bluuebunny/crossref_metadata_2025_split huggingface dataset:
Buccal Absorption of Midazolam: Pharmacokinetics and EEG Pharmacodynamics
Authors: Scott Rod C. , Besag Frank M. C. , Boyd Stewart G. , Berry David , Neville Brian G. R. 
Published: August 2005

Summary: Purpose: To determine whether buccal/sublingual administration of midazolam (MDL) would lead to detectable venous concentrations and EEG changes in 10 healthy volunteers. Methods: The study consisted of an open‐label and a double‐blind phases. Subjects held 10 mg MDL in 2 ml peppermint‐flavored fluid or peppermint‐flavored placebo in their mouth for 5 min and then spat it out. Cardiorespiratory and EEG monitoring was performed in all subjects. Results: Venous MDL concentrations measured on 10 occasions from 5 to 600 min after administration showed a rapid increase for the first 20–30 min. However, changes in the 8‐to 30‐Hz frequencies identified by spectral analysis of the EEG showed changes in ≤5–10 min in test but not in control subjects—more rapid than were expected from the venous absorption data. There were no significant adverse effects. Conclusions: Our data provide direct evidence of the speed of cerebral effect of a drug. Our results suggest that the buccal/sublingual route of administration should be tested in emergency treatment of seizures as an alternative to the rectal route, over which it has clear practical advantages.
Brain Hypometabolism in a Model of Chronic Focal Epilepsy in Rat Neocortex
Authors: Hagemann Georg , Bruehl Clam , Lutzenburg Michael , Witte Otto W. 
Published: August 2005

Summary: Purpose: Metabolic mapping of the human brain has become a widely used method for identifying and localizing epileptic foci. A reduction of glucose consumption usually is found interictally in the area of the focus. By contrast, animal models of acute epilepsy show a hypermetabolism in the epileptic focus. Here we investigated how metabolism is altered in an animal model of chronic epilepsy caused by focal injection of tetanus toxin into rat neocortex. Methods: A total of 27 male Wistar rats were anesthetized and injected into the motor or sensory cortex either with dissolved tetanus toxin or with the solvent only. Animals recovered for 7, 14, or 30 days and then were anesthetized again for quantitative 14C–deoxyglucose autoradiography. Data were analyzed with an imaging program, and regional cerebral glucose metabolism (rCMRGlc) was determined. Results: Injection of tetanus toxin into the motor cortex caused a focal hypometabolism which was confined to the cytoarchitectonic boundaries of the injected area, whereas sensory cortex injection caused a more widespread hypometabolism in all sensory cortical and connected, areas. None of the animals displayed focal hypermetabolism and we observed no significant time–dependent alteration of brain metabolism. Conclusions: Tetanus toxin injection into the cortex of the rat induces chronic epileptic activity accompanied by a focal hypometabolism. The data suggest that the spread of the metabolic alterations depends on the connectivity of the injected cortical area.
Psychiatric Outcome of Temporal Lobectomy for Epilepsy: Incidence and Treatment of Psychiatric Complications
Authors: Blumer Dietrich , Wakhlu Sidarth , Davies Keith , Hermann Bruce 
Published: August 2005

Summary: Purpose: To determine the incidence of psychiatric disorders before and after surgical treatment for partial epilepsy and to document the effectiveness of their treatment. Methods: Fifty consecutive patients treated surgically for focal epilepsy (44 temporal and six frontal) were evaluated by established neuropsychiatric methods before surgery and over a mean period of 2 years after surgery. The patients with interictal dysphoric disorders, with or without psychotic episodes, were treated with tricyclic antidepressant medication alone or combined with serotonin selective reuptake inhibitors and, if necessary, with the addition of risperidone. Results: Before surgery, 25 (57%) of the 44 patients with temporal lobe epilepsy had dysphoric disorders. After surgery, 17 (39%) of the 44 patients experienced either de novo psychiatric complications (six psychotic episodes, six dysphoric disorders, and two depressive episodes) or exacerbation of preoperative dysphoric disorder (three patients). Eight previously intact patients of the 19 (42%) developed dysphoric disorders after surgery that were significantly related to recurrence of seizures. All psychiatric complications occurred in the first 2 months after surgery, except for the six patients intact before surgery, who had a recurrence of seizures. A significant predictor of ultimate excellent psychiatric outcome was complete absence of seizures after surgery. All postoperative psychiatric complications remitted on treatment with psychotropic medication in the compliant patients. Conclusions: An exceptional psychiatric morbidity is associated with the months after temporal lobectomy. Possible pathogenetic mechanisms are discussed. Antidepressant drugs are very effective in treating the psychiatric disorders of chronic epilepsy; their use in conjunction with the surgical treatment of epilepsy appears to be crucial for the overall positive outcome of a significant number of patients.
Lamotrigine Hypersensitivity in Childhood Epilepsy
Authors: Iannetti Paola , Raucci Umberto , Zuccaro Piergiorgio , Pacifici Roberta 
Published: August 2005

