bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of BRCT domains of BRCA1 and 53BP1: A biophysical analysis
Authors: Ekblad Caroline M.S. , Friedler Assaf , Veprintsev Dmitry , Weinberg Richard L. , Itzhaki Laura S. 
Published: February 2004

Abstract53BP1 interacts with the DNA‐binding core domain of the tumor suppressor p53 and enhances p53‐mediated transcriptional activation. The p53‐binding region of 53BP1 maps to the C‐terminal BRCT domains, which are homologous to those found in the breast cancer protein BRCA1 and in other proteins involved in DNA repair. Here we compare the thermodynamic behavior of the BRCT domains of 53BP1 and BRCA1 and examine their ability to interact with the p53 core domain. The free energies of unfolding are of similar magnitude, although slightly higher for 53BP1‐BRCT, and both populate an aggregation‐prone partly folded intermediate. Interaction studies performed in vitro by analytical size‐exclusion chromatography, analytical ultracentrifugation, and isothermal titration calorimetry reveal that 53BP1‐BRCT interacts with p53 with a Kd in the low micromolar range. Despite their homology with 53BP1‐BRCT domains, the BRCT domains of BRCA1 did not bind p53 with any detectable affinity. In summary, although other studies have indicated that the BRCT domains of both BRCA1 and 53BP1 interact with p53 core domain, the quantitative biophysical measurements performed here indicate that only 53BP1 can bind. Although both proteins may be involved in the same DNA repair pathways, our study indicates that a direct role in p53 function is unique to 53BP1.
Areas of Interictal Spiking Are Associated with Metabolic Dysfunction in MRI‐negative Temporal Lobe Epilepsy
Authors: Shih Jerry J. , Weisend Michael P. , Lewine Jeffrey , Sanders John , Dermon Jamie , Lee Roland 
Published: February 2004

Summary:  Purpose: The objective of our study was to determine noninvasively whether metabolic dysfunction is present in focal areas of interictal electrophysiologic abnormality and whether metabolic dysfunction correlates with frequency of spiking. Methods: We used a prospective, power analysis–driven, age‐matched design to study 20 subjects with nonlesional temporal lobe epilepsy by using magnetoencephalography (MEG) and proton magnetic resonance spectroscopy (1H‐MRS). MEG was used to localize the source area of interictal spikes. 1H‐MRS measured integrated peak areas for N‐acetyl compounds (NAA) and choline‐containing compounds (Cho) in both hippocampi, the MEG spike zone, and the region contralateral to the MEG spike zone in all subjects. 1H‐MRS was performed in seven controls. Results: Fifteen of 20 subjects had a lower NAA/Cho ratio in the MEG spike zone compared with the contralateral homologous region. NAA/Cho was significantly decreased in the MEG spike zone (p < 0.01). NAA/Cho ratios were not significantly different between the hippocampus ipsilateral and contralateral to the spike activity, or from control hippocampi. NAA/Cho ratios did not correlate with spike frequency. Conclusions: Metabolic dysfunction is present in focal areas of interictal spiking in nonlesional temporal lobe epilepsy. These findings confirm that functional abnormalities can be detected in vivo in radiographically normal‐appearing cortex exhibiting abnormal excitability.
The Cognitive Outcome of Hemispherectomy in 71 Children
Authors: Pulsifer Margaret B. , Brandt Jason , Salorio Cynthia F. , Vining Eileen P. G. , Carson Benjamin S. , Freeman John M. 
Published: February 2004

Summary: Purpose:Long‐term neuropsychological outcome was studied in 71 patients who underwent hemispherectomy for severe and intractable seizures at The Johns Hopkins Hospital between 1968 and 1997 and who agreed to participate. Seizures were due to cortical dysplasias (n = 27), Rasmussen syndrome (n = 37), or vascular malformations or strokes (n = 7). Both presurgical and follow‐up results are available and reported for 53 patients.Methods:Patients and caretakers were interviewed, and patients were administered standard measures of intelligence, receptive and expressive language, visual‐motor skills, adaptive/developmental functioning, and behavior.Results:Mean age at surgery was 7.2 years. At follow‐up, on average 5.4 years after surgery, 65% are seizure free, 49% are medication free, and, of those responding, none rated quality of life as worse than before surgery. Mean IQ was in the 70s for Rasmussen and vascular patients and in the 30s for cortical dysplasia patients. Language and visual‐motor skills were consistent with IQ. For Rasmussen patients only, language was significantly more impaired for left than for right hemispherectomy, both before surgery and at follow‐up. Adaptive skills were mildly impaired, with greatest impairment in the physical domain. Cognitive measures typically changed little between surgery and follow‐up, with IQ change <15 points for 34 of 53 patients; of the remainder, 11 declined and eight improved. Behavior was free of major problems, but social interactions and activities were limited.Conclusions:The most significant predictor of cognitive skills at follow‐up was etiology, with dysplasia patients scoring lowest in intelligence and language but not in visual‐motor skills. Regardless of etiology, most patients showed only moderate change in cognitive performance at follow‐up.
Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of Medication
Authors: Vainionpää Leena K. , Mikkonen Kirsi , Rättyä Johanna , Knip Mikael , Pakarinen Arto J. , Myllylä Vilho V. , Isojärvi Jouko I.T. 
Published: February 2004

