bluuebunny/crossref_metadata_2025_split huggingface dataset:
The New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability
Authors: Marson A. G. , Kadir Z. A. , Hutton J. L. , Chadwick D. W. 
Published: August 2005

Summary: Purpose: Gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS) are all in use as “add‐on” treatment for patients with refractory epilepsy. There have been no comparative randomized controlled trials allowing an evidence‐based choice between these drugs. We report a series of meta‐analyses of randomized placebo‐controlled add‐on trials in which these drugs have been tested in patients with partial epilepsy. This work provides an estimate of each drug's efficacy and tolerability compared with placebo. These estimates are compared across drugs to give broad estimates of comparative efficacy and tolerability. Methods: Trial reports were found by searching Medline, by searching through journals by hand, and by contacting the pharmaceutical industry. The outcomes chosen were the proportion of patients who (a) have a 350% reduction in seizure frequency (50% responders); (b) withdrew from the study (any reason); or (c) reported the following side effects: ataxia, dizziness, fatigue, nausea, or somnolence. Overall odds ratio (OR) with 95% confidence intervals (CIS; 50% responders) or 99% CIS; side effects) were calculated. Results: Twenty‐nine trials were included, representing 4,091 randomized patients. The ORs for 50% response (95% CI) were GBP, 2.29 (1.53–3.43); LTG, 2.32 (1.47–3.68); TGB, 3.03 (2.01–4.58); TPM, 4.07 (2.87–5.78); VGB, 3.67 (2.44–5.51); and ZNS, 2.7 (1.36–4.47). ORs for discontinuation were GBP, 1.36 (0.75–2.49); LTG, 1.19 (0.79–1.79); TGB, 1.81 (1.21–2.70); TPM, 2.56 (1.64–4.00); VGB, 2.58 (126–5.27); and ZNS, 4.23 (1.71–10.49). Conclusions: We have clear evidence that each of these drugs is better than placebo at preventing seizures. When results are compared across drugs, the confidence intervals overlap, and we have no conclusive evidence of differences in efficacy or tolerability. Despite this, the agent that appears most effective may be twice as effective as the agent that appears least effective, and the agent that appears most likely to cause discontinuation may be 4 times more likely to do so than the treatment that appears least likely to do so. Comparative randomized studies are needed further to evaluate these drugs.
Tolerability and Pharmacokinetics of Monotherapy Felbamate Doses of 1,200–6,000 mg/day in Subjects with Epilepsy
Authors: Sachdeo Rajesh , Narang‐Sachdeo Satinder K. , Shumaker R. C. , Perhach J. L. , Lyness W. H. , Rosenberg A. 
Published: August 2005

Summary: Purpose: Felbamate (FBM) pharmacokinetic parameters, safety and tolerability in the dose range of 1,200–6,000 mg/day were assessed in two open‐label studies with similar designs. Methods: In study A, newly diagnosed subjects with epilepsy receiving FBM monotherapy at a starting dose of 1,200 mg/day (400 mg/three times daily, t.i.d.) and increased 1,200 mg/day, if tolerated, at 14‐day intervals to 3,600 mg/day were investigated. In study B, epilepsy subjects with prior FBM monotherapy exposure received ascending FBM doses in five consecutive 14‐day periods with a starting dose of 3,600 mg/day (1,200 mg t.i.d.) FBM. In each successive period, if FBM was well tolerated, the dose was increased by 600 mg/day to a maximum of 6,000 mg/day (2,000 mg t.i.d.). Results: The pharmacokinetic parameter estimates maximum observed concentration (Cmax), area under the concentration–time curve (AUCτ) Ctrough, and Cav showed a linear dependence to dose above the 1,200–6,000 mg/day FBM dose range (F‐tests; p <0.0001) with apparent clearance (Cl/kg) and Tmax (time to Cmax) independent of dose. When AUCτ, Cmaxand Ctroughwere adjusted for dose, there were no significant differences between the dosing periods. Conclusions: The data establish that plasma concentrations of FBM are linear with respect to dose to 6,000 mg/day. In addition, FBM was safely administered at these doses for periods as long as 14 days to epileptic subjects with prior exposure to FBM. FBM‐naive subjects appeared to report more adverse experiences (generally of mild to moderate severity) than did subjects with prior FBM exposure.
In Whom Does Status Epilepticus Occur: Age‐Related Differences in Children
Authors: Shinnar Shlomo , Pellock John M. , Moshé Solomon L. , Maytal Joseph , O'Dell Christine , Driscoll Susan M. , Alemany Marta , Newstein David , DeLorenzo Robert J. 
Published: August 2005

