bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentrations and Effects of Oral Midazolam are Greatly Reduced in Patients Treated with Carbamazepine or Phenytoin
Authors: Backman Janne T. , Olkkola Klaus T. , Ojala Mikael , Laaksovirta Hannu , Neuvonen Pertti J. 
Published: August 2005

Summary:Midazolam is a short‐acting benzodiazepine which is used as an oral hypnotic agent in several countries. We studied the pharmacokinetic and pharmacody‐namic aspects of an oral 15–mg dose of midazolam in 6 patients with epilepsy who are also taking carbamazepine (CBZ) or phenytoin (PHT). We compared results with those obtained in 7 noninduced control subjects. Plasma concentrations and effects of midazolam were measured for 10 h. In patients with epilepsy, the area under the plasma concentration‐time curve (AUC) of midazolam (mean 2 SEM) was only 5.7% (0.60 ± 0.16 vs. 10.5 ± 0.6 μg ‐ min/ml), and the peak midazolam concentration was 7.4% (5.2 ± 1.2 vs. 70.4 ± 9.0 μg/ml) of its value in control subjects (p < 0.001). The elimination half‐life (t1/2) of midazolam was 1.3 ± 0.2 h in patients and 3.1 ± 0.1 h in controls (p < 0.001). The low plasma midazolam concentrations in the patient group were associated with reduced pharmacodynamic effects as compared with control subjects [e.g., the Critical Flicker Fusion Test (CFFT), p < 0.05]. Induction of CYP3A (cytochrome P‐450IIIA) enzymes by CBZ and PHT is the most likely explanation of the great difference in the pharmacokinetic and pharmacodynamic profiles of oral midazolam in the two groups.
Relapse and Survival After Barbiturate Anesthetic Treatment of Refractory Status Epilepticus
Authors: Krishnamurthy Kaarkuzhali B. , Drislane Frank W. 
Published: August 2005

Summary: Purpose: Pentobarbital is standard treatment for refractory status epilepticus (SE) and is almost uniformly effective, but the morbidity of treatment and the mortality of refractory SE are high. Recurrence of SE after pentobarbital discontinuation may predict a worsened outcome. We sought to determine the optimal use of barbiturate anesthetic treatment of refractory SE.Methods: We reviewed 44 episodes of barbiturate anesthetic treatment for refractory SE in 40 patients, seeking factors predicting freedom from relapse to clinical or electrographic SE after treatment and predicting survival.Results: Eight of 9 patients with relapse of seizures after barbiturate treatment died, whereas only 9 of 26 with persistently controlled seizures died (p < 0·005). Both likelihood of relapse and survival correlated strongly with etiology, with 19 of 20 patients with chronic epilepsy, infections, or focal lesions having good control as compared with 2 of 9 with multiple medical problems (p < 0·001). Treatment delay did not predict a worsened outcome. Hypotension caused dose reduction but never required treatment discontinuation. Patients with more prolonged treatment and those receiving phenobarbital (PB) at the time of pentobarbital taper were less likely to relapse.Conclusions: Relapse of SE after barbiturate anesthetic treatment is a poor prognostic sign and should be prevented, if possible. Etiology was the primary predictor of outcome, but more prolonged treatment and the use of PB during pentobarbital withdrawal appeared to provide protection against relapse.
On the Structure of Ictal Events in Vitro
Authors: Traub Roger D. , Borck Cornelius , Colling Simon B. , Jefferys John G. R. 
Published: August 2005

Summary: Purpose: To analyze the cellular and network mechanisms of sustained seizures, we reviewed the literature and present new data on in vitro epileptiform events. We considered single and recurring synchronized population bursts occurring on a time scale from tens of milliseconds to I min.Methods: We used intracellular and field potential recordings, together with computer network simulations, derived from three types of experimental epileptogenesis: γ‐aminobutyric‐acidA, (GABAA) blockade, low extracellular [Mg2+]0, and 4‐aminopyridine (4‐AP).Results: In all three models, sustained depolarizing synaptic currents developed, either through N‐methyl‐D‐aspartate (NMDA) receptors, depolarizing GABAA, receptors, or both. Ectopic action potentials (APs), probably originating in axonal structures, occurred in 4‐AP and (as shown by other researchers) after tetanic stimulation; ectopic APs, occurring at sufficient frequency. should also depolarize dendrites, by synaptic excitation, enough to trigger bursts.Conclusions: Ictal‐like events appear to arise from two basic mechanisms. The first mechanism consists of sustained dendritic depolarization driving a series of dendritic bursts. The second mechanism consists of an increase in axonal and presynaptic terminal excitability driving a series of bursts analogous to interictal spikes.
Sudden Unexplained Death Among Subjects with Refractory Epilepsy
Authors: Derby Laura E. , Tennis Patricia , Jick Hershel 
Published: August 2005