Summary: Purpose: To evaluate the effect of lamotrigine (LTG) on several humoral and cellular immune functions in children with epilepsy and the change in immunological status in patients with LTG‐induced rash. Methods: Sixteen children with epilepsy of unknown origin or secondary to various etiologies undergoing treatment with LTG participated in the humoral and cellular immunological study. Of these, 2 patients developed a rash during LTG treatment and are described in detail. Results: No modifications of humoral or cellular immunity (measured at 1 and 3 months) were noted in 14 of the 16 patients during this treatment. In the 2 children who manifested rash, basal immune function was normal. In both, immediately after the skin rash appeared, there was a high increase in the percentage of activated T‐helper lymphocytes (CDCDR) and activated T‐suppressor lymphocytes (CDS‐DR), a slight increase in percentage of B lymphocytes (CD19), and a greater increase in serum concentration of IgE. In 1 of the 2 patients, reevaluation of immunity 20 days after the rash appeared and after LTG suspension showed normal percentages of CDCDR, CDS‐DR, and CD19, whereas the serum concentration of IgE had decreased. Conclusions: The observed immunological results indicate that LTG‐induced rash may be considered an immune‐mediated hypersensitivity reaction.
Semiological Seizure Classification*
Authors: Lüders H. , Acharya J. , Baumgartner C. , Benbadis S. , Bleasel A. , Burgess R. , Dinner D. S. , Ebner A. , Foldvary N. , Geller E. , Hamer H. , Holthausen H. , Kotagal P. , Morris H. , Meencke H. J. , Noachtar S. , Rosenow F. , Sakamoto A. , Steinhoff B. J. , Tuxhorn I. , Wyllie E. 
Published: August 2005

Summary: We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows:a. Auras are ictal manifestations having sensory, psychosensory, and experiential symptoms.b. Autonomic seizures are seizures in which the main ictal manifestations are objectively documented autonomic alterations.c. “Dialeptic” seizures have as their main ictal manifestations an alteration of consciousness that is independent of ictal EEG manifestations. The new term “dialeptic” seizure has been coined to differentiate this concept from absence seizures (dialeptic seizures with a generalized ictal EEG) and complex partial seizures (dialeptic seizures with a focal ictal EEG).d. Motor seizures are characterized mainly by motor symptoms and are subclassified as simple or complex. Simple motor seizures are characterized by simple, unnatural movements that can be elicited by electrical stimulation of the primary and supplementary motor area (myoclonic, tonic, clonic and tonic‐clonic, versive). Complex motor seizures are characterized by complex motor movements that resemble natural movements but that occur in an inappropriate setting (“automatisms”).e. Special seizures include seizures characterized by “negative” features (atonic, astatic, hypomotor, akinetic, and aphasic seizures).The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed.
Magnetoencephalography in Presurgical Evaluation of Children with the Landau‐Kleffner Syndrome
Authors: Paetau Ritva , Granström Marja‐Liisa , Blomstedt Göran , Jousmäki Veikko , Korkman Marit , Liukkonen Elina 
Published: August 2005