Summary:  Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty‐one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age‐matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow‐up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T4), 70.2; SD, 10.9 nM; and free thyroxine (FT4), 11.5; SD, 1.8 pM] or OXC (T4, 74.9; SD, 16.4 nM; and FT4, 11.3; SD, 1.8 pM) than in the control girls (T4, 96.6; SD, 15.1 nM, and FT4, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty‐three% of the girls taking CBZ and 67% of the girls taking OXC had serum T4 and/or FT4 levels below the lower limit of the reference range. The VPA‐treated girls with epilepsy had normal serum T4 and FT4 concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication.
Seizure Semiology in the Elderly: A Video Analysis
Authors: Kellinghaus Christoph , Loddenkemper Tobias , Dinner Dudley S. , Lachhwani Deepak , O. Lüders Hans 
Published: February 2004

Summary:  Purpose: To describe the seizure semiology of patients older than 60 years and to compare it with that of a control group of younger adults matched according to the epilepsy diagnosis. Methods: Available videotapes of all patients aged 60 years and older who underwent long‐term video‐EEG evaluation at the Cleveland Clinic Foundation (CCF) between January 1994 and March 2002 were analyzed by two observers blinded to the clinical data. A younger adult control group was matched according to the epilepsy diagnosis, and their seizures also were analyzed. Results: Fifty‐four (3.3%) of the 1,633 patients were 60 years or older at the time of admission. For 21 of them, at least one epileptic seizure was recorded. Nineteen patients had focal epilepsy (nine temporal lobe, two frontal lobe, two parietal lobe, eight nonlocalized), and two patients had generalized epilepsy. Seventy‐three seizures of the elderly patients and 85 seizures of the 21 control patients were analyzed. In nine elderly patients and 14 control patients, at least one of their seizures started with an aura. Eleven elderly patients and 19 control patients lost responsiveness during their seizures. Approximately two thirds of the patients in both groups had automatisms during the seizures. Both focal and generalized motor seizures (e.g., clonic or tonic seizures) were seen less frequently in the elderly. Conclusions: Only a small percentage of the patients admitted to a tertiary epilepsy referral center for long‐term video‐EEG monitoring are older than 60 years. All seizure types observed in the elderly also were seen in the younger control group, and vice versa. Simple motor seizures were seen less frequently in the elderly.
Interaction between Anticonvulsants and Human Placental Carnitine Transporter
Authors: Wu Shu‐Pei , Shyu Ming‐Kwang , Liou Horng‐Huei , Gau Churn‐Shiouh , Lin Chun‐Jung 
Published: February 2004

Summary:  Purpose: To examine the inhibitory effect of anticonvulsants (AEDs) on carnitine transport by the human placental carnitine transporter. Methods: Uptake of radiolabeled carnitine by human placental brush‐border membrane vesicles was measured in the absence and presence of tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), valproic acid (VPA), and phenytoin (PHT). The mechanism of the inhibitory action of TGB was determined. Results: Most of the AEDs inhibited placental carnitine transport. Kinetic analyses showed that TGB had the greatest inhibitory effect [50% inhibitory concentration (IC50, 190 μM)], and the order of inhibitory potency was TGB > PHT > GBP > VPA > VGB, TPM > LTG. Further studies showed that TGB competitively inhibited carnitine uptake by the human placental carnitine transporter, suggesting that it may be a substrate for this carrier. Conclusions: Although the involvement of carnitine deficiency in fetal anticonvulsant syndrome requires further evaluation, potential interference with placental carnitine transport by several AEDs was demonstrated. Despite the higher inhibitory potency of TGB, given the therapeutic unbound concentrations, the results for VPA and PHT are probably more clinically significant.
Long‐term Cognitive Outcomes of a Cohort of Children with Cryptogenic Infantile Spasms Treated with High‐dose Adrenocorticotropic Hormone
Authors: Kivity Sara , Lerman Pinchas , Ariel Raya , Danziger Yardena , Mimouni Marc , Shinnar Shlomo 
Published: February 2004