Summary: Purpose: To address concerns about possible increases in rates of sudden unexplained death (SUD) after use of new anticonvulsants, more information on the rate of SUD among subjects with refractory epilepsy is needed to provide a comparison. Methods: We conducted a study to estimate the incidence of SUD among subjects younger than 50 years with refractory epilepsy, by using information from the General Practice Research Database (GPRD) in the United Kingdom. For the purposes of this study, subjects receiving two or more anticonvulsant drugs concurrently were considered to have refractory epilepsy. Potential cases of SUD were identified from the computer records, and clinical records for these subjects were reviewed by two specialists in SUD in epilepsy. Results: Fifteen subjects (eight male, seven female) of the 4,150 subjects with refractory epilepsy were considered to have definite/probable or possible SUD. Conclusions: The overall incidence rate of SUD in the population was 2.2 per 1,000 person‐years (95% CI, 1.3–3.6). The rate for subjects with highly probable SUD was 1.5 per 1,000 person‐years (95% CI, 0.8–2.7).
Concurrent Illnesses in Adults with Childhood‐Onset Epilepsy: A Population‐Based 35‐Year Follow‐Up Study
Authors: Jalava Merja , Sillanpää Matti 
Published: August 2005

Summary: Purpose: To ascertain the occurrence of concurrent illnesses in adults with epilepsy since childhood. Method: After a mean follow‐up of 35 years of a prospective, population‐based long‐term followed patient cohort with epilepsy since childhood, comorbidity was examined in 176 surviving (100 of them with epilepsy only) and 44 dead patients and in random and employee controls. Results: Somatic comorbidity varied from 84 to 95% in patients and from 67 to 74% in controls. No significantly increased risk of somatic diseases could be shown. Psychosomatic disorders were associated in 46‐74% of patients and in 42‐75% of controls, and psychiatric disorders were associated in 11‐23% of patients and in 7% of controls. As compared with random controls, patients with epilepsy had only a 4.0‐ to 4.2‐fold risk of psychiatric disorders or of combinations of somatic, psychosomatic, and/or psychiatric disorders. Patients received psychotropic drugs 8.6 times more frequently than employee controls. The risk for psychiatric and psychsomatic disorders was higher than expected in patients with childhood‐onset epilepsy, regardless of whether or not they were still receiving antiepileptic drugs (AEDs). Conclusion: Epilepsy per se, but not AEDs, has an apparent association with the occurrence of psychiatric and psychosomatic disorders. Risk for somatic comorbidity is not increased.
The Functional Organization of the Interictal Spike Complex in Benign Rolandic Epilepsy
Authors: Baumgartner Christoph , Graf Martin , Doppelbauer Andreas , Serles Wolfgang , Lindinger Gerald , Olbrich Achim , Bacher Johanna , Pataraia Ekaterina , Almer Gabriele , Lischka Andreas 
Published: August 2005

