bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of the Head‐Upright Tilt Test for Distinguishing Syncope and Epilepsy in Children
Authors: Eirís‐Puñal J. , Rodríguez‐Núñez A. , Fernández‐Martínez N. , Fuster M. , Castro‐Gago M. , Martinón J. M. 
Published: March 2003

Summary:  Purpose: Episodic loss of consciousness in children, whether or not associated with hypertonia or short‐duration clonic movements, presents a diagnostic challenge to the pediatrician and child neurologist. We provide some evidence of the usefulness of the head‐upright tilt test for investigating the causes of transient loss of consciousness in children, and for distinguishing between syncope, convulsive syncope, and epilepsy.Methods: We studied nine children previously diagnosed as epileptic on the basis of compatible clinical events and epileptiform findings in routine EEGs who were treated over the long term with antiepileptic drugs, but whose clinical records suggested syncope or convulsive syncope rather than epilepsy on reevaluation. All subjects underwent head‐upright tilt testing.Results: The tilt‐test result was positive in all nine cases, with the patients reporting the same symptoms as in the previously considered epileptic attacks.Conclusions: Inadequate histories and misuse/overinterpretation of EEG results often lead to misdiagnosis of epilepsy in children. The head‐upright tilt test is a useful and reliable diagnostic technique, allowing syncopal events to be induced and evaluated under controlled conditions. In a subset of patients, it may help to distinguish epilepsy from simple or convulsive syncope.
A Postmarketing Surveillance Study of Gabapentin as Add‐on Therapy for 3,100 Patients in England
Authors: Wilton Lynda V. , Shakir Saad 
Published: March 2003

Summary:  Purpose: Our aim was to monitor the use of gabapentin (GBP) by patients prescribed this drug by primary care physicians in England soon after it was marketed in the United Kingdom.Methods: A noninterventional observational cohort study was conducted by using the technique of prescription‐event monitoring. Patients were identified from dispensed National Health Service prescriptions. Outcome data were obtained from questionnaires sent to the doctor ∼6 months after the initial prescription. These data included demographic information, events reported since starting GBP, and reason for stopping the drug, if it was stopped. Incidence rates were calculated for given periods for all events reported. Additional information was requested for selected events of medical interest, including pregnancies. Standardised mortality ratio (SMR) was calculated.Results: The cohort comprised 3,100 patients, of whom 136 (4%) were children. The median duration of treatment was 8.1 months. The most frequently reported adverse events reported during the first month of treatment, drowsiness/sedation, dizziness, and malaise/lassitude, also were the commonest reasons for discontinuing GBP and reported as suspected adverse drug reactions (ADRs). There were no congenital anomalies in the 11 babies born to women who used GBP during the first trimester of pregnancy. Crude mortality rate was 5 times that in general population but similar to that in other published studies.Conclusions: Neurologic‐related events were the most frequently reported adverse events. They also were the commonest reasons for discontinuing treatment and reported as suspected ADRs. No previously unrecognised adverse events were detected in this large cohort of patients who were among the first treated with gabapentin in England.
Performance Reassessment of a Real‐time Seizure‐detection Algorithm on Long ECoG Series
Authors: Osorio Ivan , Frei Mark G. , Giftakis Jon , Peters Tom , Ingram Jeff , Turnbull Mary , Herzog Michele , Rise Mark T. , Schaffner Scott , Wennberg Richard A. , Walczak Thaddeus S. , Risinger Michael W. , Ajmone‐Marsan Cosimo 
Published: March 2003

