full clinical, neurophysiological, and magnetic resonance imaging (MRI) study. Genetic analysis was performed by typing their DNA with seven microsatellite markers previously found to cosegregate with ADPEAF on chromosome 10q24.

Results: The three living affected members had a childhood onset of rare and drug‐responsive tonic‐clonic seizures constantly preceded by a humming sensation. Routine and sleep electroencephalograms revealed rare and inconstant focal abnormalities over both temporal regions. MRI detected atrophy with increased T2 signal in the subcortical lateral portion of the right temporal lobe in one case. Analysis of 10q24 polymorphic alleles showed the same haplotype in all three affected members but different alleles in unaffected individuals.

Conclusions: ADPEAF is a distinct condition with homogeneous clinical features. Genetic findings are consistent with linkage of ADPEAF to chromosome 10q24.
Familial Aphasic Episodes: Another Variant of Partial Epilepsy with Simple Inheritance?
Authors: Kanemoto Kousuke , Kawasaki Jun
Published: August 2005

Summary: We report on a family having partial epilepsy with simple inheritance. The affected members commonly have aphasic episodes with secondary generalization; onset occurred either in adolescence or adulthood. Patients' response to medication has varied greatly. No neurological defects or decline in intelligence were found. The case represents another variety of rare familial partial epilepsy with neocortical epilepsy features.
Effects of Lamotrigine on Field Potentials and Long‐Term Potentiation in Guinea Pig Hippocampal Slices
Authors: Langosch Jens Michael , Zhou Xiao‐Yan , Frick Alex , Grunze Heinze , Walden Jörg
Published: August 2005

Summary: Purpose: To investigate the effects of lamotrigine (LTG), a new anticonvulsant, on neuronal excitability, synaptic transmission, and long‐term potentiation (LTP) in guinea pig hippocampal slices.

Methods: Electrically evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were investigated in the CA1 region of the hippocampus.

Results: The concentration–response curves showed different actions of LTG in concentrations near therapeutic plasma levels (10 μM) on fEPSPs and PSs. The initial slopes of fEPSPs were not affected, whereas the amplitudes of PSs were significantly decreased. Higher concentrations of LTG decreased both fEPSP slopes and PS amplitudes; however, the effects on PSs were much stronger. Also, there were no differences in fEPSP slopes or PS amplitudes compared with controls when LTP was induced in the presence of LTG (10 μM).

Conclusions: Our data are in contrast to previous findings that suggest LTG acts primarily on presynaptic sites by blocking the release of excitatory amino acids. Further, LTP was not affected by LTG.
Genetic Localization of the Ca2+ Channel Gene CACNG2 Near SCA10 on Chromosome 22q13
Authors: Burgess Daniel L. , Matsuura Tohru , Ashizawa Tetsuo , Noebels Jeffrey L.
Published: August 2005

Summary: Purpose: Voltage‐dependent calcium channel mutations have been associated with spinocerebellar ataxia in humans (SCA6) and with ataxia, progressive cerebellar degeneration, and epilepsy in mice (tottering, lethargic, and stargazer). A novel autosomal dominant spinocerebellar ataxia syndrome with epilepsy (SCA10) was recently mapped to chromosome 22q13. The human ortholog of the mouse stargazer locus, the calcium channel γ subunit gene CACNG2, also is located in this region. Because the phenotypes of stargazer mice and SCA10 patients were similar, consisting of both cerebellar ataxia and seizures, we hypothesized that CACNG2 was a likely candidate for the SCA10 locus.

Methods: Polymerase chain reaction (PCR) based assays were developed for two polymorphic microsatellite markers near CACNG2. The location of CACNG2 was determined by linkage and haplotype analysis of the genotypes of 22 individuals from a human pedigree segregating SCA10.

Results: SCA10 was previously localized distal to marker D22S1177 on chromosome 22q13. We determined that CACNG2 was linked to D22S283 and D22S1177 with the marker order: centromere‐D22S283‐bcmDLB1 (CACNG2)–D22S1177‐D22S423‐telomere. Thus CACNG2 is located proximal to the SCA10 recombinant interval.