Summary: Purpose: We studied the functional organization of the interictal epileptic spike complex in patients with benign rolandic epilepsy of childhood (BREC). Methods: We recorded interictal epileptiform spikes and somatosensory evoked potentials after median nerve stimulation, providing a biologic marker for the location of the central sulcus in 12 patients with BREC. We used multiple dipole modeling to assess the number, the three‐dimensional intracerebral location, and the time activity of the underlying neuronal sources. Results: Although the interictal spike complex could be modeled by a single tangential dipolar source in seven patients (group 1), in the remaining five patients, two sources—a radial and a tangential dipole—were necessary adequately to explain the interictal spikes (group 2). The tangential source was located deeper than the radial source and was characterized by a frontal positivity and a centroparietal negativity with a phase reversal across the central sulcus, suggesting that the interictal spikes originated in the anterior wall of the central sulcus. The radial source showed a single electronegativity over the ipsilateral central region, which would be compatible with involvement of the top of either the pre‐ or postcentral gyrus. Both sources showed biphasic time patterns with an average latency difference of 30 ms. Conclusions: Our results indicate that in some patients with typical BREC, the interictal epileptiform spike complex is generated by multiple, simultaneously active neuronal populations within the central region and that epileptiform activity is propagated between these two adjacent cortical areas.
Evaluation of Carbamazepine and Carbamazepine‐Epoxide Protein Binding in Patients Undergoing Epilepsy Surgery
Authors: Gidal Barry E. , Spencer Nancy W. , Maly Melissa M. , Pitterle Michael E. 
Published: August 2005

Summary:Carbamazepine (CBZ) serum concentrations increase after epilepsy surgery. A possible mechanism may be acute changes in protein binding, specifically those involving the acute phase reactant α1‐acid glycoprotein (AAG). We prospectively evaluated 16 adults (11 receiving CBZ) with epilepsy (mean age 30 ± 8.9 years, 8 women and 8 men) undergoing temporal lobe resections and characterized AAG, albumin, CBZ, and CBZ‐epoxide (CBZ‐E) free fractions over time. AAG, ALB, CBZ, and CBZ‐E free fractions were determined before surgery (baseline) and on postoperative days 1–5, 14, and 30. AAG was measured with a radial immunodiffusion assay method, CBZ and CBZ‐E serum concentrations were determined by high‐performance liquid chromatography (HPLC). Free fractions of CBZ and CBZ‐E were calculated as the ratio of unbound (determined after ultracentrifugation) to total serum drug concentrations. Statistical analysis included analysis of variance (ANOVA) and Student's t test for paired data when appropriate, with significance assigned at p < 0.05. All data are mean ± SD. AAG concentrations increased significantly from baseline (61.9 ± 21.3 mg/dl), peaking at postoperative day 3 (116.8 ± 20.6 mg/dl) and decreasing to baseline levels between days 14 and 30. CBZ serum concentrations were significantly increased in the immediate postoperative period (day 3), but albumin concentrations and CBZ and CBZ‐E free fractions did not differ significantly between baseline and the postoperative time points. Temporal lobe resection results in an acute phase reaction which is manifested in part by significant changes in AAG. Although CBZ and CBZ‐E total serum concentrations increased significantly in the immediate postoperative period, epilepsy surgery did not appear to result in significant overall changes in drug binding to plasma proteins.
Routine EEG and Temporal Lobe Epilepsy: Relation to Long‐Term EEG Monitoring, Quantitative MRI, and Operative Outcome
Authors: Cascino Gregory D. , Trenerry Max R. , So Elson L. , Sharbrough Frank W. , Shin Cheolsu , Lagerlund Terrence D. , Zupanc Mary L. , Jack Clifford R. 
Published: August 2005

Summary: Purpose: To investigate the relation among routine EEG, long‐term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE). Methods: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake‐sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator. Results: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p < 0.0001) and the results of MRI volumetric studies (p < 0.0001). Interictal epileptiform discharges were seen only during LTM in 24 patients. Routine EEG was disconcordant with interictal LTM in another 20 patients. MRI‐identifed unilateral medial temporal lobe atrophy was a strong predictor of operative success (p < 0.0001). There was no significant relation between the routine EEG findings and operative outcome (p > 0.20). Conclusions: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI‐identified unilateral medial temporal lobe atrophy.
Paroxysmal Staring and Masticatory Automatisms During Postural Hypotension in a Patient with Multiple System Atrophy
Authors: Iani Cesare , Attanasio Antonio , Manfredi Mario 
Published: August 2005