Summary:  Purpose: Automated seizure detection and blockage requires highly sensitive and specific algorithms. This study reassessed the performance of an algorithm by using a more extensive database than that of a previous study and its suitability for safety/efficacy closed‐loop studies to block seizures in humans.Methods: Up to eight electrocorticography (EcoG) channels from 15 subjects were analyzed off‐line. Visual and computerized analyses of the data were performed by different (blinded) investigators. Independent visual analysis also was performed for clinical seizures and for detections identified only by the algorithm. The following were computed: FP rate, number of FNs, latency to automated detection, warning rate for clinical onset and warning times, seizure duration/intensity, and interrater agreement. Adaptations to improve performance were performed when indicated.Results: Fourteen subjects met inclusion criteria. Generic algorithm “relative sensitivity” for clinical seizures was 100%; two undetected subclinical seizures and two unclassified seizures were captured after adaptation. FPs/day were zero in seven and fewer than one in an additional three subjects. Adaptations for four subjects with greater than 1 FP/day (7.7–66.6/day) reduced the rate to 0 in one subject and to fewer than five FP/day (1.7–4.2/day) in the remainder. Generic latency to automated detection was <5 s in eight of 13 subjects, and in 12 of 13 after adaptation. Detections provided warning of clinical onset in three of four subjects in whom it always followed electrographic onset, and in four of four after adaptation. Interrater agreement was low for FPs and EDs.Conclusions: The generic algorithm demonstrated high sensitivity, specificity, and speed, characteristics further enhanced by adaptation. This algorithm is well suited for seizure detection/warning and use in safety/efficacy closed‐loop therapy studies.
Kidney Stones, Carbonic Anhydrase Inhibitors, and the Ketogenic Diet
Authors: Kossoff Eric H. , Pyzik Paula L. , Furth Susan L. , Hladky Heather D. , Freeman John M. , Vining Eileen P. G. 
Published: March 2003

Summary: Purpose:Because carbonic anhydrase inhibitors and the ketogenic diet are each known risk factors for kidney stones, simultaneous use of these therapies has been discouraged. The objective of this study was to establish the prevalence of nephrolithiasis in children in this combination‐therapy population.Methods:Since 1996, 301 children have been started on the ketogenic diet at our institution. A retrospective cohort study of renal calculi in ketogenic diet patients was performed to evaluate the increased risk with combined use of a carbonic anhydrase inhibitor.Results:In 15 (6.7%) of 221 children on the ketogenic diet without the use of carbonic anhydrase inhibitors, stones developed. In five (6.3%) of the 80 children on the diet in combination with topiramate or zonisamide, stones developed. There was no difference between these two groups (p = 0.82). No child was treated with either acetazolamide or more than one carbonic anhydrase inhibitor simultaneously. Prior ketogenic diet duration was shorter (10.4 vs. 22.4 months; p = 0.03), and more children had either a family history of renal stones or significant urologic abnormalities (80 vs. 27%; p = 0.04) in the combination‐therapy group.Conclusions:The combined use of carbonic anhydrase inhibitors and the ketogenic diet does not increase the risk of kidney stones. We recommend that all patients treated with combination therapy should be treated with increased hydration. Urine alkalinization should be considered for children with previous renal abnormalities, family histories of kidney stones, hematuria, or elevated urine calcium‐to‐creatinine ratios. If renal stones are found, we advocate discontinuation of the carbonic anhydrase inhibitor.
Risk of Extremity Fractures in Adult Outpatients with Epilepsy
Authors: Persson Hakan B. I. , Alberts K. A. , Farahmand B. Y. , Tomson T. 
Published: March 2003

Summary:  Purpose: To study the incidence of extremity fractures in a group of adult patients with epilepsy attending an outpatient clinic compared with the incidence of fractures in the general population in the same geographic area.Methods: We selected 177 consecutive adult patients with epilepsy attending the outpatient clinic at the Department of Neurology at Karolinska Hospital in Stockholm in 1995. This study population was matched with an Injury Registry to identify those epilepsy patients who during 1991 through 1995 attended the emergency department for an extremity fracture. The observed number of fractures in the epilepsy group was compared with the corresponding number of expected cases based on regional fracture rates. Relative‐risk estimates for fractures were calculated with respect to the duration of epilepsy, mono‐ or polytherapy, and history of tonic–clonic seizures.Results: Twenty (11%) of 177 patients sustained 23 fractures that prompted a visit to the emergency department. The incidence of fractures in the epilepsy patients was 23.8/1,000 person‐years. The overall Standardized Morbidity Ratio (SMR) was 2.39 (95% CI, 1.52–3.59). A significantly higher risk for fractures was thus found in patients with epilepsy. Risk factors were age 45 years or older, male sex, and occurrence of generalized seizures. It also was found that the relative risk of fractures was higher during the first and second year compared with ≥5 years after diagnosis (RR, 3.71; 95% CI, 1.20–11.48).Conclusions: Our results highlight the risk of fractures in outpatients with epilepsy. In this patient group, 43% of the fractures were definitely or possibly seizure related. Males 45 years or older are a particular risk group. Special attention is required for this group of patients who are at higher risk for fractures. The risk is apparently higher in the first 2 years after diagnosis, although potential bias in ascertainment of fracture incidents in our study may have underestimated the long‐term risk for fractures.
Predictive Value of Cortical Injury for the Development of Temporal Lobe Epilepsy in 21‐day‐old Rats: An MRI Approach Using the Lithium‐pilocarpine Model
Authors: Roch Catherine , Leroy Claire , Nehlig Astrid , Namer Izzie J. 
Published: March 2003

