bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Statistical Parametric Mapping and SPECT Difference Imaging in Patients with Temporal Lobe Epilepsy
Authors: Chang David J. , Zubal I. George , Gottschalk Chris , Necochea Alejandro , Stokking Rik , Studholme Colin , Corsi Maria , Slawski Jessica , Spencer Susan S. , Blumenfeld Hal
Published: March 2003

Summary:  Purpose: Statistical parametric mapping (SPM) is an image‐analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel‐by‐voxel basis, thereby removing the subjectivity inherent in conventional region‐of‐interest (ROI) analysis. Our platform of single‐photon emission computed tomography (SPECT) ictal–interictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study.

Methods: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group.

Results: The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods.

Conclusions: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal–interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy.
Memory Outcome after Selective Amygdalohippocampectomy: A Study in 140 Patients with Temporal Lobe Epilepsy
Authors: Gleissner Ulrike , Helmstaedter Christoph , Schramm Johannes , Elger Christian E.
Published: March 2003

Summary:  Purpose: The technique of selective amygdalohippocampectomy (SAH) was originally developed in epilepsy surgery to spare unaffected brain tissue from surgery, thus minimizing the cognitive consequences of temporal lobe surgery. The results of previous studies, however, are equivocal in this regard. This study evaluated memory after SAH in a large sample of patients with mesial temporal lobe epilepsy.

Methods: The 140 patients received material‐specific memory tests before and 3 months after unilateral SAH.

Results: Significant declines in all aspects of verbal learning and memory were found particularly for the left resected group. With reliability‐of‐change indices, a high number of patients showed postoperative verbal memory declines, ≤51% in left SAH and ≤32% in right SAH. For left SAH, a higher preoperative verbal memory performance, a lower preoperative nonverbal memory score, an older age at surgery, and a later onset of epilepsy predicted a stronger decline in verbal memory. After right SAH, the risk for a verbal memory decline was slightly increased when patients had surgical complications or a presurgical evaluation with bilateral intrahippocampal depth electrodes. Results concerning nonverbal memory were less clear.

Conclusions: The results clearly indicate, that particularly left SAH can lead to a significant decline in memory functions. Predictors of postoperative verbal memory were similar to those reported for temporal lobectomy. Postoperative deteriorations were broader and stronger in our study than in previous studies. We discuss methodologic differences (sample size, retest interval, extent of resection) and other factors as possible reasons.
Temporal Lobe Epilepsy in Children: Etiology in a Cohort with New‐onset Seizures
Authors: Sztriha László , Gururaj Aithala K. , Bener Abdulbari , Nork Michael
Published: March 2003

Summary:  Purpose: The aim of this study was to characterize the incidence and etiology of temporal lobe epilepsy (TLE) in a community‐based cohort of children with new‐onset disease.

Methods: A community‐based cohort of 30 children with TLE was studied. The patients had new‐onset disease before age 14 years between 1995 and 1999. They underwent clinical, EEG, and magnetic resonance imaging investigations.

Results: The patients could be divided in three main groups according to likely etiology, as suggested by Harvey et al. (Neurology 1997;49:960–8). Group 1 consisted of eight (26.7%) children with malformations or long‐standing, nonprogressive tumors (developmental TLE). Arachnoid cysts were found in three, dual pathology [cortical dysplasia and hippocampal sclerosis (HS)] in one, and focal cortical dysplasia with glioproliferative changes in one patient. Dysembryoplastic neuroepithelial tumor was responsible for the epilepsy in one, and ganglioglioma, in two children. Group 2 consisted of seven (23.3%) children with a significant antecedent and/or HS. Five children had a significant illness or event before the onset of TLE, including perinatal hypoxic–ischemic encephalopathy in one, encephalitis in one, traumatic brain injury in two, and complex febrile seizures in one. HS was found in the patients with traumatic brain injury and complex febrile seizures in the history in addition to two children without known antecedents. Group 3 comprised 15 (50%) children with no abnormality on neuroimaging and no significant antecedents (cryptogenic TLE).

Conclusions: Etiologic differences between children with new‐onset TLE may have prognostic implications: children with TLE and significant antecedents/HS are expected to have the greatest risk of continued seizures and psychological problems.
Interictal Epileptiform Discharges Do Not Change before Seizures during Sleep
Authors: Natarajan Alamelu , Marzec Mary L. , Lin Xihong , Minecan Daniela , Malow Beth A.
Published: March 2003

Summary:  Purpose: Whether interictal epileptiform discharges (IEDs) increase, decrease, or are unchanged before epileptic seizures has implications for the pathophysiology of epilepsy. Prior studies relating IEDs and seizures have not demonstrated a change in IEDs before seizures. However, they have not controlled for changes in the depth of sleep. Our objective was to test the hypothesis that IEDs are related to seizures during sleep while adjusting for log delta power (LDP), a continuous measure of sleep depth.