Conclusions: Here we report the first genetic linkage of CACNG2 on chromosome 22q13 and exclude it as a candidate for SCA10. In addition, our data clarify the relation between the physical and genetic linkage maps of this region and will facilitate isolation of the SCA10 gene.
Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices
Authors: Armand V. , Rundfeldt C. , Heinemann U.
Published: August 2005

Summary: Purpose: The objective of this study was to evaluate the effect of a new antiseizure drug, retigabine (D‐23129; N‐(2‐amino‐4‐[fluorobenzylamino]‐phenyl) carbamic acid ethyl ester) on low‐Mg2+‐induced epileptiform discharges in rat in vitro.

Methods: Three types of epileptiform discharges (recurrent short discharges in the hippocampus, seizure‐like events, and late recurrent discharges in the entorhinal cortex) were elicited in rat combined entorhinal cortex‐hippocampal slices by perfusion with low‐Mg2+‐artificial cerebrospinal fluid (ACSF). The antiepileptic properties of retigabine were evaluated as effect on the frequency and amplitude of the epileptiform activities as well as time of onset of the effect in the entorhinal cortex (EC) and in hippocampal area CA1 (CA1) by using extracellular recording techniques.

Results: Retigabine (20 μM) reversibly suppressed the recurrent short discharges otherwise sensitive only to high doses of valproate (VPA) but insensitive to standard antiepileptic drugs (AEDs) in CA1, whereas 10 μM reduced the frequency of discharges by 34 ± 18.8%, with no significant effect on the amplitude. In EC, retigabine (50 μM) reversibly suppressed the seizure‐like events, whereas μM blocked seizure‐like events in 71.5% of the slices. The seizure‐like events were also sensitive to standard AEDs. Late recurrent discharges in EC that are not blocked by standard AEDs were reversibly suppressed by retigabine (100 μM), whereas 50 μM reduced the frequency of the discharges by 94.4 ± 7.7%, and 20 μM, by 74.2 ± 18.0%, with no significant effect on the amplitude.

Conclusions: Retigabine is an effective AED with suppressive effects on recurrent short discharges and on late recurrent discharges normally insensitive to standard AEDs.
The Stigma of Epilepsy: A European Perspective
Authors: Baker Gus A. , Brooks Jayne , Buck Debbie , Jacoby Ann
Published: August 2005

Summary: Purpose: To study the stigma of epilepsy in a European sample.

Methods: Clinical and demographic details and information about patient‐perceived stigma was collected by using self‐completed questionnaires mailed to members of epilepsy support groups.

Results: Stigma data were collected from >5,000 patients living in 15 countries in Europe. Fifty‐one percent reported feeling stigmatised, with 18% reporting feeling highly stigmatised. High scores were correlated with worry, negative feelings about life, long‐term health problems, injuries, and reported side effects of antiepileptic drugs (AEDs). Cross‐cultural comparisons revealed significant differences between countries. A multivariate analysis identified impact of epilepsy, age of onset, country of origin, feelings about life, and injuries associated with epilepsy as significant contributors on scores on the stigma scale.

Conclusions: This study confirms the findings of previous studies that have identified the importance of both clinical and nonclinical factors in understanding the stigma of epilepsy. The results of cross‐cultural differences require further explanation, and much more research should be conducted to reduce the stigma associated with epilepsy.
Adverse Effects of Antiepileptic Drugs
Authors: Greenwood Robert S.
Published: August 2005