Summary: Purpose: Our aim was (a) to localize the primary epileptogenic cortex for possible multiple subpial transsection in four children with the Landau‐Kleffner syndrome (LKS), and (b) to evaluate the impact of magnetoencephalography (MEG) in the localizing process. Methods: We used EEG to detect the overall epileptiform activity and MEG for selective recording of fissural spikes. The cortical generators of MEG spikes were modeled with dipoles, and their activation order was determined. The voltage distribution, consistent with the earliest MEG sources, was then identified during the course of the patient's EEG spikes to determine the relative timing between stereotypic EEG and MEG spikes and to distinguish the earliest (primary) source area among the secondary ones. Results: In all patients, the earliest spike activity originated in the intrasylvian cortex, spreading in one subject to the contralateral sylvian cortex within 20 ms. Secondary spikes occurred within 10–60 ms in ipsilateral perisylvian, temporooccipital, and parietooccipital areas. A single intrasylvian pacemaker initiated all epileptic activity in two patients, whereas the other two had independent left‐ and right‐hemisphere circuits or focal spikes. MEG source dynamics predicted the results of the methohexital suppression test in two patients and was confirmed by surgery outcome in one patient, in whom all epileptic activity ceased after a small transsection of the sylvian pacemaker. Conclusions: (a) The intrasylvian cortex is a likely pacemaker of epileptic discharges in LKS, and (b) MEG provides useful presurgical information of the cortical spike dynamics in LKS patients.
Effects of Age and Gender on Single‐Dose Pharmacokinetics of Gabapentin
Authors: Boyd Rebecca A. , Türck Dietrich , Abel Robert B. , Sedman Allen J. , Bockbrader Howard N. 
Published: August 2005

Summary: Purpose: This study was conducted to evaluate the effect of age, age‐related changes in renal function, and gender on the single‐dose pharmacokinetics of orally administered gabapentin (GBP). Methods: The pharmacokinetics of a single 400‐mg oral dose of GBP were studied in 36 healthy subjects (18 men and 18 women) aged 20–78 years. Serial blood samples and total urine output were collected for 48 h after the dose. GBP concentrations in plasma and urine were measured by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental methods. Results: All subjects tolerated the drug well, with only mild symptoms reported. No change in maximal GBP plasma concentration (Cmax), time at which Cmax occurred (tmax), or apparent volume of distribution (V/F) with age was noted. A significant linear decline in apparent oral clearance (CL/F), elimination‐rate constant (λz), and renal clearance (CLR) with increasing age was observed (p < 0.005). Because total urinary recovery of unchanged drug (an estimate of F for GBP) did not change with age, the decline in CL/F and λz can be explained by the decline in CLR. The only pharmacokinetic parameter that was significantly different between genders was Cmax, which was −25% higher for women than for men (p = 0.016), consistent with gender differences in body size. Conclusions: The results of this study suggest that changes in renal function are responsible for age‐related changes in GBP pharmacokinetics. Reduction of GBP dosage may be required in elderly patients with reduced renal function. The pharmacokinetics of GBP are similar in men and women.
Increased High‐Density Lipoprotein Cholesterol in Patients with Epilepsy Treated with Carbamazepine: A Gender‐Related Study
Authors: Sudhop T. , Bauer J. , Elger C. E. , von Bergmann K. 
Published: August 2005

Summary: Purpose: Long‐term treatment with carbamazepine (CBZ) may alter serum lipoprotein concentrations. Gender‐related examinations, however, are rare and inconsistent in their results. Methods: To examine possible sex differences, serum lipo‐proteins were analyzed in 127 clinic outpatients (56 women and 71 men) with epilepsies with focal or secondarily generalized tonic‐clonic seizures (or both) treated with a CBZ mono‐therapy. Results were compared with a control group of 177 blood donors (67 women and 110 men) matched for age and weight. Results: Total cholesterol, low‐density lipoprotein (LDL) cholesterol and high‐density lipoprotein (HDL) cholesterol were higher in both male and female patients treated with CBZ compared with controls. The known sex difference in serum lipoprotein concentrations (i.e., higher LDL cholesterol and triglycerides but lower HDL cholesterol in men) was confirmed in controls and patients treated with CBZ, with the exception of LDL cholesterol. The HDL as well as the LDL differences were significantly more pronounced in women treated with CBZ than in men when compared with their controls. These results were independent of the dose of CBZ and plasma concentrations. Lathosterol, a cholesterol precursor, and its ratio to cholesterol, an indicator of cholesterol synthesis, were not different, when compared between gender and different HDL groups. Conclusions: The observed increase in HDL cholesterol in patients with CBZ, especially in women, might correlate with the previously reported diminished rate of death from coronary heart disease in patients with epilepsy as HDL exerts an anti‐atherogenic effect.
Incidence of Death in Patients with Intractable Epilepsy During Nitrazepam Treatment
Authors: Rintahaka Pertti J. , Nakagawa Jo Anne , Shewmon D. Alan , Kyyronen Pentti , Shields W. Donald 
Published: August 2005