Methods: Twenty‐two seizures during sleep were identified in 16 subjects with epilepsy admitted for presurgical monitoring. The IEDs that occurred in the hour of sleep before each seizure were used to test the relation between IEDs and seizure occurrence. Sleep depth was measured by LDP (quantity of 1‐ to 4‐Hz activity in 30‐s epochs), and records were scored visually for sleep staging and for IEDs. Multivariate logistic regression analyses were applied.

Results: Adjusting for LDP, number of seizures before the current seizure, quartile of the night, and total number of IEDs that occurred during the night, IED did not increase or decrease before seizures (p > 0.1). The rate of IEDs increased directly with LDP (p = 0.0001), as shown in prior work.

Conclusions: IEDs are not activated or suppressed before seizures during sleep, suggesting that different pathophysiologic processes underlie these two phenomena. These results corroborate prior studies, while providing a more advanced analysis by adjusting for sleep depth and applying multivariate logistic regression analyses.
Epidemiologic Features of Infantile Spasms in Slovenia
Authors: Primec Zvonka Rener , Kopač Štefan , Neubauer David
Published: March 2003

Summary:  Purpose: To determine the epidemiologic features of infantile spasms (ISs) in Slovenia.

Methods: Medical records of all children with ISs in Slovenia in the period from 1985 to 1995, based on community pediatrician referrals to four hospitals, including all pediatric EEG laboratories, were retrospectively studied. The outcome was assessed by a follow‐up study in 1998.

Results: Forty‐seven children with ISs were identified over an 11‐year interval. The cumulative incidence was 2.06 per 10,000 live births. Among 29 (61.7%) children with symptomatic etiology, 14 cases had prenatal etiology [tuberous sclerosis (TS), seven; vascular insult, three; cerebral malformations, three; Down syndrome, one child], 14 perinatal and one postnatal cause: anoxic brain damage after cardiac surgery. Cryptogenic and idiopathic etiology were diagnosed in 13 (27.6%) and five (10.6%) of 47 cases, respectively. The age of onset of ISs ranged from 2 to 10 months. As initial treatment, steroids were used in 19 children (remission in 10); vigabatrin in seven (remission in four), and other antiepileptic drugs (AEDs) in 20 children (remission in six). According to the follow‐up study, 18 (38.3%) children were seizure free, and 14 of them had normal mental development. Among 29 mentally retarded children (14 severely), 26 belonged to the symptomatic group. Four children died.

Conclusions: The incidence of ISs in Slovenia is similar to that in some parts of the United States, but lower than that in Finland or Sweden. The outcome depends mainly on etiology. Additional neuroimaging studies are needed for evaluation of cryptogenic cases.
Multiple Subpial Transection for Intractable Partial Epilepsy: An International Meta‐analysis
Authors: Spencer Susan S. , Schramm Johannes , Wyler Allen , O'Connor Michael , Orbach Darren , Krauss Gregory , Sperling Michael , Devinsky Orrin , Elger Christian , Lesser Ronald , Mulligan Lisa , Westerveld Michael
Published: March 2003

Summary:  Purpose: Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected.

Methods: A meta‐analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty‐three patients underwent MST without resection.

Results: In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%).

Conclusions: These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand‐alone procedure to allow further development of criteria and predictive factors for outcome.
A Rett Patient with a Typical Angelman EEG
Authors: Laan Laura A. E. M. , Vein A. A.
Published: March 2003

Summary:  Purpose: To draw attention to the phenomenon that EEG characteristics of both Angelman syndrome (AS) and Rett syndrome (RS) can be found in the same patient, as evidenced by the description of one case. There are specific EEG patterns in AS patients, in which the most frequently occurring EEG characteristics are rhythmic triphasic 2‐ to 3‐Hz, high‐voltage (200–500 μV) activity, mixed with spikes or sharp waves, with a maximum over the frontal regions. EEG changes in RS patients are less specific and can show multifocal, mostly central or centrotemporal epileptiform discharges in combination with slow background activity.

Methods: A 6‐year‐old girl with RS and a proven MECP2 mutation was described.

Results: She had an EEG pattern at age 2 years comparable with the clinical diagnosis of RS, and an EEG at age 6 years comparable with an AS EEG.

Conclusions: We wish to draw attention to this phenomenon, although there is as yet no evident explanation for it. We advise MECP2 examination in AS patients of unknown genetic etiology whose EEG examinations are/were pathognomonic for AS to exclude RS.
Focal Cortical Dysplasia of Taylor's Balloon Cell Type: A Clinicopathological Entity with Characteristic Neuroimaging and Histopathological Features, and Favorable Postsurgical Outcome
Authors: Urbach Horst , Scheffler Björn , Heinrichsmeier Thomas , Von Oertzen Joachim , Kral Thomas , Wellmer Joerg , Schramm Johannes , Wiestler Otmar D. , Blümcke Ingmar
Published: March 2003

Summary: Background and Purpose: Focal cortical dysplasia of Taylor's balloon‐cell type (FCD‐BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD‐BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery.

