bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Family with Hereditary Spastic Paraparesis and Epilepsy
Authors: Webb Stewart , Flanagan Niamh , Callaghan Noel , Hutchinson Michael 
Published: August 2005

Summary: Purpose: We describe a family with hereditary spastic paraparesis (HSP) in which 4 of 6 affected members also have epilepsy.Methods: All family members were examined by 2 neurologists. Four affected and 3 unaffected family members had EEG recordings. Four affected members were investigated for other causes of spastic paraparesis and epilepsy.Results: Epileptic symptoms varied among family members: 1 had complex partial seizures, another had focal myoclonic epilepsy, and 2 had simple partial seizures secondarily generalized. All 4 had clinical or EEG evidence to support a focal origin for the epilepsy, and 2 had photoparoxysal responses on EEG. Symptoms were more severe and occurred earlier in the younger generation, suggesting genetic anticipation in this family. The onset of epilepsy developed simultaneously with, or ≤18 years before, onset of gait disturbance. Three unaffected family members had normal EEGs.Conclusions: The association of HSP and epilepsy should no longer be assumed to be fortuitous.
Population Analysis of the Pharmacokinetics of Tiagabine in Patients with Epilepsy
Authors: Samara E. E. , Gustavson L. E. , El‐Shourbagy T. , Locke C. , Granneman G. R. , Sommerville K. W. 
Published: August 2005

Summary: Purpose: In two open‐label long‐term safety studies, we determined tiagabine (TGB) pharmacokinetics in patients with epilepsy. Methods: In all, 2,147 plasma samples from 511 patients who participated in the studies were available. The total daily dose ranged from 2 mg administered once daily to 80 mg administered in four doses. A one‐compartment model with first‐order absorption and elimination was used to fit the TGB plasma concentration‐time data, with a population pharmacokinetic approach. Results: The patients’average (±SD) weight and age were 73.8 ± 20.7 kg and 32.1 ± 12.3 years. The most significantly factor affecting TGB pharmacokinetics was concomitant administration of other antiepileptic drugs (AEDs). The central clearance value in patients receiving AEDs known to induce hepatic drug metabolism was 21.4 L/h, a value 67% higher than the central clearance estimate obtained for the patients receiving AEDs not known to affect hepatic drug metabolism (12.8 L/h). There was no evidence of any dose or time effect, indicating that TGB pharmacokinetics are linear. TGB pharmacokinetics were not different in white, black, or Hispanic patients, although our ability to explore racial effects was limited since 90% of the patients were white. No other demographic variables (including age and smoking) or any clinical chemistry measurements (including bilirubin, SGOT, and SGPT) were important in explaining the variability in the clearance estimates. Conclusions: TGB pharmacokinetics are linear, influenced by enzyme‐inducing AEDs, and largely unaffected by other demographic variables.
Role of Vigabatrin and Lamotrigine in Treatment of Childhood Epileptic Syndromes
Authors: Béanger Stacey , Coulombe Geneviève , Carmant Lionel 
Published: August 2005

Summary: Purpose: Vigabatrin (VGB) and lamotrigine (LTG) are two new antiepileptic drugs (AEDs) with different mechanisms of action for treatment of refractory epilepsies. Previous reports have indicated efficacy of both drugs in a number of epileptic syndromes. Methods: We compared these new AEDs drugs to determine their respective efficacy against different types of epileptic syndrome and to develop a rational approach to their use. We reviewed the charts of 105 children, with partial and generalized epilepsies. Results: VGB was to be significantly more effective in children with partial epilepsies, and LTG was more effective in those with generalized epilepsies. Conclusions: VGB and LTG have different therapeutic profiles. Combination treatment with the two drugs may represent rational polytherapy for patients with epilepsy resistant to treatment with either drug alone or as add‐on to other AED treatment.
Proton Magnetic Resonance Spectroscopic Imaging in Patients with Extratemporal Epilepsy
Authors: Stanley Jeff A. , Cendes Fernando , Dubeau François , Andermann Frederick , Arnold Douglas L. 
Published: August 2005