Summary:  Purpose: To evaluate the outcome of children with cryptogenic infantile spasms treated with high‐dose synthetic adrenocorticotropic hormone (ACTH) and the relation between early treatment, within 1 month of onset, and outcome. Methods: We assessed the long‐term cognitive and seizure outcomes of 37 patients with cryptogenic infantile spasms (onset, age 3 to 9 months) receiving standardized treatment regimen of high‐dose tetracosactide depot, 1 mg IM every 48 h for 2 weeks, with a subsequent 8‐ to 10‐week slow taper and followed by oral prednisone, 10 mg/day for a month, with a subsequent slow taper for 5 months or until the infant reached the age of 1 year, whichever came later. Development was assessed before treatment. Seizure outcomes were followed up prospectively. Cognitive outcomes were determined after 6 to 21 years and analyzed in relation to treatment lag and pretreatment regression. Results: Twenty‐two infants were treated within 1 month of onset of infantile spasms, and 15 after 1 to 6.5 months. Normal cognitive outcome was found in all 22 (100%) patients of the early‐treatment group, and in 40% of the late‐treatment group. Normal cognitive outcome was found in all 25 (100%) patients who had no or only mild mental deterioration at presentation, including four in the late‐treatment group but in only three of the 12 patients who had had marked or severe deterioration before treatment. Conclusions: Early treatment of cryptogenic infantile spasms with a high‐dose ACTH protocol is associated with favorable long‐term cognitive outcomes. Once major developmental regression lasts for a month or more, the prognosis for normal cognitive outcome is poor. Further studies are needed on the optimal treatment regimen for this disorder.
Epilepsy Surgery for Pathologically Proven Hippocampal Sclerosis Provides Long‐term Seizure Control and Improved Quality of Life
Authors: Lowe Adrian J. , David Efraim , Kilpatrick Christine J. , Matkovic Zelko , Cook Mark J. , Kaye Andrew , O'Brien Terence J. 
Published: February 2004

Summary:  Purpose: To examine long‐term seizure and quality‐of‐life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow‐up (generally <2 years) and has grouped patients across multiple pathologies. Methods: Fifty consecutive patients were identified as having had a temporal lobectomy for the treatment of temporal lobe epilepsy at Royal Melbourne Hospital with pathologically proven HS and ≥2 years' follow‐up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE‐89), and antiepileptic drug (AED) use. The mean follow‐up was 5.8 years (range, 2–9.2). Results: The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =–234, p < 0.01). Seizure recurrence was associated with a reduction in AED intake or absorption in five (29%) of 17 cases, including three of the five patients with a first seizure recurrence after 24 months after surgery. Conclusions: Temporal lobectomy provides continued long‐term seizure control in the majority of patients with HS. However, patients remain at risk of seizure recurrence ≥2 years after surgery. Long‐term quality of life is dependent on seizure outcome.
Evidence for Linkage between Juvenile Myoclonic Epilepsy–Related Idiopathic Generalized Epilepsy and 6p11‐12 in Dutch Families
Authors: Pinto Dalila , De Haan Gerrit‐Jan , Janssen Guus A. M. A. J. , Boezeman Eduard H. , Van Erp M. Gerard , Westland Birgit , Witte Jorine , Bader Adri , Halley Dicky J. J. , Kasteleijn‐Nolst Trenité Dorothée G. A. , Lindhout Dick , Koeleman Bobby P. C. 
Published: February 2004

Summary:  Purpose: Previous linkage studies provided evidence for juvenile myoclonic epilepsy (JME) susceptibility loci at 6p11‐12, HLA‐6p21.3 region, 15q14, and 5q34. These results indicate locus heterogeneity or interpopulation differences, thus underlining the importance of replication studies. Methods: We describe a replication linkage study of the 6p‐q13 region in 18 families ascertained from JME probands of Dutch descent. In the presence of heterogeneity, the definition of the disease status may be crucial, and we therefore used two disease phenotypes: narrow [JME/idiopathic generalized epilepsy (IGE)‐“only”] and broad (JME/IGE‐plus‐fast EEG background activity). Results: We found evidence of linkage at 6p11‐12 in multipoint analyses (p < 0.01 in a replication study) for both these disease definitions. Analysis of this region, assuming heterogeneity and autosomal dominant inheritance with a conservative 60% of penetrance, gave a maximum multipoint parametric lod score of 2.07 at D6S1573 for the narrow phenotype and peaked at 2.53 between D6S1623 and D6S1573 for the broad phenotype. The p value for nonparametric linkage reached 0.0013 for the narrow phenotype and 0.0010 for the broad. Significant exclusion (lod score ≤2) was found for the HLA region and for 10 to 30 cM telomeric to HLA. Our results provide evidence for a susceptibility locus for JME/IGE‐plus‐fast EEG background activity at 6p11‐12. Conclusions: Additionally, by using a narrow definition, we were able to confirm previous evidence for a JME–IGE locus at this location.
Specific Epileptic Syndromes Are Rare Even in Tertiary Epilepsy Centers: A Patient‐oriented Approach to Epilepsy Classification
Authors: Kellinghaus Christoph , Loddenkemper Tobias , Najm Imad M. , Wyllie Elaine , Lineweaver Tara , Nair Dileep R. , Lüders Hans O. 
Published: February 2004