Methods: From an epilepsy data bank with 547 histological specimens, 17 FCD‐BC were re‐evaluated of which high resolution MRI was available. Five additional FCD‐BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery.

Results: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel‐shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD‐BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery.

Conclusion: Focal cortical dysplasias of Taylor's balloon‐cell type (FCD‐BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.
Standardization of Amygdalohippocampectomy with Intraoperative Magnetic Resonance Imaging: Preliminary Experience
Authors: Schwartz Theodore H. , Marks David , Pak Jayoung , Hill James , Mandelbaum David E. , Holodny Andrei I. , Schulder Michael
Published: March 2003

Summary:  Purpose: Intraoperative magnetic resonance imaging (IMRI) is an extremely useful neurosurgical tool in surgeries in which the extent of resection is known to have a significant impact on outcome. Residual hippocampus is the most common cause of recurrent seizures after temporal lobectomy for medial temporal lobe epilepsy. Although the risk/benefit ratio of a policy of universal radical hippocampal resection is not known, we hypothesized that IMRI would aid in the intraoperative assessment of the extent of hippocampal resection and assist in accomplishing a complete hippocampectomy.

Methods: Five consecutive patients with medically intractable medial temporal lobe epilepsy underwent a radical amygdalohippocampectomy as part of the their surgery for epilepsy. IMRI was used before surgery and after an initial resection. The quality of images was assessed. Postoperative MR images were evaluated by a radiologist to determine the extent of resection of the amygdala, hippocampus, and parahippocampal gyrus.

Results: There were no perioperative infections. After a mean follow‐up of 10 months, all patients are seizure free. T1‐weighted coronal intraoperative images were judged adequate at visualizing the medial structures in all patients. T2 and fluid‐attenuated inversion recovery (FLAIR) images did not provide useful information. Postoperative MR images indicated that a complete hippocampectomy had been achieved in all patients.

Conclusions: IMRI is a useful adjunct in the surgical treatment of medial temporal lobe epilepsy and perhaps the most reliable method of standardizing a complete hippocampectomy. T1‐weighted coronal images are the most helpful sequence.
Risk Factors for Suicide in Epilepsy: A Case Control Study
Authors: Nilsson Lena , Ahlbom Anders , Farahmand Bahman Y. , Åsberg Marie , Tomson Torbjörn
Published: March 2003

Summary:  Purpose: Suicide is considered to be one of the most important causes of death contributing to the increased mortality of persons with epilepsy. We investigated the association between the risk of suicide in persons with epilepsy and clinical factors that might increase or have been suggested to increase the risk of suicide.

Methods: A case–control study was nested within a cohort of 6,880 patients registered in the Stockholm County In‐Patient Register with a diagnosis of epilepsy. The study population was followed up through the National Cause of Death Register. Twenty‐six cases of suicide, 23 cases of suspected but not proven suicide, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data were collected through medical record review.

Results: There was a ninefold increase in risk of suicide with mental illness and a 10‐fold increase in relative risk (RR) with the use of antipsychotic drugs. The estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4–58.3] for onset of epilepsy at younger than 18 years, compared with onset after 29 years. The risk of suicide seemed to increase with high seizure frequency and antiepileptic drug (AED) polytherapy, although the estimates were imprecise and the associations not statistically significant. Insufficient data on seizure frequency and changes in AED dosage due to incomplete case records were associated with high RRs. We found no association between risk of suicide and any particular AED, with type of epilepsy, or localization or lateralization of epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1–1.7)].

Conclusions: The profile of the epilepsy patient who commits suicide that emerges from our study is a patient with early onset (particularly onset during adolescence) but not necessarily severe epilepsy, psychiatric illness, and perhaps inadequate neurologic follow‐up. Previous reports of an association with temporal lobe epilepsy could not be confirmed.
Serum S‐100 Protein Is Not a Suitable Seizure Marker in Temporal Lobe Epilepsy
Authors: Leutmezer Fritz , Wagner Oswald , Baumgartner Christoph
Published: March 2003

Summary:  Purpose: S‐100 protein is a sensitive marker of various brain diseases; however, its role in epilepsy is controversially discussed in the literature. We therefore studied the temporal profile of serial concentrations of S‐100 protein in serum after secondarily generalized tonic–clonic seizures during video‐EEG monitoring.

Methods: Ten patients with mesial temporal lobe epilepsy were prospectively studied. Serum S‐100 protein was measured after a seizure‐free period of ≥24 h (baseline) and 30 min, 3, 6, 12, and 24 h after a secondarily generalized tonic–clonic seizure of temporal lobe origin in nine and a convulsive status epilepticus in one patient.

Results: All S‐100 levels were within the normal range, except for those of one patient at baseline. Mean values were 0.045 μg/L (range, 0.003–0.13 μg/L) at baseline, 0.038 μg/L (range, 0.003–0.09 μg/L) at 30 min, 0.036 μg/L (range, 0.003–0.08 μg/L) at 3 h, 0.034 μg/L (range, 0.003–0.07 μg/L) at 6 h, 0.034 μg/L (range, 0.003–0.08 μg/L) at 12 h, and 0.035 μg/L (range, 0.003–0.09 μg/L) at 24 h after seizure offset. There were no significant differences between mean concentrations at any interval postictally.