Summary: Purpose: Increased risk of death has been reported in patients with intractable epilepsy (IE) taking nitrazepam (NZP). Methods: Between January 1983 and March 1994, 302 patients with IE were entered into a NZP compassionate‐plea protocol. NZP was discontinued if there was <50% seizure reduction or significant side effects. In some patients with >50% reduction, it also was discontinued for lack of sufficient effect. At the end of follow‐up for this study, 62 patients remained taking NZP. Patients took NZP from 3 days to 10 years. Results: Twenty‐one of 302 patients died after institution of NZP. Fourteen of 21 of these were taking NZP at death, and in five of 21, the NZP had been discontinued. Two patients were excluded from analysis, because it is unclear whether NZP had been discontinued before death. Six other patients were lost from follow‐up. Of the 14 deaths with NZP, seven were sudden, six were of pneumonia, and one was of cystinosis. Nine had at least one contributing factor, such as dysphagia, gastro‐esophageal reflux, or recurrent aspirations. The 294 patients took NZP for a total of 704 patient years (ptyrs), and were discontinued for a total of 856 ptyrs. There were 1.98 deaths/100 ptyrs on NZP compared with 0.58 deaths/100 ptyrs without NZP, most of the former being associated with side effects of NZP. Mortality in patients younger than 3.4 years was 3.98 with NZP compared with 0.26 deaths/100 ptyrs without NZP (p = 0.0002). Corresponding figures in patients 3.4 years or older were 0.50 and 0.86 deaths/100 ptyrs, respectively. Conclusions: NZP therapy for epilepsy apparently increases the risk of death, especially in young patients with IE. This should be considered in antiepileptic drug (AED) management decisions.
Role of the Midline Brainstem in Feline Amygdaloid Kindling
Authors: Wada Juhn A. , Hamada Koichi 
Published: August 2005

Summary: Purpose: To study the role played by the midline brainstem in feline amygdaloid kindling in general and the formation of transhemispheric positive transfer effect (PTE) in particular. Methods: Eight adult male cats with either anterior or posterior midline brainstem bisection underwent primary and secondary site kindling and primary site retest. Results: Stage 4 seizure pattern was altered with either absence of contralateral circling in the anterior group or emergence of ipsilateral circling in the posterior group. Electroclinical manifestation of the tonic phase was absent in the posterior but not the anterior group. Kindled convulsive pattern remained asymmetrical with contralateral dominance in the anterior but not the posterior group. Intermittent truncation of the secondary clonic phase of the kindled seizure occurred in both groups. PTE was reduced whereas the negative transfer effect was preserved in both groups. Conclusions: The anterior half of the midline brainstem participates in stage 4 contralateral circling. Both the anterior and posterior halves of the midline brainstem participate in the mechanisms of repetitive circling during stage 4 and the stable maintenance of the kindled stage 6 seizure. The anterior and posterior halves of the midline brainstem participate in symmetrical patterning and electroclinical tonic expression of the kindled seizure, respectively. The midline brainstem, extending from the midbrain to the pons with some posterior emphasis, participates in the mechanisms of PTE formation. The findings indicate the importance of the brainstem for electroclinical ictal processes and a transhemispheric positive transfer effect associated with temporal limbic epileptogenesis.
Localization of the Epileptogenic Zone by Ictal and Interictal SPECT with 99mTc‐Ethyl Cysteinate Dimer in Patients with Medically Refractory Epilepsy
Authors: Oliveira Andréa J. , da Costa Jaderson C. , Hilário Lisiane N. , Anselmi O. Estrela , Palmini André 
Published: August 2005