Summary: Purpose:Patients with temporal lobe epilepsy (TLE) usually had an initial precipitating injury in early childhood. However, epilepsy does not develop in all children who have undergone an early insult. As in patients, the consequences of the lithium‐pilocarpine‐induced status epilepticus (SE) are age dependent, and only a subset of 21‐day‐old rats will develop epilepsy. Thus with magnetic resonance imaging (MRI), we explored the differences in the evolution of lesions in these two populations of rats.Methods:SE was induced in 21‐day‐old rats by the injection of lithium and pilocarpine. T2‐weighted images and T2relaxation‐time measurements were used for detection of lesions from 6 h to 4 months after SE.Results:Three populations of rats could be distinguished. The first one had neither MRI anomalies nor modification of the T2relaxation time, and these rats did not develop epilepsy. In the second one, a hypersignal appeared at the level of the piriform and entorhinal cortices 24 h after SE (increase of 49% of the T2relaxation time in the piriform cortex) that began to disappear 48–72 h after SE; epilepsy developed in all these animals. The third population of rats showed a more moderate increase of the T2relaxation time in cortices (14% in the piriform cortex) that could not be seen on T2‐weighted images. Epilepsy developed in all these rats. Only in a subpopulation of the 21‐day‐old rats with epilepsy did hippocampal sclerosis develop.Conclusions:These results suggest that the injury of the piriform and entorhinal cortices during SE play a critical role for the installation of the epileptic networks and the development of epilepsy.
The Usefulness of Subtraction Ictal SPECT Coregistered to MRI in Single‐ and Dual‐headed SPECT Cameras in Partial Epilepsy
Authors: Kaiboriboon Kitti , Lowe Val J. , Chantarujikapong Sunanta I. , Hogan R. Edward 
Published: March 2003

Summary:  Purpose: To prove the clinical usefulness of SISCOM and compare SISCOM images derived from single‐ and dual‐headed single‐photon computed tomography (SPECT) cameras for localization of partial epileptic seizures.Methods: We retrospectively studied 38 partial epilepsy patients, using subtraction SPECT coregistered to magnetic resonance imaging (MRI; SISCOM). SPECT imaging of the first 15 patients was performed by single‐headed camera, and the next 23 patients by dual‐headed camera. Side‐by‐side ictal–interictal SPECT evaluation and SISCOM images were blindly reviewed and classified as either localizing to one of 16 sites or nonlocalizing. A third reviewer evaluated cases of disagreement between primary reviewers. Results were compared with seizure localization by any of the following three traditional techniques: surgical outcome, invasive, and noninvasive video‐EEG monitoring. The results from the single‐ and dual‐headed SPECT cameras were compared.Results: Reviewers localized areas of hyperperfusion with SISCOM images more often than with side‐by‐side SPECT evaluation (71.0 vs. 47.4%; p = 0.01). When we compared results of SPECT evaluation with traditional techniques, SISCOM showed greater concordance than side‐by‐side SPECT evaluation (60.53 vs. 36.84%; p = 0.006). There were no differences in localization between images derived from single‐ and dual‐headed cameras. Concordance of seizure localization, compared with traditional techniques, also was not different between these groups [κ = 0.38, 95% confidence interval (CI), 0.18–0.58] vs. κ = 0.63, 95% CI (0.45–0.81)].Conclusions: SISCOM is a worthwhile technique for preoperative evaluation in partial epilepsy patients and improves the sensitivity and specificity of seizure localization of SPECT images derived from both single‐ and dual‐headed SPECT cameras.
Early‐onset Cobalamin C/D Deficiency: Epilepsy and Electroencephalographic Features
Authors: Biancheri Roberta , Cerone Roberto , Rossi Andrea , Schiaffino Maria Cristina , Caruso Ubaldo , Minniti Giuseppe , Perrone Maria Viviana , Tortori‐Donati Paolo , Veneselli Edvige 
Published: March 2003