Conclusions: We could not detect any significant alterations in serum S‐100 protein concentration either after a single secondarily generalized tonic–clonic seizure or after convulsive status epilepticus in patients with temporal lobe epilepsy. Our data do not confirm previous work, which suggested serum S‐100 protein to be a suitable marker for epileptic seizures.
Systematic Review and Meta‐analysis of Incidence Studies of Epilepsy and Unprovoked Seizures
Authors: Kotsopoulos Irene A. W. , Van Merode Tiny , Kessels Fons G. H. , De Krom Marc C. T. F. M. , Knottnerus J. André
Published: March 2003

Summary:  Purpose: To evaluate the methodology of incidence studies of epilepsy and unprovoked seizures and to assess the value of their findings by summarizing their results.

Methods: A Medline literature search from January 1966 to December 1999 was conducted. In each selected study, key methodologic items such as case definition and study design were evaluated. Furthermore, a quantitative meta‐analysis of the incidence data was performed.

Results: Forty incidence studies met the inclusion criteria. There was considerable heterogeneity in study methodology, and the methodologic quality score was generally low. The median incidence rate of epilepsy and unprovoked seizures was 47.4 and 56 per 100,000, respectively. The age‐specific incidence of epilepsy was high in those aged 60 years or older, but was highest in childhood. Males had a slightly higher incidence of epilepsy (median, 50.7/100,000) than did females (median, 46.2/100,000), and partial seizures seemed to occur more often than generalized seizures. Developing countries had a higher incidence rate of epilepsy (median, 68.7/100,000) than did industrialized countries (median, 43.4/100,000). Similar results were found for unprovoked seizures. The incidence of epilepsy over time appears to decrease in children, whereas it increases in the elderly.

Conclusions: The age‐specific incidence of epilepsy showed a bimodal distribution with the highest peak in childhood. No definitive conclusions could be reached for the incidence of unprovoked seizures and other specific incidence rates of epilepsy. More incidence studies with an adequate study methodology are needed to explore geographic variations and time trends of the incidence of epilepsy and unprovoked seizures.
A Detailed Analysis of Symptomatic Posterior Cortex Seizure Semiology in Children Younger Than Seven Years
Authors: Fogarasi András , Boesebeck Frank , Tuxhorn Ingrid
Published: March 2003

Summary:  Purpose: To analyze the semiology of seizure onset and evolution in young children with posterior cortex epilepsy (PCE), compare this with adult reports, and assess age‐related differences.

Methods: We videotaped and analyzed 110 seizures from 18 patients with PCE, aged 3–81 months. All had a good prognosis after posterior epileptogenic zone removal. Ictal events were categorized by behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included myoclonic, tonic, clonic, unclassified motor seizures, and epileptic spasm. A time‐scaled data sheet was developed to record each epileptic event as onset, very early, early, or late manifestation.

Results: Patients had a high seizure frequency with ≤100 attacks/day; one third of them showed a cluster tendency. The mean duration of seizures was 67 s. The most common seizure components were motor manifestations (with myoclonic and tonic seizures), but psychomotor (automotor), hypomotor attacks, and isolated auras also were frequently observed. Clinical seizure spread was frequent; auras and visual sensory signs were difficult to record in this age. Typical phenomena during seizures included behavioral changes, ictal vocalization, smile, flush, head nod, oculomotor features, and late‐appearing oral automatisms, whereas hypermotor and secondarily generalized tonic–clonic seizures were not seen.

Conclusions: Our results suggest that PCE in infants and young children is very heterogeneous but shows important age‐related features. Compared with adults, children with PCE have shorter but more frequent seizures; they rarely report aura or visual sensory signs, only sporadically develop hypermotor and secondarily generalized tonic–clonic seizures, whereas ictal smile, flush, head nod, and behavioral change are typical features at this age. Because of frequent subtle ictal phenomena, long‐term video‐EEG monitoring is a useful diagnostic tool with infants and young children with PCE.
Widespread Upregulation of Drug‐resistance Proteins in Fatal Human Status Epilepticus
Authors: Sisodiya Sanjay M. , Thom Maria
Published: March 2003

Summary:  Purpose: Accumulating evidence implicates drug‐transporter proteins ABCB1 and ABCC1 in resistance to multiple antiepileptic drugs (AEDs) in refractory epilepsy. These proteins are upregulated in surgically resected human brain tissue containing epileptogenic pathologies, including cortical dysplasia. In surgically resected cases, no upregulation is seen in normal adjacent tissue, suggesting that neither seizures nor prolonged exposure to AEDs need induce ABCB1 or ABCC1 expression. We wished to determine if status epilepticus might cause upregulation of these proteins.