Summary: Because the efficacies of antiepileptic drugs (AEDs) are often equivalent, selection of an AED is often determined by adverse effects. Differences in methods for labeling adverse effects and in the adverse effect terms themselves, variations in the populations studied, and inconsistent classifications of adverse effects make it difficult to know how to use information on adverse effects to choose an AED. Effort is underway to develop more extensive and internationally acceptable descriptive terms for adverse effects. Comparison of adverse effects in patients taking AEDs with adverse events in control groups is helpful; however, data from controlled studies are often lacking for most AEDs. Because of these limitations, the clinician must adopt a preventative and early detection approach based on some general principles. This review outlines factors to consider for avoiding and detecting AED adverse effects. The occurrence of weight change with AEDs is reviewed extensively, serving to illustrate how the principle factors can be used to avoid and manage adverse effects and where there is need for better studies of the short‐ and long‐term adverse effects of AEDs.
The Effects of Epilepsy and Its Treatment on Sexual and Reproductive Function
Authors: Penovich Patricia E.
Published: August 2005

Summary: Male and female sexuality and reproductive functions are complex systems with cortical, limbic system, hypothalamic, pituitary, and end organ interactions. Sexual steroids are produced in the sexual glands, the adrenals, and the brain. They undergo interconversion in the brain, bind to different brain areas, and have multiple effects behaviorally and neuro‐physiologically. Progesterone, estrogen and testosterone have neuroendocrine effects that alter epileptogenicity. Seizure frequency may change throughout the life cycle as a result of hormonal status. Changes in central control, peripheral hormone levels, and/or medication effects may all contribute to decreased libido, potency, and fertility. Antiepileptic drugs (AEDs) interact with hormone‐binding metabolism, resulting in altered human reproductive function. AEDs alter contraceptive hormone treatments. Information on the effects of new AEDs is being gathered by the National Pregnancy Registry. Catamenial epilepsy and some sexual dysfunction in men may be treatable.
From Clinical Observation to Long‐Term Monitoring: Diagnostic Developments in Conservative Epileptology
Authors: Ried Sibylle , Hilfiker Peter , Mothersill Ian William , Krämer Günter
Published: August 2005

Summary: The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary‐level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long‐term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17·8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, ties, or startle reactions, are frequent (34·9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.
Multiple Pilocarpine‐Induced Status Epilepticus in Developing Rats: A Long‐Term Behavioral and Electrophysiological Study
Authors: Santos N. F. , Marques R. H. , Correia L. , Sinigaglia‐Coimbra R. , Calderazzo L. , Sanabria E. R. G. , Cavalheiro E. A.
Published: August 2005

Summary: Purpose: Animal models are useful for the study of status epilepticus (SE)‐induced epileptogenesis and neurological sequelae, especially during early brain development. Here, we show several permanent abnormalities in animals subjected to multiple SE during early development.

Methods: Wistar pup rats (7 to 9 days old) were subjected to three consecutive episodes of SE induced by systemic pilocarpine injections. To study the long‐lasting consequences of early‐induced SE, chronic electroencephalographic recordings were made from the hippocampus and cortex and several behavioral tests (inhibitory step‐down avoidance, rota‐rod, open field, elevated plus‐maze, and Skinner box) were performed at postnatal days 30 to 90. We also investigated in vitro electrophysiological responses of the CA1 area using extracellular recordings in hippocampal slices. A histological analysis was done using cresyl violet staining 24 hours and several months after SE induction. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL staining) 24 hours after the last SE episode.

Results: Electroencephalographic recordings from 30‐ to 90‐day‐old rats that had been subjected to multiple SE episodes in early life showed marked changes compared with those from nontreated controls. These included frequent episodes of continuous complex spiking activity and high‐voltage ictal discharges, with a small percentage of these rats presenting spontaneous behavioral seizures. These animals also presented evidence of severe cognitive deficit in adulthood. In vitro, a persistent hyperexcitability of the CA1 area was detected in experimental animals. Histological analysis of the brains did not reveal any major long‐term pathological changes. Nevertheless, an increased number of TUNEL‐positive nuclei were present in some animals in both the hippocampus and the thalamus.