Summary: Purpose: Reduced levels of N‐acetylaspartate (NAA) in temporal lobes responsible for temporal lobe epilepsy have been observed consistently in proton magnetic resonance spectroscopy (MRS) studies. Methods: We investigated the potential of proton MRS to detect low NAA outside of the temporal lobes in patients with non‐lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI) data of both frontal lobes and central/postcentral regions were obtained in 20 such patients and 16 normal control subjects. The epileptogenic region was determined by an extensive clinical‐EEG investigation, including the recording of habitual seizures in each patient, and intracranial EEG recordings in 10 patients. Results: The relative NAA resonance intensities (i.e., NAN/phosphocreatine plus creatine (CRt), NAN/choline‐containing metabolites (Chot) and NAA/Crt+ Chot), were all significantly reduced throughout the spectroscopic image as compared with that of the controls. Furthermore, reduction of the NAA ratios was greater in the epileptogenic region as compared with the nonepileptogenic regions, on EEG investigation. Conclusions: In vivo proton MRSI of patients with nonlesional partial extratemporal epilepsy detected evidence of widespread neuronal damage or dysfunction that was greatest in the region of seizure focus.
Pharmacokinetic Evaluation of Twice‐Daily Extended‐Release Carbamazepine (CBZ) and Four‐Times‐Daily Immediate‐Release CBZ in Patients with Epilepsy
Authors: Garnett William R. , Levy Benjamin , McLean Angus M. , Zhang Yuxin , Couch Richard A. , Rudnic Edward M. , Pellock John M. , Belendiuk George W. 
Published: August 2005

Summary: Purpose: A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate‐release, extended‐release, and enteric‐release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended‐release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate‐release formulation of CBZ four times daily. Methods: The randomized, double‐blind, two‐way, cross‐over study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2‐week period, blood samples were obtained hourly for a 24‐h period. Results: The 90% confidence intervals (CI) of the ratio of the means of the extended‐release formulation twice daily to the immediate‐release formulation four times daily were within the range of 0.80–1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ‐epoxide (CBZ‐E). There was no difference in the frequency of seizures between treatment (p = 0.103). Conclusions: Our results demonstrate that extended‐release CBZ twice daily was bioequivalent to immediate‐release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ‐E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency.
Comparison of Single‐ and Repeated‐Dose Pharmacokinetics of Diazepam
Authors: Walker M. C. , Tong X. , Brown S. , Shorvon S. D. , Patsalos P. N. 
Published: August 2005

Summary: Purpose: To determine whether repeat boluses of diazepam (DZP) lead to significant accumulation in the central nervous system and/or peripheral compartments, as repeat intravenous boluses of diazepam are commonly used in the treatment of status epilepticus (SE). Methods: In a rat model that permits simultaneous serum and cerebrospinal fluid (CSF) sampling, we characterized the pharmacokinetics of DZP and its metabolite, desmethyldiazepam, in CSF and blood using HPLC. DZP was administered by intraperitoneal injection as either a single dose (20 or 30 mg/kg) or repeat doses (10 or 20 mg/kg × 3, 1 h apart). Results: After a single intraperitoneal dose, DZP was rapidly absorbed with a time to maximum concentration of 10 min. The serum concentrations then declined biexponentially. DZP rapidly entered the CSF; the CSF to serum ratio reached equilibrium within 10 min, and was equivalent to the ratio of free to total serum concentration. Repeated DZP dosing resulted in a threefold decrease in volume of distribution and clearance (p < 0.001). This was reflected in the CSF concentration data; how‐ever, after the third dose, the ratio of CSF to serum concentration, also increased greatly, representing further persistence of DZP in the CSF compartment. Conclusions: Repeat dosing of DZP leads to substantial accumulation, and high, persistent serum and CSF concentrations, which may explain the toxic effects of repeat DZP dosing. Repeat dosing of DZP using a tapering protocol, however, may increase the effectiveness of DZP in treating SE by preventing relapses without substantially increasing toxicity.
Astrocytes from Human Hippocampal Epileptogenic Foci Exhibit Action Potential–Like Responses
Authors: O'Connor Edward R. , Sontheimer Harald , Spencer Dennis D. , de Lanerolle Nihal C. 
Published: August 2005