Summary:  Purpose: To describe epilepsy and EEG findings in the early‐onset cobalamin (Cbl) C/D deficiency, an inborn error of intracellular Cbl metabolism characterized by high plasma levels of methylmalonic acid, homocystine, and homocysteine.Methods: Type and frequency of seizures were studied in 10 patients (six boys and four girls) who underwent waking and sleep EEG.Results: Half of patients had seizures in the first year of life (either concurrent with the other symptoms of disease or some months after the onset of disease); seizures occurred after 2 years in the other half of patients. Convulsive status epilepticus was the initial manifestation in three patients. During the follow‐up, nine patients had seizures (mainly partial) despite specific treatment for Cbl C/D deficiency and antiepileptic drugs. Focal or multifocal epileptiform abnormalities during waking EEG that increased during sleep EEG were recorded in the majority of patients. Plasma levels of homocystine and homocysteine were constantly higher than normal, despite therapy institution.Conclusions: Epilepsy and EEG abnormalities are prominent features in the early‐onset type of combined methylmalonic aciduria and homocystinuria due to Cbl C/D deficiency, possibly related to the pathologically and persistently high levels of homocysteine, experimentally proven to induce seizures. Plasma amino acids evaluation and urinary acid organic analysis should be performed in any infant showing seizures associated with feeding difficulties and failure to thrive, at onset during the first year of life, as well as in any child with convulsive status epilepticus and a history of psychomotor developmental delay of unknown origin.
Topiramate and Phenytoin Pharmacokinetics During Repetitive Monotherapy and Combination Therapy to Epileptic Patients
Authors: Sachdeo R. C. , Sachdeo S. K. , Levy R. H. , Streeter A. J. , Bishop F. E. , Kunze K. L. , Mather G. G. , Roskos L. K. , Shen D. D. , Thummel K. E. , Trager W. F. , Curtin C. R. , Doose Dennis R. , Gisclon L. G. , Bialer Meir 
Published: March 2003

Summary:  Purpose: To evaluate the potential pharmacokinetic interactions between topiramate (TPM) and phenytoin (PHT) in patients with epilepsy by studying their pharmacokinetics (PK) after monotherapy and concomitant TPM/PHT treatment.Methods: Twelve patients with epilepsy stabilized on PHT monotherapy were enrolled in this study, with 10 and seven patients completing the phases with 400 and 800 mg TPM daily doses, respectively. TPM was added at escalating doses, and after stabilization at the highest tolerated TPM dose, PHT doses were tapered. Serial blood and urine samples were collected for PK analysis during the monotherapy phase or the lowest PHT dose after taper and the concomitant TPM/PHT phase. Potential metabolic interaction between PHT and TPM also was studied in vitro in human liver microsomal preparations.Results: In nine of the 12 patients, PHT plasma concentrations remained stable, with a mean (±SD) area under the curve (AUC) ratio (combination therapy/monotherapy) of 1.13 ± 0.17 (range, 0.89–1.23). Three patients had AUC ratios of 1.25, 1.39, and 1.55, respectively, and with the addition of TPM (800, 400, and 400 mg daily, respectively), their peak PHT plasma concentrations increased from 15 to 21 mg/L, 28 to 36 mg/L, and 27 to 41 mg/L, respectively. Human liver microsomal studies with S‐mephenytoin showed that TPM partially inhibited CYP2C19 at very high concentrations of 300 μM (11% inhibition) and 900 μM (29% inhibition). Such high plasma concentrations would correspond to doses in humans that are 5 to 15 times higher than the recommended dose (200–400 mg). TPM clearance was approximately twofold higher during concomitant TPM/PHT therapyConclusions: This study provides evidence that the addition of TPM to PHT generally does not cause clinically significant PK interaction. PHT induces the metabolism of TPM, causing increased TPM clearance, which may require TPM dose adjustments when PHT therapy is added or is discontinued. TPM may affect PHT concentrations in a few patients because of inhibition by TPM of the CYP2C19‐mediated minor metabolic pathway of PHT.
Acetoacetate, Acetone, and Dibenzylamine (a Contaminant in l‐(+)‐β‐Hydroxybutyrate) Exhibit Direct Anticonvulsant Actions in Vivo
Authors: Rho Jong M. , Anderson Gail D. , Donevan Sean D. , White H. Steve 
Published: March 2003