Conclusions: These data show persistent abnormalities in animals subjected to multiple SE episodes during early postnatal development. SE may result in important plastic changes in critical periods of brain maturation leading to long‐lasting epileptogenesis, as manifested by electrographic epileptiform discharges, behavioral deficits, and in vitro hyperexcitability of hippocampal networks.
Endogenous Control of Hippocampal Epileptogenesis: A Molecular Cascade Involving Brain‐Derived Neurotrophic Factor and Neuropeptide Y
Authors: Reibel Sophie , Larmet Yves , Carnahan Josette , Marescaux Christian , Depaulis Antoine
Published: August 2005

Summary: Purpose: Seizures increase the expression of brain‐derived neurotrophic factor (BDNF) in the hippocampus. Because this neurotrophin exerts modulatory effects on hippocampal neuronal excitability, it may play an important role in epileptogenesis initiated in this structure. Moreover BDNF is known to regulate the expression of neuropeptide Y (NPY), which displays modulatory properties on seizure activity. This suggests that the effects of BDNF on epileptogenesis may be mediated by NPY.

Methods: Adult male rats received a 7‐day chronic intrahippocampal infusion of BDNF, BDNF antisense oligodeoxy‐nucleotides, NPY, or anti‐NPY immunoglobulin G during kindling of the hippocampus. The long‐term regulation of NPY expression by BDNF was also studied by immunohistochemistry and radioimmunoassay.

Results: BDNF applied during the first week of hippocampal stimulation significantly delayed the progression of kindling, an effect that outlasted the end of the infusion by at least 7 days. Conversely, infusion of BDNF antisense oligodeoxynucleotides to reduce the expression of endogenous BDNF in the hippocampus aggravated the electroencephalographic expression of seizures. Chronic infusion of BDNF increased the expression of NPY in the hippocampus, with a time course similar to that of the protective effect of the neurotrophin on kindling. Finally, chronic infusion of NPY in the hippocampus delayed the progression of hippocampal kindling, whereas anti‐NPY antibodies had an aggravating effect.

Conclusions: Our results suggest that the seizure‐induced increase in BDNF expression in the hippocampus may constitute an endogenous protective mechanism able to counteract hippocampal epileptogenesis. This protective effect appears to be mediated at least in part through the regulation of NPY expression.
Functional and Molecular Properties of Human Astrocytes in Acute Hippocampal Slices Obtained from Patients with Temporal Lobe Epilepsy
Authors: Schröder Wolfgang , Hinterkeuser Stefan , Seifert Gerald , Schramm Johannes , Jabs Ronald , Wilkin G. P. , Steinhäuser Christian
Published: August 2005

Summary: Purpose: The specific role of glial cells in epilepsy is still elusive. In this study, functional properties of astrocytes were investigated in acute hippocampal brain slices obtained from surgical specimens of patients with drug‐resistant temporal lobe epilepsy (TLE).

Methods: The patch‐clamp technique together with a single‐cell reverse transcription–polymerase chain reaction approach were used to combine functional and molecular analysis in the same individual cell in situ.

Results: In patients with Ammon's horn sclerosis, the glial current patterns resembled properties of immature astrocytes in rodent hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin‐sensitive Na+ currents. Hyperpolarizing voltages elicited inward rectifier K+ currents. Comparative recordings were made in astrocytes from patients with lesion‐associated TLE that lacked significant histopathological hippocampal alterations. The inward rectifier K+ current density was significantly smaller in astrocytes from the sclerotic group compared with lesion‐associated TLE patients.

Conclusions: During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears that astrocytes in human sclerotic tissue reexpress an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure‐induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity‐dependent K+ release and may thus contribute to seizure generation and spread in this particular condition of human TLE.
Developmental and Therapeutic Pharmacology of Antiepileptic Drugs
Authors: Miura Hisao
Published: August 2005