Summary: Purpose: We studied Na+ channel expression and the ability to generate action potential (AP)‐like responses in primary cultures of human astrocytes by whole cell patchclamp recording techniques. Methods: Tissue samples from 22 patients with various classifications of temporal lobe epilepsy (TLE) were plated to form separate astrocyte cultures from three regions; the hippocampus, parahippocampus, and anterolateral temporal neocortex. Results: The resting membrane potential of seizure focus astiocytes (MTLE, mesial TLE) was significantly depolarized (approximately ‐55 mV) as compared with cortical astrocytes (‐80 mV). Hippocampal astrocytes from other substrates for TLE (MaTLE, mass‐associated TLE; PTLE, paradoxical TLE) in which the hippocampus is not the seizure focus displayed resting membrane potentials similar to those of neocortical astrocytes (approximately ‐75 mV). Astrocytes from the seizure focus (MTLE) displayed much larger tetrodotoxin (TTX)‐ sensitive Na+ currents with ‐66‐fold higher Na+ channel density (113.5 ± 17.41 pA/pf) than that of comparison neocortical astrocytes (1.7 ± 3.7 pA/pf) or than that of the hippocampal and parahippocampal astrocytes of the MaTLE and PTLE groups. As a consequence of this higher channel density, seizure focus astrocytes were capable of generating AP‐like responses. However, at the resting potential, most Na+ channels are inactive and no spontaneous firing was observed. In contrast, astrocytes in the comparison neocortex from all groups and the hippocampus and parahippocampus from the MaTLE and PTLE groups could not fire AP‐like responses even after large current injections. Conclusions: The function of Na+ channels in these astrocytes is unclear. However, the marked differences in seizure focus astrocytes as compared with cortical and nonseizure focus hippocampal astrocytes suggest a more active role for astrocytes associated with hyperexcitable neurons at a seizures focus.
Functional Plasticity After Left Anterior Temporal Lobectomy: Reconstitution and Compensation of Verbal Memory Functions
Authors: Helmstaedter C. , Elger C. E. 
Published: August 2005

Summary:Purpose:This study investigated the functional plasticity of the brain to reconstitute and compensate for verbal memory functions after epilepsy surgery of left temporocortical and temporomesial structures. We hypothesized that memory outcome would be best when surgery is performed within the period of cerebral plasticity, and that the outcome should be worst when fluid intelligence starts to decrease with physiologic aging. We also raised the question of different plasticity and compensation mechanisms for temporomesial and temporocortical memory functions.Methods: We evaluated preoperative and l‐year‐post‐ operative memory data and other verbal functions in 104 patients with epilepsy, who underwent a standard left anterior temporal lobe. resection. We used memory measures that had been previously shown to be most selective for mesial and lateral functions, respectively. Determinants of postoperative memory outcome were evaluated by multiple regression analysis. Group statistics were calculated on the basis of the periods that are usually assumed to be significant for plasticity and behavioral compensation. Individual postoperative changes in memory functions were evaluated on the basis of test‐retest data obtained in a group of 100 non‐surgical patients with localization‐related epilepsies (mean retest interval >12 months).Results:Only changes in cortically represented learning and data acquisition were related to age, plasticity, and capacities for behavioral compensation. No patient in the youngest group (younger than 15 years), 33% of patients who had surgery between the ages of 15 and 30 years, and 61% of the patients undergoing surgery older than age 30 years had significant deterioration in verbal learning. In contrast, postoperative changes in temporomesial consolidation/retrieval processes were independent of age at the time of surgery, plasticity, and capacities for behavioral compensation.Conclusions:Our data indicate different time windows for the reconstitution and compensation of mesial and cortical as‐ pects of memory. Whereas the reconstitution of and compensation for cortical functions appear restricted by decreasing plasticity and physiological aging, mesial functions seem to be reconstituted by contralateral mesial structures over a much longer period. Concerning drug‐resistant localization‐related epilepsies, our results justify early consideration of surgery, especially when cortical structures are affected.
De Novo Psychogenic Nonepileptic Seizures After Epilepsy Surgery
Authors: Parra Jaime , Iriarte Jorge , Kanner Andres M. , Bergen Donna C. 
Published: August 2005