Summary:  Purpose: To investigate whether ketone bodies are directly anticonvulsant.Methods: We tested the effects of acetoacetate (ACA), acetone, and both stereoisomers, d‐(−)‐ and l‐(+), of β‐hydroxybutyrate (BHB) on sensory‐evoked seizures in Frings audiogenic seizure‐susceptible mice.Results: We found that these ketone bodies, with the exception of the d‐(−)‐isomer of BHB, were anticonvulsant in this model. Furthermore, with gas chromatography–mass spectrometry, we confirmed that the activity of l‐(+)‐BHB was due to dibenzylamine, a chemical contaminant.Conclusions: Our data indicate that the anticonvulsant efficacy of the ketogenic diet may be due in part to the direct actions of ACA and acetone.
Prediction of Seizure‐onset Laterality by Using Wada Memory Asymmetries in Pediatric Epilepsy Surgery Candidates
Authors: Lee Gregory P. , Park Yong D. , Hempel Ann , Westerveld Michael , Loring David W. 
Published: March 2003

Summary:  Purpose: Because the capacity of intracarotid amobarbital (Wada) memory assessment to predict seizure‐onset laterality in children has not been thoroughly investigated, three comprehensive epilepsy surgery centers pooled their data and examined Wada memory asymmetries to predict side of seizure onset in children being considered for epilepsy surgery.Methods: One hundred fifty‐two children with intractable epilepsy underwent Wada testing. Although the type and number of memory stimuli and methods varied at each institution, all children were presented with six to 10 items soon after amobarbital injection. After return to neurologic baseline, recognition memory for the stimuli was assessed. Seizure onset was determined by simultaneous video‐EEG recordings of multiple seizures.Results: In children with unilateral temporal lobe seizures (n = 87), Wada memory asymmetries accurately predicted seizure laterality to a statistically significant degree. Wada memory asymmetries also correctly predicted side of seizure onset in children with extra–temporal lobe seizures (n = 65). Although individual patient prediction accuracy was statistically significant in temporal lobe cases, onset laterality was incorrectly predicted in ≤52% of children with left temporal lobe seizure onset, depending on the methods and asymmetry criterion used. There also were significant differences between Wada prediction accuracy across the three epilepsy centers.Conclusions: Results suggest that Wada memory assessment is useful in predicting side of seizure onset in many children. However, Wada memory asymmetries should be interpreted more cautiously in children than in adults.
Hippocampal Programmed Cell Death after Status Epilepticus: Evidence for NMDA‐Receptor and Ceramide‐Mediated Mechanisms
Authors: Mikati Mohamad A. , Abi‐Habib Ralph J. , El Sabban Marwan E. , Dbaibo Ghassan S. , Kurdi Rana M. , Kobeissi Mohamad , Farhat Firas , Asaad Wissal 
Published: March 2003

Summary:  Purpose: Status epilepticus (SE) can result in acute neuronal injury with subsequent long‐term age‐dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE‐related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model.Methods: In adult rats, KA‐induced SE resulted in DNA fragmentation documented at 30 h after KA injection. Ceramide, a known mediator of PCD in multiple neural and nonneural tissues, increased at 2–3 h after KA intraperitoneal injection, and then decreased to control levels before increasing again from 12 to 30 h after injection. MK801 pretreatment prevented KA‐induced increases in ceramide levels and DNA fragmentation, whether there was reduction in seizure severity or not (achieved with 5 mg/kg and 1 mg/kg of MK801, respectively).Results: Both ceramide increases and DNA fragmentation were observed after KA‐induced SE in adult and in P35 rats. Ceramide did not increase after KA‐induced SE in P7 pups, which also did not manifest any DNA fragmentation. Intrahippocampal injection of the active ceramide analogue C2‐ceramide produced widespread DNA fragmentation, whereas the inactive ceramide analogue C2‐dihydroceramide did not.Conclusions: Our data support the hypotheses that (a) N‐methyl‐d‐aspartate–receptor activation results in ceramide increases and in DNA fragmentation; (b) ceramide is a mediator of PCD after SE; and (c) there are age‐related differences in PCD and in the ceramide response after SE. Differences in the ceramide response could, potentially, be responsible for observed age‐related differences in the response to SE.