Methods: Immunohistochemistry was performed for ABCB1 and ABCC1 in postmortem human brain tissue from a patient who died in status epilepticus and was found to have unihemispheric cortical dysplasia.

Results: There was upregulation of both proteins, as expected, in the hemisphere containing dysplasia. There also was widespread upregulation of both proteins in glia from the normal hemisphere. Previous work shows that drug treatment does not cause such upregulation.

Conclusions: Upregulation of these proteins in histologically normal brain tissue is most likely the result of seizures in status, as seen in animal models. The findings provide a possible explanation for the appearance of AED resistance in prolonged status and emphasise the importance of prompt treatment of status epilepticus.
Video‐EEG Monitoring in Adults
Authors: Cascino Gregory D.
Published: March 2003

Summary: The routine EEG study may prove inadequate in selected patients with recurrent and unprovoked seizures. Video‐EEG monitoring is an important diagnostic innovation that may be used to confirm the diagnosis of a seizure disorder and classify seizure type. The methodologies and clinical applications of video‐EEG monitoring are reviewed. Long‐term EEG recordings may be performed as an outpatient or in an epilepsy monitoring unit. Potential techniques for video‐EEG monitoring include prolonged conventional routine EEG, ambulatory EEG, and computer‐assisted EEG recordings. Periictal SPECT studies performed during long‐term EEG recordings in the epilepsy monitoring unit may increase the diagnostic yield of a presurgical evaluation. Video‐EEG monitoring is essential for surgical localization in patients with intractable partial epilepsy being considered for a focal cortical resection. The studies may also be necessary to confirm the presence of nonepileptical clinical episodes.
Epilepsy Surgery in Childhood
Authors: Cross J. Helen
Published: March 2003

Summary: Epilepsy surgery in childhood can now be more readily considered as a result of enhanced presurgical investigative techniques and safer neurosurgical practice. As in adults, surgery available may be resective (focal resection or hemispherectomy) or functional. The most common procedures are temporal lobectomy and hemispherectomy, with malformative lesions and developmental tumours the next common pathology. The timing of surgery requires careful consideration, and the definition of drug resistance given specific thought in the young child. Presurgical evaluation should be noninvasive where possible, and should include optimised MRI, including 3D data set and video EEG telemetry to document seizures. Detection of temporal lobe abnormalities in temporal lobe epilepsy with MR may be enhanced using quantitative and semiquantitative techniques. Ictal and interictal SPECT may be useful in providing information about the seizure onset zone, if reviewed in conjunction with MR data and video‐EEG. Interictal PET is more likely to demonstrate abnormalities relating to structural defects, but may be particularly useful in infants where incomplete myelination may restrict structural information provided by MRI. Neuropsychology testing plays a major role by the determination of verbal and nonverbal function in older children, and in the determination of cerebral dominance. Functional MRI for determination of language or motor cortex may enhance such evaluation, although it is limited to older unsedated children at present. Although the aims of the presurgical evaluation remain similar to adult practice, the range of children presenting is wide, and the aims and likely outcome of surgery require careful evaluation with the family. This aside, the benefits of seizure elimination or reduction in drug‐resistant focal epilepsy prior to adolescence, as well as in certain early catastrophic epilepsies of childhood, remain self apparent.
The Economic Cost of Epilepsy: A Review of the Literature
Authors: Begley Charles E. , Beghi Ettore
Published: March 2003

Summary: Economic concerns are increasingly important in health system design, provider payment, and research funding decisions. Cost estimates are needed to provide insight into where the potential opportunities for cost‐savings lie and to lay the groundwork for research to determine how to treat the disorder more effectively. The methods used by economists to estimate the direct and indirect costs of epilepsy are reviewed and results from studies in different countries are discussed. General patterns across patients with different types of conditions are reported. Gaps in the literature are identified and future research needs are assessed.
The Genetic Absence Epilepsy Rat from Strasbourg (GAERS), a Rat Model of Absence Epilepsy: Computer Modeling and Differential Gene Expression
Authors: Lakaye Bernard , Thomas Elisabeth , Minet Arlette , Grisar Thierry
Published: March 2003

Summary:  Purpose: We present results obtained by computer modeling of the thalamic network and differential gene expression analysis in a rat strain with absence epilepsy, the genetic absence epilepsy rat from Strasbourg (GAERS).

Methods: (a) Computer modeling used equations from the Hodgking–Huxley model with a circuit of 13 reticular thalamic (nRt) and 39 thalamocortical (TC) neurons; (b) gene‐expression analysis using differential mRNA display (DD), in situ hybridization, Northern blotting, and competitive reverse transcriptase–polymerase chain reaction (RT‐PCR).

Results: (a) Computer modeling showed an increased network synchrony in the thalamic circuit as the value of conductance of low‐voltage activated calcium channel (LVACC) is increased. (b) Using differential mRNA display, a 40% upregulation of the H‐ferritin mRNA in the hippocampus was demonstrated. Looking for some candidate genes of the VACC family, no difference was found in the α1G mRNA expression between GAERS and control animals, whereas a decreased expression of the α1E subunit was observed in the cerebellum and the brainstem of the GAERS. This phenomenon was not observed in young animals when the epileptic phenotype is not expressed.