Summary: Purpose: The occurrence of de novo nonepileptic seizures (NES) after epilepsy surgery have been reported only twice in the literature (one article and one abstract). Methods: We report three patients whose de novo NES were documented by video‐EEG telemetry after epilepsy surgery. These patients were drawn from a sample of 166 consecutive patients who underwent epilepsy surgery at our center between 1989 and 1996. Results: Two patients became seizure free after surgery, and one had significant improvement of her seizures. The interval between the date of surgery and the development of the symptoms was variable (8, 10, and 47 months, respectively). The clinical phenomena of NES differed from those of the epileptic seizures preceding surgery. Their diagnosis had not been suspected in two patients before the diagnostic video‐EEG monitoring study. After the diagnosis of NES, spells stopped in two patients and recurred rarely in one. Conclusions: We conclude that de novo NES appears to occur rarely after epilepsy surgery. Given that the possibility of NES was suspected in only one patient, its incidence after surgery may be higher than so far reported. Physicians should therefore consider NES in the differential diagnosis of recurrent seizures after a seizure‐free period after epilepsy surgery.
Criteria to Assess In Vivo Performance and Bioequivalence of Generic Controlled‐Release Formulations of Carbamazepine
Authors: Bialer Meir , Yacobi Avi , Moros Daniel , Levitt Barrie , Houle Jean‐Marie , Munsaka Melvin S. 
Published: August 2005

Summary: Purpose: Concern persists that the criteria used to establish bioequivalence of generic drugs may not adequately guarantee the interchangeability of antiepileptic medications (AEDs), particularly controlled‐release (CR) formulations. We examined the utilization of several new parameters, in addition to AUC, peak plasma concentration (Cmax), and time to reach Cmax (tmax), for the assessment of bioequivalence and in vivo performance of CBZ and other CR products. These new parameters may offer additional information for evaluation of CR products that yield a prominent plateau in the plasma time‐concentration curve. They include mean residence time (MRT), Cmax/AUC, plateau time or POT (the time span associated with the concentrations within 25% of Cmax), tapical, and Capical, (the arithmetic mean of the POT times and concentrations within 25% of Cmax respectively). Additional parameters for multiple‐dose studies include the percentage fluctuation and the flatness of the steady state‐concentration curve. Methods: These proposed parameters were used in two recent (single and multiple dose) two‐way crossover studies of a new CR product of CBZ (Teril 400 CR) in comparison with Tegretol CR Divitab. Results: Teril 400 CR was found to be bioequivalent to Tegretol CR Divitab, by using both the classic and the additional proposed parameters. Both CBZ CR products have similar rates of absorption and similar flatness of their plasma time‐concentration curves as assessed by visual inspection and the proposed parameters. Conclusions: The additional parameters examined may supplement the traditional single‐point parameters, Cmax and tmax for assessment of rate of absorption and the flatness of the concentration curve. Their potential benefit and practical utility was confirmed in these two studies. Absorption‐rate assessment is important in light of concentration‐related side effects associated with CBZ therapy and the impact of fluctuations and the flatness of the CBZ plasma concentration curve on the drug efficacy and tolerability.
Cerebellar Changes in Partial Seizures: Clinical Correlations of Quantitative SPECT and MRI Analysis
Authors: Bohnen Nicolaas I. , O'Brien Terence J. , Mullan Brian P. , So Elson L. 
Published: August 2005