Summary: We investigated the clinical effects and plasma levels of zonisamide (ZNS) in children with cryptogenic localization‐related epilepsies. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half‐life is long as compared with that of other common antiepileptic drugs. The peak‐to‐trough plasma level ratios during a day were as small as 1.28 ± 0.15 in children taking a daily dose of 8 mg/kg of ZNS once a day as a single drug. The plasma level (μg/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels both increased with advancing age, but the peak‐to‐trough plasma level ratios were maintained almost uniformly throughout the pediatric age period. A wide range of the plasma levels was associated with complete freedom from seizures. The range of the plasma levels in patients who did not respond to ZNS was higher than that in the controlled group. However, the clinical effects of ZNS were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15–40 μg/ml. Any patient who receives polytherapy is at risk to develop 1 or more drug interactions. Concurrent administration of carbamazepine (CBZ) decreases plasma concentrations of ZNS. However, ZNS does not alter plasma concentrations of CBZ or its primary metabolite, carbamazepine‐10,11‐epoxide (CBZ‐E). It is evident that the concurrent administration of lamotrigine (LTG) affects plasma concentrations of CBZ‐E, while plasma CBZ levels remain unaltered. However, the effect of LTG on plasma concentrations of CBZ‐E is small, and none of the study patients showed toxic plasma concentrations of CBZ‐E or associated clinical toxicity. Drug‐protein binding interactions are another source of side effects. A simultaneous administration of valproic acid increases the total plasma CBZ‐E levels relative to the CBZ dose associated with the raised free fractions of CBZ and CBZ‐E. The high free plasma concentrations of CBZ‐E above 1.5 μg/ml may be responsible for the side effects.
Surgical Indication for Refractory Childhood Epilepsy
Authors: Oguni Hirokazu , Mukahira Kyoko , Tanaka Teruyuki , Awaya Yutaka , Saito Kayoko , Shimizu Hiroyuki , Oda Masaya , Arai Nobutaka , Suzuki Ichiro , Osawa Makiko
Published: August 2005

Summary: Recent progress in surgical intervention for medically refractory epilepsy has helped to shed light on more complex epileptogenic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well defined. The developing child with a seizure disorder has several problems that are different from adults, such as neural plasticity, deleterious effects of seizures on developmental status, and spontaneous resolution of epilepsy. The critical age for irreversible brain dysfunction and the timing of surgery are the main issues for the treatment of children. Thus, earlier surgical intervention is generally recommended to prevent further deterimental seizure effects, but we still do not know the optimal age. Until the establishment of guidelines for pediatric epilepsy surgery, surgical indications should be determined by the prognosis and the presence of a resectable epileptogenic focus, which in turn are based on the localization of the epileptic focus, seizure frequency, severity, and cognitive function of each case, rather than just the patient's age.
Molecular Genetic Study on Angelman Syndrome Patients without a Chromosomal Deletion
Authors: Saitoh Shinji , Wada Takahito , Sakai Taeko , Kobayashi Norio
Published: August 2005

Purpose: Angelman syndrome (AS) is a ncurobehavioral disorder characterized by severe mental retardation, easily cvoked laughter, ataxic gait, and epilepsy. Epilepsy associated with AS is characterized by early childhood onset gencralized seizures with profound EEG abnormalities. Therefore, AS is a good human model for genetic epilepsy syndromes. Approximately 70% of AS cases are caused by maternal deletions of chromosomc 15q I I‐qI3; whereas, 30% are not associated with a chromosomal dcletion. Thcse non‐deletion AS patients are caused by paternal uniparental disomy (UPD), imprinting mutation (IM), or loss‐or‐function mutations of the UBE3A gene, cach of which predisposes different recurrence risk. To elucidate molecular etiology of non‐dclction AS patients, we investigated 34 AS patients without a chromosomal deletion.

Methods: Thirty sporadic AS patients, and 4 familial AS patients (2 families of 2 sibs) were enrolled to the study. The diagnosis of AS was based on Williams’ criteria (Williams et al., Am J Med Genet 1995, 56: 237). Genomic DNA was extracted from peripheral blood by a standard procedure. DNA mcthylation tcst at SNRPN locus and genotyping using 7 highly informative PCR‐based polymorphisms within 15q I I ‐ q I3 were carried out to identify UPD and IM. When both UPD and IM were ruled out, the patients were classified :LS non‐UPD, non‐IM. For thcsc non‐UPD, non‐1M paticnts, UBE3A mutations were screened by PCR‐SSCP analysis using 10 sets ofprimcrs covering all coding exons.