Conclusions: The use of computer modeling appeared to be an efficient way to evaluate the impacts of electrophysiologic findings in vivo from single cells on an entire circuit. No clear single gene defect was revealed so far in GAERS. More information could arise from linkage analysis. However, some brain structures like hippocampus or cerebellum classically not known to be involved in the production of absence spike‐and‐wave discharges could in fact participate in the development of this phenotype.
Interaction of Excitatory Amino Acid Agonists with Cortical Afterdischarges in Developing Rats
Authors: Mareš P. , Haugvicová R. , Kubová H.
Published: March 2003

Summary:  Purpose: To determine the role of excitatory amino acids (EAAs) in genesis of two types of epileptic afterdischarges.

Methods: Cortical stimulation and recording electrodes were implanted in 12‐, 18‐, and 25‐day‐old rats. Epileptic afterdischarges were induced by rhythmic stimulation of sensorimotor cortex. The stimulation was repeated 6 times with 20‐min intervals. Ten minutes after the first afterdischarge, N‐methyl‐d‐aspartate, homocysteine, or kainic acid was injected. The doses were chosen individually for different age groups to be subconvulsive. Type and duration of afterdischarges as well as type and severity of motor correlates were evaluated.

Results: N
‐methyl‐
d
‐aspartate prolonged afterdischarges only in 12‐day‐old rats, whereas two other drugs did it in all age groups. Motor correlates of afterdischarges were changed to flexion seizures in 12‐day‐old rats after
N
‐methyl‐
d ‐aspartate and homocysteine; in 25‐day‐old rats homocysteine led to generalized tonic–clonic seizures (i.e., both patterns seen after substantially higher doses of these drugs in nonstimulated rats). Seizures lasted tens of minutes. Kainic acid did not change the motor pattern in any age group, but nonconvulsive EEG seizures were recorded in the interstimulation periods mainly in 18‐ and 25‐day‐old rats. Increased transition into the limbic type of afterdischarges appeared only after homocysteine in 18‐ and 25‐day‐old rats.

Conclusions: A mutual potentiation of epileptic phenomena was induced by two agents. The actions of N‐methyl‐d‐aspartate and kainic acid differ in all age groups; the effects of homocysteine were identical with those of N‐methyl‐d‐aspartate in 12‐day‐old rats but not later. Only homocysteine augmented transition into the limbic type of afterdischarges.
Evidence That ATP Participates in the Pathophysiology of Pilocarpine‐Induced Temporal Lobe Epilepsy: A Fluorimetric, Immunohistochemical, and Western Blot Studies
Authors: Vianna E. P. M. , Ferreira A. T. , Naffah‐Mazzacoratti M. G. , Sanabria E. R. G. , Funke M. , Cavalheiro E. A. , Fernandes M. J. S.
Published: March 2003

Summary:  Purpose: This study was performed to study the role of adenosine triphosphate (ATP) in the brain of pilocarpine‐induced chronic epileptic rats.

Methods: ATP‐mediated changes in intracellular calcium were studied by the fura‐2 method. Immunohistochemistry and Western blotting methods were used to localize and quantify P2X7 receptors in these animals.

Results: The fluorimetric study in chronic rats revealed a biphasic response indicating the presence of P2X7 receptors. The Western blotting study showed an increase of 80% of P2X7 expression in chronic rats compared with the control group. P2X7 immunoreactivity resembled mossy fiber sprouting at the dentate gyrus of epileptic animals.

Conclusions: These results suggest that purinergic receptors may participate in the pathophysiology of temporal lobe epilepsy.
Dynamic Changes of Status Epilepticus‐Induced Neuronal Degeneration in the Mediodorsal Nucleus of the Thalamus During Postnatal Development of the Rat
Authors: Kubová H. , Druga R. , Haugvicová R. , Suchomelová L. , Pitkanen A.
Published: March 2003

Summary:  Purpose: Status epilepticus (SE) was previously found to induce damage in the mediodorsal nucleus of the thalamus (MD) in both adult and immature rats. This study was designed to describe age‐related changes of SE‐induced neuronal degeneration in this part of the brain.

Methods: SE was induced by LiCl/pilocarpine in five age groups of rats (P12–P25). Distribution of degenerating neurons was studied at various time intervals from 4 h up to 1 week using Fluoro Jade B (FJB) staining. For P12 and P25 rats, an interval of 3 months was added.

Results: Damaged neurons were found in all age groups during a 1‐week period after SE. Patterns of neuronal degeneration, however, changed in an age‐related manner. In animals at P12 and P15, FJB‐labeled neurons were located in the central and lateral segment of the MD. In the P18 group, degenerating neurons occurred in all three segments of the MD, with a prevalence in central and lateral subdivisions. In contrast, in P21 and P25 rats, FJB‐labeled neurons were predominantly located in the central and medial segments. Degenerating neurons were still present 3 months after SE in the medial segment in P25 animals, whereas no labeled neurons were detected in the P12 group at this time.