Summary: Purpose: Status epilepticus (SE) is an uncommon but potentially life‐threatening seizure. It is most common in children. Little is known about the differences within the pediatric age group in terms of the type of patient seen with SE. Methods: We analyzed the records of 394 children aged 1 month to 16 years who were part of two large studies of pediatric SE conducted in Bronx, New York, and Richmond, Virginia. The 394 children had a mean age of 4.4 years and included 349 (89%) with an initial episode of SE. Results: Status epilepticus was most common in younger children with > 40% of cases occurring in those younger than 2 years. The distribution of causes was highly age dependent. More than 80% of children younger than 2 years had SE of febrile or acute symptomatic origin, whereas cryptogenic and remote symptomatic causes were most common in older children (p <0.001). One hundred fifty‐eight (40%) of the cases were known to be previously neurologically abnormal, including 35 (21%) of 169 younger than age 2 years and 123 (55%) of 225 older than 2 years (p <0.001). One hundred seventy‐seven (45%) children had a history of seizures including 142 (41%) of the 349 children with a first episode of SE. A history of seizures was present in 34 (20%) of those younger than 2 years and 143 (64%) of those older than 2 years (p < 0.001). The effect of age remained significant even when the analysis was limited to those with SE of cryptogenic or remote symptomatic origin. Conclusions: There is a strong effect of age on the frequency and etiology of SE, as well as on the type of child who has SE. In young children, SE occurs primarily in children who are neurologically normal and with no history of unprovoked seizures. In older children, SE occurs primarily in those who are known to have prior unprovoked seizures and who are often also neurologically abnormal.
De Novo Aphasic Status Epilepticus
Authors: Grimes David Andrew , Guberman Alan 
Published: August 2005

Summary: The literature contains only a handful of reports of patients with aphasia as the principal or only obvious manifestation of partial status epilepticus. Even fewer patients of this type have been well documented both clinically and by ictal EEG monitoring. We studied an otherwise healthy woman with abrupt onset of aphasia initially thought to be the result of an infarct of the left temporoparietal area. We were able to document partial status epilepticus involving the left temporoparieta1 area with EEG/video monitoring and showed rapid reversal of the aphasic disorder with antiepileptic drug (AED) treatment. The case is presented with a review of previous reports to underscore the importance of considering this diagnosis in patients with abrupt onset of aphasia.
Locus Coeruleus Lesions Suppress the Seizure‐Attenuating Effects of Vagus Nerve Stimulation
Authors: Krahl Scott E. , Clark Kevin B. , Smith Douglas C. , Browning Ronald A. 
Published: August 2005

Summary: Purpose: Although vagus nerve stimulation (VNS) is now marketed throughout most of the world as a treatment for drug‐resistant epilepsy, the therapeutic mechanism of action of VNS‐induced seizure suppression has not yet been established. Elucidation of this mechanism is an important first step in the development of strategies to improve VNS efficacy. Because the locus coeruleus (LC) has been implicated in the antinociceptive effects of VNS, we chemically lesioned the LC in the present study to determine if it is a critical structure involved in the anticonvulsant mechanisms of VNS. Methods: Rats were chronically depleted of norepinephrine (NE) by a bilateral infusion of 6‐hydroxydopamine (6‐OHDA) into the LC. Two weeks later, they were tested with maximal electroshock (MES) to assess VNS‐induced seizure suppression. In another experiment, the LC was acutely inactivated with lidocaine, and seizure suppression was tested in a similar fashion. Results: VNS significantly reduced seizure severities of control rats. However, in animals with chronic or acute LC lesions, VNS‐induced seizure suppression was attenuated. Conclusions: Our data indicate that the LC is involved in the circuitry necessary for the anticonvulsant effects of VNS. Seizure suppression by VNS may therefore depend on the release of NE, a neuromodulator that has anticonvulsant effects. These data suggest that noradrenergic agonists might enhance VNS‐induced seizure suppression.
Incidence of Psychogenic Seizures in Adults: A Population‐Based Study in Iceland
Authors: Sigurdardottir Katrin Ruth , Olafsson Elias 
Published: August 2005