Summary:  Purpose: To assess the practicability and reliability of a five‐dimensional patient‐oriented epilepsy classification and to compare it with the International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The dimensions consist of the epileptogenic zone, semiologic seizure type(s), etiology, related medical conditions, and seizure frequency. Methods: The 185 epilepsy patients (94 adults, 91 children, aged 18 years or younger) were randomly selected from the database of a tertiary epilepsy center and the general neurological department of a metropolitan hospital (28 adults). The charts were reviewed independently by two investigators and classified according to both the ILAE and the patient‐oriented classification. Interrater reliability was assessed, and a final consensus among all investigators was established. Results: Only four (4%) adults and 19 (21%) children were diagnosed with a specific epilepsy syndrome of the ILAE classification. All other patients were in unspecific categories. The patient‐oriented classification revealed that 64 adults and 56 children had focal epilepsy. In an additional 34 adults and 45 children, the epileptogenic zone could be localized to a certain brain region, and in 14 adults and five children, the epileptogenic zone could be lateralized. Fourteen adults and 21 children had generalized epilepsy. In 16 adults and 14 children, it remained unclear whether the epilepsy was focal or generalized. Generalized simple motor seizures were found in 66 adults and 52 children, representing the most frequent seizure type. Etiology could be determined in 40 adults and 45 children. Hippocampal sclerosis was the most frequent etiology in adults (10%), and cortical dysplasia (9%), in children. Seven adults and 31 children had at least daily seizures. Seventeen adults and 26 children had rare or no seizures at their last documented contact. The most frequent related medical conditions were psychiatric disorders and mental retardation. Interrater agreement was high (kappa values of 0.8 to 0.9) for both the patient‐oriented and the ILAE classification. Conclusions: Specific epilepsy syndromes included in the current ILAE classification are rare even in a tertiary epilepsy center. Most patients are included in unspecific categories that provide only incomplete information. In contrast, all of the patients could be classified by the five‐dimensional patient‐oriented classification, providing all essential information for the management of the patients with a high degree of interrater reliability.
Benign Focal Epileptiform Discharges of Childhood and Hippocampal Sclerosis
Authors: Pan Andrew , Gupta Ajay , Wyllie Elaine , Lüders Hans , Bingaman William 
Published: February 2004

Summary:  Purpose: Benign focal epileptiform discharges of childhood (BFEDCs) are common EEG findings between ages 4 and 14 years. This epoch of maturational development overlaps with the age at presentation of temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) in children. Methods: From our series of 17 preadolescent children who eventually underwent anteromesial temporal resection for medically refractory TLE due to HS, we identified two children, plus one thereafter, who were initially dismissed as candidates for epilepsy surgery because of abundant extratemporal sharp waves, which were bilateral in two cases. The sharp waves had the distinctive morphology, distribution, and sleep activation suggestive of BFEDCs, but the medical intractability and seizure symptoms were unusual for benign focal epilepsy of childhood. Results: In each case, surgical candidacy was clarified when magnetic resonance imaging (MRI) showed unilateral HS and video‐EEG demonstrated seizure onset in the ipsilateral anteromesial temporal region. The postoperative freedom from seizures in each case (follow‐up, 2 to 4 years) confirmed that HS was the primary epileptogenic process, and that the BFEDCs were incidental or an atypical secondary manifestation. Conclusions: These cases illustrate the need for more extensive study of children with BFEDCs when medical intractability and seizure symptoms speak against a simple diagnosis of benign focal epilepsy of childhood. In addition, we observed that the BFEDCs in two of our children had an unusual bilateral occipitofrontal distribution, and we speculate that the coexistence of the BFEDCs in children with HS may not be an incidental finding.
Telephone‐induced Seizures: A New Type of Reflex Epilepsy
Authors: Michelucci Roberto , Gardella Elena , De Haan Gerrit‐Jan , Bisulli Francesca , Zaniboni Anna , Cantalupo Gaetano , Alberto Tassinari Carlo , Tinuper Paolo , Nobile Carlo , Nichelli Paolo , Kasteleijn‐Nolst Trenité Dorothée G. A. 
Published: February 2004

Summary: Purpose:To report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone.Methods:Three patients with a history of telephone‐induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video‐EEG monitoring to record the reflex seizures also was performed in all cases.Results:The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient, a telephone‐induced seizure arising from the dominant temporal lobe was recorded by means of video‐EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans.Conclusions:We suggest that telephone epilepsy is a previously unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.