Conclusions: Our data demonstrate that the pattern of neuronal degeneration in MD is mainly related to age at SE onset. In addition to damage occurring during the acute phase of SE, a population of degenerating neurons was detected in P25 animals during the chronic period 3 months after SE.
The Contribution of J. H. Jackson to Present‐Day Epileptology
Authors: Sengoku Akira
Published: March 2003

Summary:Contributions made by John Hughlings Jackson (1835–1911) to today's epileptology are unparalleled, and what he did has still not been reevaluated. We divide his contributions into three themes: (a) He began his research with the seizures later named jacksonian seizures. Through his research, Jackson established a revolutionary definition quite similar to our contemporary definition of epilepsy. The first step was made to the neurosurgical treatment for epilepsy through his research. (b) He elucidated the mechanism of postepileptic psychosis by his theory of evolution–dissolution and positive–negative symptoms, later called jacksonism. (c) His encounter with his patient, Dr. Z, helped him to establish his idea of dreamy state, eventually leading to the concept of temporal lobe epilepsy.
Eustachian Valve Thrombus:
Authors: Onwuanyi Anekwe E. , Brown Robert J. , Vahedi Marjan , Narayanan Rajnikanth , Nash Ira S. , Goldman Martin E.
Published: March 2003

This case report describes a patient with pulmonary embolism (PE) in whom transesophageal echocardiography showed a thrombus in the right atrium attached to the eustachian valve (EV). The EV is typically absent in the adult, but when present it is considered to be benign. It is an uncommon site for thrombus formation. This patient was treated with systemic anticoagulation. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Helicobacter pylori und nichtsteroidale Antirheumatika
Authors: Knoflach P.
Published: March 2003

Beobachtungen über die Wechselwirkungen zwischen den beiden wesentlichen Ursachen von gastroduodenalen Läsionen – Einnahme von nichtsteroidalen Antirheumatika (NSAR) und Infektion mit Helicobacter pylori (H.p.) – sind zum Teil noch kontroversiell. Dabei muss die H. p.‐Infektion nicht unbedingt einen additiv oder synergistisch schädigenden Effekt entfalten, sondern kann möglicherweise auch protektiv gegenüber der NSAR‐Wirkung auf die Schleimhaut sein. Daraus leiten sich spezifische therapeutische Strategien für verschiedene klinische Situationen ab.
Cerebrospinal‐Fluid Lactate in Adult Mitochondriopathy with and without Encephalopathy
Authors: Finsterer J.
Published: March 2003

Summary: Despite improved diagnostic facilities, the diagnosis of mitochondriopathy (MCP) is sometimes difficult to establish. This study aimed to investigate whether CSF lactate can be of diagnostic help in this respect. Cerebrospinal‐fluid (CSF) lactate and its relation to resting lactate and lactate stress testing were investigated in 26 MCP patients, aged 30 – 84 years. The upper reference limit of CSF lactate, obtained from 28 healthy subjects, was 1.6 mmol/l. Seven MCP patients (27 %) had elevated CSF lactate. Five of these patients had central nervous system (CNS) abnormalities other than elevated CSF lactate. In two patients with increased cerebrospinal‐fluid lactate, lactate stress testing was normal or could not be carried out. In conclusion, CSF lactate is elevated in one quarter of adult MCP patients. CSF lactate is preferentially elevated in patients with additional CNS abnormalities other than elevated CSF lactate. If the results for resting lactate or lactate stress testing are normal or unavailable, determination of CSF lactate may be of diagnostic support in single cases.
Immature Teratoma in Both Mediastinum and Liver of a 21‐Year‐old Female Patient
Authors: Çöl C.
Published: March 2003

Summary: We present a case of an immature teratoma of the liver and the mediastinum. A 21‐year‐old female patient presented with dyspnea, abdominal pain, and abdominal mass. Abdominal ultrasonography showed a liver tumor which is located in the right lobe and composed of cystic and solid elements. Computed tomography (CT) also showed a big mass which contained multiple high density, nodular, semi‐solid, heterogenic structures in the liver and another mass which contained multiple low density cystic lesions in the anterior mediastinum. Right thoraco‐abdominal approach was performed on the patient and a complete macroscopic resection of tumors was achieved without complications. Both tumours were evaluated as having an intact capsule. The mediastinal tumour extended to the diaphragm on the right side, and is dissected from the ‘surrounding lung, pericardium’ and excised from diaphragm. Right hepatic lobectomy was performed for liver tumour. Intraoperative frozen sections of the liver tumor revealed teratoma. But the final pathological diagnosis was immature teratoma. Chemotherapy was given after surgery. The patient tolerated the procedure well and her postoperative course was unremarkable. At the first follow up 4 months after surgery she was alive and well and there was no evidence of recurrence, but the patient died within seven months with hepatic recurrence and spreading metastasis.
Behavioral phenotyping enhanced – beyond (environmental) standardization
Authors: Würbel H.
Published: March 2003