Summary: Purpose: We wished to determine the incidence of psychogenic nonepileptic (NES) seizures in a population‐based study. Methods: Cases were identified through review of the results of all long‐term video‐EEG studies made in Iceland during the study period. Results: The incidence of NES was 1.4 in 100,000 person‐years of observation. Age‐specific incidence was highest in the youngest age group (age 15–24 years) and decreased thereafter. A strong female preponderance was observed. Conclusions: The incidence of NES is equal to almost 4% of that reported for epilepsy from Iceland for persons aged ≥15 years. For people aged 15–24 years, the incidence of NES is equal to −5% of the incidence of epilepsy. Half the patients also had epilepsy.
Clinical Value of “Ictal” FDG‐Positron Emission Tomography and the Routine Use of Simultaneous Scalp EEG Studies in Patients with Intractable Partial Epilepsies
Authors: Barrington Sally F. , Koutroumanidis Michael , Agathonikou Alexander , Marsden Paul K. , Binnie Colin D. , Polkey Charles E. , Maisey Michael N. , Panayiotopoulos Chrysostomos P. 
Published: August 2005

Summary: Purpose: EEG is widely used during positron emission tomography (PET) to confirm the interictal state of the patient and assist in scan interpretation when a seizure occurs. Ictal scans usually reflect mixed interictal‐ictal‐postictal metabolic activity as seizures are brief in comparison to the 30‐min uptake period of the tracer. We wished to determine whether routine EEG is justified and if seizures commonly affect the diagnostic information of the PET scan. Methods: We examined the PET scans of 6 of 236 outpatients with intractable epilepsy with clinical and electrical evidence of a seizure during tracer uptake. We performed semi‐quantitative analysis in 2 patients who had “ictal” and control interictal scans. Results: Patients with single seizures lasting 23 s to 4 min [four complex partial seizures (CPS) and one absence seizure (AS)] had focal hypometabolism concordant with results of other investigations. One patient with complex partial status had irregular cortical uptake and focal hypometabolism, but the site of the ictal focus could not be confirmed. Conclusions: In this group of patients, seizures occurred infrequently during tracer uptake. The interpretation of the PET scan when single seizures occurred did not appear to be influenced by the continuous scalp EEG (CSEEG) recordings. The value of routine CSEEG in outpatients treated with medication should be reappraised, with potential cost savings. In rare circumstances in which a true ictal study occurs (complex partial status, epilepsia partialis continua, and repetitive CPS), PET scanning may be inconclusive and repeat interictal scanning should be pursued.
Prediction of Verbal Memory Loss in Individuals After Anterior Temporal Lobectomy
Authors: Davies Keith G. , Bell Brian D. , Bush Andrew J. , Wyler Allen R. 
Published: August 2005