Results: Among 30 sporadic patients, I UPD and 3 IM patients were identified, and the remaining 26 patients were classified as non‐UPD, non‐IM. Among 4 familial patients, 2 sibs from I family were detected as IM, whcrcas 2 sibs from another family were classified as non‐UPD, non‐IM. No UBE3A mutations were identified within 26 sporadic and 2 familial non‐UPD, non‐IM patients.

Conclusion: Threc molecular classes were identified for noindeletion AS patients. Therefore, the underlying genetic mechanism was dcmonstratcd to be complex for AS patients without a chromosomal deletion. Combination of the DNA methylation test and PCR‐based polymorphisms was sufficient to detect UPD and IM patients. Because recurrence risk is low for UPD and high lor IM, systematic molecular investigation including the DNA methylation test and PCR‐based polymorphisms should bc donc for non‐delction AS paticnts for genetic counscling purpose. A majority of non‐deletion patients were classified as noii‐UPD, non‐1M. Although, approximate 30% of non‐UPD, nonIM patients arc rcportcd to have UBE3A mutations, no such mutations were identified in our study. An underlying molecular mechanism was not rcvealcd for this group of patients, and therefore, assessment of recurrence risk was difficult. Further investigation is necessary for noii‐UPD, non‐1M paticnts.
Changes in Serum Phenytoin Concentrations in Epileptic Patients Produced by Changing Phenytoin Preparation from Granular Form to a Novel 10% Powder.
Authors: Emori Kenji , Okabe Akihito , Tanaka Kodai , Tajiri Koji , Kurachi Masayoshi
Published: August 2005

Purpose: It is well known that there is a significant difference in the bioavailability of different preparations of phenytoin (PHT). A novel 10 % powder formulation of PHT (Aleviatino‐10 % powder), which was believed to have equivalent bioavailability to the tablet and granular formulations, was developed by Dainippon Pharmaceutical Co., LTD. in 1997. This lead us to switch 12 outpatients with epilepsy from the granular preparation of PHT (Aleviatino‐granules) to the novel 10 96 powder. Here, we report that changing the PHT formulation from the granular to the novel powder form produced a significant change in hioavailability.

Methods: Subjects consisted of 8 men and 4 women with epilepsy; mean age, 32.7 years; range, 21–58 years; 2 generalized epilepsies and 10 localization‐related epilepsies recruited from the outpatient clinics. The dose of the granular form of PHT was 90‐390 mg/day (mean, 258.3 mg/day). Four patients received only PHT and the remaining patients received PHT and at least 1 other AED. The serum PHT concentrations were determined prior to and more than 2 weeks after changing the formulations. We used the same dose for each preparation, and the dose of any other anticonvulsant drug taken by the patients was not changed during the study. Results: The mean serum PHT level was significantly elevated from 9.66 to 19.51 pg/ml after switching the patients to the 10% powder formulation (p < 0.01). The mean ratio of serum PHT concentrations (S, pg/ml) to dose (D, mgikgiday), i.e. S/D ratio, was also increased significantly from 2.1 to 4.3 after switching preparations (p < 0.01). A decrease in the dose (mean, 85 %) was required in 6 patients. There was a significant positive correlation between extent of the elevation of serum PHT concentration after switching to the 10 % powder and serum PHT concentration before the switch (r = 0.86, p c 0.0003). Furthermore, the elevation of serum PHT levels in the patients receiving only PHT was significantly greater than that in the patients receiving 1 or more other anticonvulsants (p < 0.05).

Cuncbsion: These results suggest that the 10% powder formulation of PHT (Aleviatino‐10% powder) has a significantly greater bioavailability than the granular form (Aleviatino‐granules). Therefore, one must be vigilant when switching patients from one formulation of PHT to another, particularly in patients receiving only PHT. In addition, upon switching, one should consider adjusting the dose to decrease the likelihood of adverse effects and interactions between PHT and other anticonvulsants.