Summary: Purpose: To evaluate the accuracy, feasibility and clinical value of both ictal and interictal 99mTc‐ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with medically refractory epilepsy. Methods: The study included 75 consecutive patients, 48 with temporal lobe epilepsy (TLE group), and 27 with extra‐temporal epilepsy (ExT group). The accuracy of SPECT was analyzed considering the final diagnosis reached by convergence of clinical, electrophysiologic, structural, pathologic and outcome data. Results: Ictal SPECT correctly identified the epileptogenic zone in 21 (91.3%) of 23 patients, whereas interictal SPECTs could correctly identify the epileptogenic zone in only 41 (62.1%) of 66 patients (χ2= 5.56, df = 1, p < 0.05). Results were similar when the two study groups were analyzed separately. Moreover, ictal studies had significantly higher specificity (91.3 vs. 60.6%) and positive predictive value (91.3 vs. 66.2%) than interictal studies for the whole series of patients. Considering all tools used in the preoperative workup of these patients, ictal SPECT significantly contributed to the final topographic diagnosis in seven of 14 patients from TLE group and in six of nine patients from the ExT group. In these patients, ictal SPECT either obviated the need for invasive EEG or helped to define where to concentrate the efforts of invasive investigation. Conclusions: These data demonstrate that ictal SPECT can be easily achieved by using 99mTc‐ECD and can accurately localize the epileptogenic zone in both temporal and extratemporal epilepsies. Ictal ECD SPECT proved to be significantly more sensitive and specific than interictal ECD SPECT, and clinically useful in the definition of the epileptogenic zone.
Epilepsy and EEG Findings in Males with Fragile X Syndrome
Authors: Musumeci S. A. , Hagerman R. J. , Ferri R. , Bosco P. , Bernardina B. Dalla , Tassinari C. A. , De Sarro G. B. , Elia M. 
Published: August 2005

Summary: Purpose and Methods: One hundred and ninety‐two fragile X male patients were investigated for seizures and EEG findings, 168 in a retrospective and 24 in another prospective study, to characterize the natural history of seizures, epilepsy, and EEG abnormalities in males with this syndrome. Results: Seizures were documented in 35 (18.2%) of 192 patients; they never started before the age of 2 years or after the age of 9 years. Seizures were frequently of the complex partial type and less frequently of the partial motor and generalized type. Seizures involving frontal and temporal lobes were commonly seen and were usually well controlled by anticonvulsants. In the majority of young fragile X patients studied, an age‐related paroxysmal EEG pattern was found, which showed neurophysiologic characteristics very similar to those of the centrotemporal spikes. Conclusions: These findings confirm that fragile X syndrome can be considered a genetic model of epilepsy.
Development of the Quality of Life in Epilepsy Inventory for Adolescents: The QOLIE‐AD‐48
Authors: Cramer Joyce A. , Westbrook Lauren E. , Devinsky Orrin , Perrine Kenneth , Glassman Marc B. , Camfield Carol 
Published: August 2005

Summary: Purpose: We report the development of an instrument to assess health‐related quality of life (HRQOL) in adolescents with epilepsy. Methods: A sample of 197 English‐speaking adolescents (aged 11–17 years) with epilepsy completed a test questionnaire of 88 items. Also included were mastery and self‐esteem scales to assess external validity. A parent simultaneously completed an 11‐item questionnaire to evaluate the child's HRQOL. Both adolescent and parent questionnaires were repeated in 2–4 weeks. Demographic information and information pertaining to seizures were collected at baseline along with assessment of systemic and neurologic toxicity. Results: The QOLIE‐AD‐48 contains 48 items in eight subscales: epilepsy impact (12 items), memory/concentration (10), attitudes toward epilepsy (four), physical functioning (five), stigma (six), social support (four), school behavior (four), health perceptions (three), and a total summary score, with higher scores indicating better HRQOL. Internal construct validity was demonstrated in a single‐factor solution for the eight dimensions. All correlations were statistically significant at p < 0.05 level. Internal consistency reliability estimated by Cronbach's alpha coefficient was 0.74 for the summary score and ranged from a low of 0.52 (three‐item Health Perceptions Scale) to 0.73–0.94 for the other individual scales. Good testretest reliability was found for the overall measure (0.83). Summary score correlations with the two external validity scales, self‐efficacy and self‐esteem were 0.65 and 0.54, respectively. Statistically significant differences in summary scores indicating that HRQOL was increasingly better for adolescents as seizure severity decreases (no seizures = 77 ± 13, low = 70 ± 17, high = 63 ± 17) were found among seizure‐severity groups. Conclusions: These data describe the development of a robust instrument to evaluate HRQOL in adolescents with epilepsy. Empiric analyses provide strong evidence that the QOLIE‐AD‐48 is both a reliable and valid measure for adolescents with epilepsy.