Summary: Purpose: We studied a 51‐year‐old man with multiple system atrophy and autonomic insufficiency. He had repeated episodes of loss of contact, staring, and masticatory automatisms. Methods: Blood pressure during these events documented a systolic pressure of 60 mm Hg. Cardiovascular reflex tests provided evidence of autonomic failure. Head computed tomography (CT) revealed moderate, diffuse cortical and cerebellar atrophy. Results: These events were strictly related to blood pressure decreases and could be reproduced consistently by having the patient sit up after a meal. Ictal polygraphic recordings showed EEG changes consistent with anoxia, preceded by sudden hypotension with fixed heart rate. Conclusions: Cerebral anoxia during a syncopal attack may therefore precipitate transient, sudden neurologic dysfunction that closely mimics complex partial seizures. Masticatory automatisms may represent a release phenomenon resulting from inactivation of neocortical structures by cerebral anoxia or reticular disconnection.
Partial Epileptic Seizures of Different Origin Variably Affect Cardiac Rhythm
Authors: Galimberti Carlo Andrea , Marchioni Enrico , Barzizza Franco , Manni Raffaele , Sartori Ivana , Tartara Amelia 
Published: August 2005

Summary: Purpose: The present study was aimed at evaluating electrocardiographic (ECG) changes associated with partial epileptic seizures without seizure activity secondarily generalized. Methods: We assessed heart rate (HR) changes occurring during 100 partial epileptic seizures, as recorded by ambulatory EEG‐ECG in 50 outpatients. Consecutive R‐R intervals were measured for the 30 s immediately preceding the onset and for the first 10‐s period of discharge. In addition, HR was sampled at 10‐s intervals during EEG paroxysmal discharge and for 1 min after the end of discharge. Results: The highest and lowest respective HR peaks achieved during these seizures were 186 and 44 beats/min. Analysis of the R‐R intervals during the first 10‐s period of EEG discharge showed a significant early HR increase in 49% of the seizures; the corresponding figure for an early HR reduction was 25.5%. Eighty percent of the seizures showing an early HR decrease were of temporal lobe origin. No severe cardiac arrhythmias were noted during the seizures. Conclusions: Our data suggest that an early HR decrease is more probable in temporal lobe seizures than in seizures of other origin. An accurate HR measurement, focused on discharge onset, may provide both a reliable way of evaluating the possible effect of partial seizures on HR and valuable information about the cerebral sites involved in the control of cardiac rhythm.
Double‐Blind, Placebo‐Controlled Trial of Topiramate (600 mg Daily) for the Treatment of Refractory Partial Epilepsy
Authors: Tassinari C. A. , Michelucci R. , Chauvel P. , Chodkiewicz J. , Shorvon S. , Henriksen O. , Dam M. , Reife R. , Pledger G. , Karim R. 
Published: August 2005

Summary: Purpose: We wished to evaluate adjunctive therapy for partial‐onset seizures with topiramate (TPM) for efficacy and safety in a double‐blind, placebo‐controlled, randomized, parallel‐group study. Methods: Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial‐onset seizures with or without secondarily generalized seizures. After an 8‐week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks. Results: TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. ‐12%, p = 0.004); greater number of treatment responders (patients with 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM‐treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity. Conclusions: The results of the present trial indicate that TPM 600 mgiday is effective in the treatment of refractory partial‐onset seizures with or without secondarily generalized seizures.
Steady‐State Pharmacokinetics of Topiramate and Carbamazepine in Patients with Epilepsy During Monotherapy and Concomitant Therapy
Authors: Sachdeo Rajesh C. , Sachdeo S. K. , Walker S. A. , Kramer L. D. , Nayak R. K. , Doose D. R. 
Published: August 2005