Summary: Purpose: To determine the frequency and patterns of periictal cerebellar hyperperfusion, whether it is associated with increased cerebellar atrophy, and whether cerebellar hyperperfusion and cerebellar atrophy are associated with predisposing clinical factors or with the outcome of epilepsy surgery. Methods: Periictal and interictal SPECT scans and volumetric brain magnetic resonance imaging (MRI) were quantitatively analyzed in 54 consecutive patients with medically refractory partial epilepsy. Their histories were reviewed and their postsurgical outcomes assessed. Results: Significant periictal cerebellar hyperperfusion was found in 26 (48.1%) patients, of whom 18 had CCH, two had homolateral cerebellar hyperperfusion (HCH), and six had symmetrical bilateral hyperperfusion (BCH). No relation found between the site of the SPECT seizure localization and the presence or type of cerebellar hyperperfusion. CCH was more common when the injected seizure involved unilateral clonic motor activity (p < 0.05). A smaller MRI relative cerebellar volume (cerebellar volume/cerebral volume) was correlated with a greater seizure frequency (Rs= ‐0.30; p < 0.05) but not with the duration of epilepsy. There was no difference in the cerebellar volumes between the different patterns of cerebellar perfusion (p > 0.05). However, patients without a focal structural MRI lesion had significantly smaller cerebellar volumes (p < 0.05). In patients who underwent epilepsy surgery (n = 31), there was a trend for those without excellent outcomes to have smaller relative cerebellar volumes than did those with excellent outcome (10.6 vs. 11.8%; p = 0.08). Conclusions: Periictal changes in cerebellar perfusion, particularly CCH, are common in patients with intractable partial epilepsy. However, periictal hyperperfusion does not appear to be a major contributor to the development of cerebellar atrophy.
Location of the Epileptic Zone and Its Physiopathological Effects on Memory‐Related Activity of the Temporal Lobe Structures: A Study with Intracranial Event‐Related Potentials
Authors: Guillem François , N'Kaoua Bernard , Rougier Alain , Claverie Bernard 
Published: August 2005

Summary: Purpose: Neuropsychological research with epileptic patients has suggested that the location of seizure focus may be an important variable determining the nature and severity of memory impairments. According to this assumption, this study was designed to investigate the effects of the location of the epileptic zone on the memory‐related activity recorded directly from different temporal lobe structures. Methods: Intracranial event‐related potentials (ERPs) were recorded during a continuous recognition memory task, which is known to elicit the modulation of N400 and P600 components (i.e., the ERP old/new effect). The patients were separated into three groups according to the location of their epileptic zone: unilateral temporal (UTE), temporal plus extra‐temporal (TEE), and bitemporal (BTE). Recordings were obtained from three temporal lobe structures: hippocampus, amygdala, and lateral temporal cortex. Results: The results showed that in the hippocampus, the ERP oldhew effect was abolished in the TEE group only. In the amygdala, although largely unaffected, the ERP modulation appeared to be more impaired in UTE patients. Contrasting with these data is the observation that the magnitude and reliability of the ERP oldnew effect recorded at the neocortical level increases as the epileptic zone extends to the temporal lobes (i.e., BTE>TEE>UTE). Conclusions: It is concluded that the memory‐related activity modulation of memory ERPs recorded from different temporal lobe structures is affected differently by the presence of an epileptic zone as a function of its location. The possible clinical implications of these findings in surgery planning are also discussed.
Risk of Epilepsy in Patients with Multiple Sclerosis: A Population‐Based Study in Iceland
Authors: Olafsson Elias , Benedikz John , Hauser W. Allen 
Published: August 2005

Summary: Purpose: Several clinical series reported an association between multiple sclerosis (MS) and epilepsy. We conducted a total population study in Iceland to determine the risk for developing epilepsy in patients with MS compared with that expected in the general population. Methods: Medical records of the 188 incidence cases of clinically definite MS first diagnosed in Iceland during the 25‐year study period (1965–1989) were reviewed. The cases were followed up through 1994 or until death to identify those developing seizures or epilepsy. The expected number of cases with epilepsy in the MS‐incidence cohort were calculated based on the age‐specific incidence for epilepsy in Iceland and the age‐specific person years of follow‐up in the MS cohort. Results: During the 2,771 person years of observation after diagnosis of clinically definite MS, three MS patients developed epilepsy. One additional case developed epilepsy after onset of MS symptoms but before diagnosis of MS. The cumulative incidence of epilepsy by 10 years after diagnosis of MS was 1.9%. Given the age‐specific person years of follow‐up after diagnosis of MS, only one case of epilepsy would have been expected; standardized incidence ratio (SIR), 3.0 (95% confidence interval (CI), 0.6–8.8). Conclusions: MS is a risk factor for developing epilepsy. Patients with MS have a threefold increase in risk for developing epilepsy when compared with that expected in the general population. The reason for this increased risk is unclear and needs further investigation.