It is basic biology that the phenotype of an animal is the product of a complex and dynamic interplay between nature (genotype) and nurture (environment). It is far less clear, however, how this might translate into experimental design and the interpretation of animal experiments. Animal experiments are a compromise between modelling real world phenomena with maximal validity (complexity) and designing practicable research projects (abstraction). Textbooks on laboratory animal science generally favour abstraction over complexity. Depending on the area of research, however, abstraction can seriously compromise information gain, with respect to the real world phenomena an experiment is designed to model. Behavioral phenotyping of mouse mutants often deals with particularly complex manifestations of life, such as learning, memory or anxiety, that are strongly modulated by environmental factors. A growing body of evidence indicates that current approaches to behavioral phenotyping might often produce results that are idiosyncratic to the study in which they were obtained, because the interactive nature of genotype‐environment relationships underlying behavioral phenotypes was not taken into account. This paper argues that systematic variation of genetic and environmental backgrounds, instead of excessive standardization, is needed to control the robustness of the results and to detect biologically relevant interactions between the mutation and the genetic and environmental background of the animals.
The fallacy of behavioral phenotyping without standardisation
Authors: Van Der Staay F. J. , Steckler T.
Published: March 2003

Behavioral phenotyping of mutant mice is a new and challenging task for the behavioral neuroscientist. Therefore, standardisation of the experimental conditions is required to permit comparisons between the results of experiments within and between laboratories. Once mutation‐induced behavioral changes have been identified, phenotyping of mouse mutants should be performed along a systematic trajectory, which allows for an in‐depth characterisation of the mutant under investigation.
Adhesively bonded joints under cyclic loading spectra
Authors: Jones R. , Kotousov A. , Marshall I. H.
Published: March 2003

Abstract Current designs which involve the use of composite materials in primary aircraft structures are often conservative. This, in turn, significantly lowers the weight advantage that composites have over established metallic airframe materials. Strain restrictions are often applied because the failure mechanism(s) in (fibre) composite joints and stiffener runouts where the stress state is often complex, are not fully understood. Nevertheless, from the airworthiness perspective it is essential that both the static strength and the fatigue behaviour of the components subjected to complex multiaxial stress conditions are both understood and predicted. This topic is extremely complex, and numerous criteria ranging from the purely empirical to the theoretical have been proposed. In both cases, it is necessary to know the localised stress–strain history.

One common design methodology is to keep the stresses so low that fatigue will not be an issue. However, this can lead to an overly conservative design. On the other hand, while a detailed (nonlinear) finite element analysis can be performed it is often both resource‐intensive and time‐consuming. The present paper shows that Glinka's hypothesis can be used in order to calculate the localised stresses and strains for a bonded joint subjected to cyclic loading.

This is a new result and has not previously been noted. It has the potential to extend the Hart‐Smith design methodology to the adhesively bonded joints in order to encompass durability considerations. This formulation also raises the possibility of enabling the degree of conservatism inherent in traditional joint design to be relaxed provided that failure occurs in the adhesive.

This paper also addresses the problem of variable adhesive thickness. We show that while variable adhesive thickness can change the stress and the energy fields, the peak in the strain energy density is relatively insensitive to the stress–strain relationship for the adhesive and that Glinka's hypothesis still appears to be true. This means that, for the present class of problems, even if there is variability in the thickness of the adhesive bond the energy field and, hence, the strength of the joint can be estimated from a purely linear elastic analysis of the joint, provided that failure occurs in the adhesive.
Self‐similar crack patterns induced by spatial stress fluctuations
Authors: Dyskin A. V.
Published: March 2003

AbstractA mechanism of the formation of multiscale self‐similar crack structures in brittle materials is proposed based on the action of spatial random stress fluctuations (random stress fields) with vanishing mathematical expectation. The presence of self‐equilibrating stress fluctuations is, in many cases, characteristic of heterogeneous brittle materials even in the absence of external loading. Some examples are given by residual stresses—stresses caused by phase transformations or internal microscopic heat sources. If the stress fluctuations are strong enough to cause cracking, the cracks will be originated in regions with and perpendicular to the highest local tension. As a legacy of this special location, additional local tractions opening the crack in its centre are developed even in self‐equilibrating stress fields. This mechanism is modelled by disklike cracks opened by a pair of concentrated forces applied at the centre. Two cases are considered: (i) the crack growth in the moving equilibrium conditions caused by the self‐equilibrating stress fluctuations of increasing amplitude; and (ii) the subcritical crack growth under the stress fluctuations of either sustained (creep) or oscillating (fatigue) amplitudes. As the cracks grow, the interaction between them leads to a separation of crack sizes. The effects of the interaction are modelled by the differential self‐consistent method that is shown to become asymptotically accurate as the ratio between the sizes of the interacting cracks increases. The interaction results in the crack distribution tending to a self‐similar one with the distribution function proportional to the inverse fourth power of the crack radius.