Summary: Purpose: Decreased memory function represents the area of greatest neuropsychological morbidity after anterior temporal lobectomy (ATL), particularly for left ATL candidates. We wished to identify easily derived demographic and neuropsychological predictors of risk of pre‐to postoperative memory decline using only information available preoperatively. Methods: We assessed decline in memory as measured by the California Verbal Learning Test (CVLT) by deriving multiple regression equations using the following measures as independent variables: age at onset, chronological age at time of surgery, sex, Full Scale IQ (FSIQ), level of education, and preoperative memory scores. In all, 203 patients (93 males, 110 females), undergoing ATL (107 left, 96 right) with preoperative and 6‐month postoperative testing, were examined. Results: The combination of age, FSIQ, sex, side of surgery and preoperative score was highly predictive (p‐values <0.0001) of postoperative memory scores. Higher postoperative scores were associated with higher preoperative score, younger chronological age, higher FSIQ, female sex, and right side of resection. Reliable change index (RCI) values were used to estimate meaningful decline on the total score across five trials. Logistic regression analysis showed preoperative score and age to be predictors of RCI decline for left‐sided resections. Sensitivity of decline (≥90th centile RCI) prediction was 56%, and specificity was 95%. Validation in 30 patients from a separate population of patients undergoing left ATL produced similar figures. Conclusions: The derived regression equations can accurately predict verbal memory decline on a list‐learning task in‐50% of individual patients undergoing ATL, and false‐positive prediction errors are very rare.
Histopathological Correlates of Epileptogenicity as Expressed by Electrocorticographic Spiking and Seizure Frequency
Authors: Rosenow Felix , Lüders Hans O. , Dinner Dudley S. , Prayson Richard A. , Mascha Edward , Wolgamuth Barbara R. , Comair Youssef G. , Bennett Gregory 
Published: August 2005

Summary: Purpose: To study the correlation between histopathology and epileptogenicity, as measured by seizure frequency and electrocorticography (EcoG), in patients with cortical dysplasia (CD) as compared with control patients with gangliogliomas or gliomas. Methods: The influence of the histopathological classification and the presence of balloon cells in CD on the frequency and extension of five predefined patterns of ECoG spiking, seizure frequency, age of seizure onset and 6‐month postoperative outcome were analyzed in 32 patients with focal epilepsy undergoing presurgical evaluation with chronically implanted subdural electrodes. Results: Comparison of patients with CD, gangliogliomas, and gliomas showed that the seizure frequency was greatest in patients with CD and ECoG spiking and was most extensive in patients with gangliogliomas. The onset of epilepsy was earlier in patients with CD and with gangliogliomas. None of these differences was significant. However, in patients with CD, the presence of balloon cells was associated with significantly greater seizure frequency (p = 0.009), and a significantly greater number of electrodes recording continuous frequent spiking (p = 0.03). The presence of continuous very frequent spiking correlated with the duration of the epilepsy and the number of seizures recorded during monitoring. No significant correlation was detected between histopathology, seizure frequency, or ECoG activity and postoperative outcome, which was relatively favorable in patients with balloon cells. Conclusions: CD refers to a variety of histopathological patterns associated with different epileptogenicity. In CD, increased clinical and ECoG epileptogenicity correlates with the presence of balloon cells. This finding confirms that balloon cells should be considered in the histopathological classification of CD. The predefined ECoG were not specific for any of the histopathologies investigated.
Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine
Authors: III Allen Cato , Gustavson Linda E. , Qian Jiang , El‐Shourbagy Tawakol , Kelly Edward A. 
Published: August 2005

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB). Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one‐period (groups I‐IV) or a single dose, two‐period (group V) study (4‐mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I‐IV). TGB plasma concentrations and plasma protein binding were determined by high‐performance liquid chromatography (HPLC) and ultrafiltration, respectively. Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single‐dose mean values of the maximum plasma concentration, clearance, and half‐life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively. Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.
Long‐Term Follow‐Up of Childhood Epilepsy Associated with Tuberous Sclerosis
Authors: Ohtsuka Yoko , Ohmori Iori , Oka Eiji 
Published: August 2005