Summary: Purpose: We studied the steady‐state pharmacokinetic profile of topiramate (TPM) as a function of dose and the effects of comedication with carbamazepine (CBZ). Methods: We enrolled 12 patients with partial epilepsy receiving chronic stable doses of CBZ 300–800 mg every 8 h. In a 6‐week period, TPM was added and doses were increased at ‐2‐week intervals from 100 to 200 to 400 mg every 12 h and stabilized at the highest tolerated dose to as high as 400 mg every 12 h. CBZ was tapered in the next 4 weeks when possible, and TPM was maintained as monotherapy at the highest stabilized dose for 2 more weeks. Plasma and urine samples were collected before TPM dosing, after each TPM dose increase, and during TPM monotherapy. Results: Dose‐normalized results (n = 10) for TPM area under the curve from 0 to 12 h (AUC(0–12)), Cmin(0), and Cavg indicated that TPM exhibits linear plasma pharmacokinetics over the dose range of 100‐ to 400‐mg every 12 h when administered with CBZ. Mean TPM AUC(0–12)) Cmax, Cmin(0), and Cavg values were ‐40% lower during CBZ treatment as compared with those during TPM monotherapy (n = 3). TPM oral and nonrenal clearance rates were approximately two‐ to threefold higher, whereas TPM renal clearance was unchanged during concomitant CBZ treatment (n = 3). There were no significant changes in total and unbound CBZ and CBZ‐epoxide (CBZ‐E) pharmacokinetics during TPM administration (n = 10). TPM pharmacokinetics during concomitant CBZ treatment were significantly different from those during TPM monotherapy, suggesting that metabolic clearance of TPM increases when CBZ is coadministered. Conclusions: When CBZ is reduced or discontinued, TPM doses may need to be lowered to maintain equivalent plasma concentrations. Adjusting the CBZ dose for pharmacokinetic reasons when TPM is administered as adjunctive treatment does not appear to be necessary.
Prevalence, Classification, and Severity of Epilepsy and Epileptic Syndromes in Children
Authors: Eriksson K. J. , Koivikko M. J. 
Published: August 2005

Summary:Purpose:To determine the point prevalence of active childhood epilepsy in a defined area and evaluate the usefulness of ILAE classification of seizures, and epilepsies/syndromes with special interest in severe epilepsies.Methods:By using the latest ILAE International Classification of Epileptic Seizures (ICES, 1981) and Epilepsies and Epileptic Syndromes (ICE, 1989), we determined the age‐ and sex‐specific prevalence rates of epilepsy, type of seizures, epilepsies, and recognizable epileptic syndromes, as well as the proportion of severe cases in each seizure/epilepsy/syndrome category in all children 0–15 years of age from a geographically defined area in Finland. All medical records, neurophysiological recordings and available clinical data were reviewed retrospectively.Results:Point prevalence of active epilepsy on December 12, 1992 was 3.94 per 1,000. According to ICESDCE, we were able to classify 96% of seizures and 90% of epilepsies and syndromes. Generalized seizure and epilepsy/syndrome types were more prevalent in children 0–6 years of age and partial/ localization‐related in children 6–15 years of age. Epilepsy was intractable in 17% of all cases and correlated significantly with symptomatic etiology and early onset of epilepsy, as well as with additional neuroimpairments.Conclusions:A considerable number of cases fell into the nonspecific categories of ICE, which limits the value of present epilepsy/syndrome classification in terms of prognosis, prediction, and indication for special investigations in individual cases. A number of intractable cases was relatively low, indicating good prognosis in many childhood epilepsies, especially when additional neuroimpairments are absent.
Prevalence and Descriptive Epidemiology of Lennox‐Gastaut Syndrome Among Atlanta Children
Authors: Trevathan Edwin , Murphy Catherine C. , Yeargin‐Allsopp Marshalyn 
Published: August 2005

Summary: Purpose: To determine the prevalence and descriptive epidemiology of Lennox‐Gastaut Syndrome (LGS) among metropolitan Atlanta children.Methods: We conducted a population‐based study of LGS as part of the Metropolitan Atlanta Developmental Disabilities Study (MADDS) using a multiple‐source surveillance system for epilepsy and developmental disabilities. Children were defined as having LGS if they had onset of multiple seizure types before age 11 years, with at least one seizure type resulting in falls, and an EEG demonstrating slow spike‐wave complexes (<2.5 Hz). Mental retardation (MR) was not used as a diagnostic criterion.Results: The lifetime prevalence of LGS at age 10 years was 26/1,000. Ninety‐one percent of those with LGS had MR (IQ <= 70), and 39% had a history of infantile spasms (IS). A comparison of children with LGS and those with multiple seizure types without slow spike‐wave complexes demonstrated that those with LGS were more likely to have MR, history of IS, and multiple disabilities (MR, cerebral palsy, blindness, hearing impairment). Seventeen percent of all children in Atlanta with profound MR (IQ < 20) had LGS.Conclusions: LGS accounts for only 4% of all childhood epilepsy, yet is a significant contributor to childhood morbidity.