Summary: Purpose: To study the clinical and electroencephalographic (EEG) characteristics of patients whose epilepsy is associated with tuberous sclerosis, with special reference to their clinical course. Methods: We investigated the electroclinical and radiologic features of 38 patients with epilepsy associated with tuberous sclerosis. Results: Eleven patients showed only generalized epilepsy, and 10 showed only localization‐related epilepsy throughout their clinical course. Among the other 17 cases, the nature of the epilepsy changed between generalized and localization‐related epilepsies during the clinical course. A shift from generalized to localization‐related epilepsies was more common than the reverse. Seventeen had West syndrome (WS), three had Lennox‐Gastaut syndrome (LGS), and eight had epilepsies that evolved from WS to LGS. Tonic spasms, mostly in series, were seen in all 28 patients with generalized epilepsy. Eleven of the 28 patients had partial seizures and tonic spasms in the same period. Six of them showed “simultaneous seizures,” consisting of tonic spasms in series and a partial seizure. Partial seizures were the main seizure type in 27 patients with localization‐related epilepsy, but three of them also showed tonic spasms that included “simultaneous seizures.” Ictal EEGs revealed multiple active foci in the same period that could shift during the clinical course. Neither the location nor number of tubers was related to the clinical course. As for seizure outcome, 12 (32%) of 38 patients were free from seizures at follow‐up. Conclusions: In epilepsies associated with tuberous sclerosis, there may be an interrelation between generalized and localization‐related epilepsies, as well as one between generalized and partial seizures.
Medial Temporal Objective Lobe Epilepsy: Videotape Analysis of Clinical Seizure Characteristics
Authors: Williamson Peter D. , Thadani Vijay M. , French Jacqueline A. , Darcey Terrance M. , Mattson Richard H. , Spencer Susan S. , Spencer† Dennis D. 
Published: August 2005

Summary: Purpose: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. Methods: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. Results: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear Ictal speech and quick recovery were found when seizures originated in the non‐language‐dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language‐dominant hemisphere. Conclusions: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.
Patient Expectations of Temporal Lobe Surgery
Authors: Wilson Sarah J. , Saling Michael M. , Kincade Penny , Bladin Peter F. 
Published: August 2005

Summary: Purpose: The purpose of this study was to examine expectations of postoperative quality of life expressed by patients undergoing anterior temporal lobectomy (ATL) for the control of intractable seizures. An important component of this study was an exploration of the relationship between preoperative expectations and perceived success of the operation. Methods: Psychosocial functioning of 60 patients was assessed preand postoperatively, using a standardised, semistructured clinical interview. Preoperative assessment included a detailed examination of the patients' expectations of surgery, while postoperative assessment at 6 months examined the patients' perception of surgical success with respect to seizure outcome and postoperative psychosocial status. Results: A range of expectations were expressed about postoperative outcome. These were classified into 11 posthoc categories. Patients who perceived the operation as a success tended to endorse ‘practical’ expectations (i.e., driving, employment, activities) preoperatively, rather than expectations of a psychologic or social nature (i.e., self‐change, relationships). These patients experienced fewer postoperative seizures and psychosocial difficulties. In contrast, a perceived lack of success was associated with greater emphasis on psychosocial expectations preoperatively. These patients experienced a greater number of perceived postoperative psychosocial difficulties, and more postoperative seizures. Conclusions: Preoperative expectations of surgery formed an important baseline against which to assess postoperative outcome, and should constitute a routine part of assessment in studies of psychosocial outcome of ATL.
Aggressive Behaviour in Intellectually Challenged Patients with Epilepsy Treated with Lamotrigine
Authors: Beran Roy G. , Gibson Rebecca J. 
Published: August 2005

Summary: Purpose: Lamotrigine (LTG) is a valuable addition to the medical management of epilepsy with wide spectrum of efficacy and good outcomes for quality of life. We report the emergence of a syndrome of aggressive behavior provoked by LTG in patients with epilepsy and intellectual challenge. Methods: On recognition of a tendency to aggression in intellectually challenged patients whose epilepsy was treated with LTG, a survey was conducted of those from centers specializing in management of patients with intellectual disability who were treated with LTG. Responses to LTG were sought and patient's behavioral profiles were determined. Results: Nineteen patients were identified (16 men, 3 women, aged 17–54 years). Five patients discontinued LTG due to unprovoked aggressive behavior subsequent to its use; 2 had aggressive behavior sufficient to justify discontinuation of LTG but required reintroduction to control the epilepsy; 1 required reduction in LTG dosage; 1 had aggression that responded to psychiatric intervention; and I had aggression unrelated to LTG. Four patients had behavioral problems other than aggression, 4 had no change in behavior, and the behavior of 1 was improved by LTG treatment.