bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Benign Idiopathic Partial Epilepsy and Brain Lesion
Authors: Stephani U. , Doose H.
Published: August 2005

Summary: A 14‐year‐old girl had severe head trauma from a dog bite at the age of 9 days. This resulted in extensive brain damage, tetraplegia, mental retardation, and epilepsy. The seizures were of rolandic type, and the EEG showed multifocal sharp waves. The course was benign. The initial diagnosis of a pure symptomatic epilepsy was revised after demonstrating typical benign focal sharp waves in the EEG of the healthy sister. Thus a phenocopy of a benign partial epilepsy by the brain lesion could be excluded with sufficient certainty. This observation allows the conclusion that the genetic disposition underlying the sharp‐wave trait characteristic of benign partial epilepsies can be involved also in the pathogenesis of seemingly pure symptomatic epilepsies. EEG studies on siblings of such patients are needed to exclude possible phenocopies.
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.
Topiramate and Metabolic Acidosis
Authors: Wilner Andrew , Raymond Kent , Pollard Richard
Published: August 2005

Summary: Topiramate (TPM) is a novel antiepileptic medication (AED) with at least three mechanisms of action. A possible fourth mechanism, that of a carbonic anhydrase inhibitor, also may contribute to its antiepileptic properties. We report a patient with intractable epilepsy and normal renal function who developed a normal anion gap metabolic acidosis, which worsened during elective surgery for temporal lobectomy. We believe this side effect of TPM can become clinically significant during surgery, concomitant use of another carbonic anhydrase inhibitor, and potentially with the ketogenic diet.
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.
Effects of Incorporating Memory Confidence Ratings and Language Handicap Modifications on Intracarotid Amobarbital Procedure (Wada Test) Memory Asymmetry Scores
Authors: Hamberger Marla J. , Hirsch Lawrence J.
Published: August 2005

Summary: Purpose: Intracarotid amobarbital procedure (IAP) memory asymmetry scores are often considered in determining lateralization of temporal lobe seizure foci. Additionally, these scores sometimes influence treatment plans for epilepsy surgery candidates. We examined the effects of two scoring modifications on IAP asymmetry scores: incorporating memory confidence ratings (MC), and use of a language handicap (LH) (i.e., adding a point to the memory score with anesthetization of the language‐dominant hemisphere), both of which could be applied to most IAP protocols despite variations in testing methods among epilepsy surgery programs.

Methods: Sixty‐nine consecutive unilateral temporal lobe epilepsy (TLE) patients with subsequent good surgical outcomes (Engel I or II) underwent bilateral IAP testing. Confidence ratings were obtained for all memory responses. The incorporation of confidence ratings and the application of a language handicap for dominant‐hemisphere injections were applied to memory asymmetry scores in all combinations, resulting in four scoring methods. Results of the four methods were compared with respect to the proportion of patients lateralized accurately by each method.

Results: No patients were falsely lateralized with any method. Percentage of patients correctly lateralized with each scoring method is shown in Table 2. The results obtained with MC and with MC + LH (67% and 64% of patients accurately lateralized, respectively) were significantly better than results obtained with LH (55%, p < 0.05). No other differences were significant.

Conclusions: Although not statistically superior to standard methods, these results suggest that incorporating memory confidence ratings into IAP protocols may increase the likelihood of obtaining asymmetry scores that accurately lateralize to the hemisphere of seizure onset. In contrast, inclusion of a language handicap for scores obtained with the languagedominant ICA injection were not helpful and may even decrease the probability of obtaining clinically useful lateralizing data. These scoring modifications can be applied to most IAP protocols.
Emotion‐Induced Myoclonic Absence‐Like Seizures in a Patient with Inv‐Dup(15) Syndrome: A Clinical, EEG, and Molecular Genetic Study
Authors: Aguglia Umberto , Le Piane Emilio , Gambardella Antonio , Messina Demetrio , Russo Concetta , Sirchia Silvia Maria , Porta Giovanni , Quattrone Aldo
Published: August 2005

Summary: We have described a clinical EEG and molecular genetic study of a 9‐year‐old boy with inv‐dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5–20 s after the onset of repeated cheek‐kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence‐like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11‐q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral γ‐aminobutyric acid (GABA)‐mediated inhibition accounts for the severe epilepsy that we observed in this patient.
Photic Reflex Myoclonus: A Neurophysiological Study in Progressive Myoclonus Epilepsies
Authors: Rubboli Guido , Meletti Stefano , Gardella Elena , Zaniboni Anna , D'Orsi Giuseppe , Dravet Charlotte , Tassinari Carlo Alberto
Published: August 2005

Purpose: To investigate the neurophysiological features of photic reflex myoclonus (PRM) in patients with progressive myoclonus epilepsies (PMEs) of different types (Unverricht‐Lundborg disease, Lafora's disease, cryptogenic).

Methods: All patients underwent computerized video‐polygraphic recordings, collecting electromyographic (EMG) activity from several cranial and limb muscles. PRM was elicited by intermittent photic stimulation (IPS).

Results: IPS could evoke PRM with a 1:1 relation at frequencies up to 12 Hz. Back‐average of the EEG, triggered from the onset of PRM at the upper limbs, showed a contralateral positive‐negative transient in central region, preceded by ∼10 ms by a similar, ipsilateral occipital wave. When IPS induced bilateral jerking, a time lag of ∼10 ms between the homologous muscles of the two sides was observed, paralleled by a similar delay between the associated contralateral EEG transients in the two central regions, suggesting spread of cortical myoclonic activity from one hemisphere to the other via transcallosal fibers. PRM propagated in different cranial and limb muscles according to a rostrocaudal pattern, with latencies compatible with a transmission along fast‐conducting corticospinal motor pathways.

Conclusions: In our PME patients, PRM presented uniform neurophysiological features, indicating the participation of both occipital and motor cortices, with bilateral spread presumably mediated by transcallosal connections and propagation down the spinal cord via fast‐conducting corticospinal pathways.
Seizures During Video‐Game Play and Other Common Leisure Pursuits in Known Epilepsy Patients Without Visual Sensitivity
Authors: Millett C. J. , Fish D. R. , Thompson P. J. , Johnson A.
Published: August 2005

Purpose: Some individuals who are negative to flash/pattern sensitivity have been reported to experience seizures while exposed to video games. This study seeks to examine systematically whether exposure to video‐game material is a risk factor for seizures in patients with chronic epilepsy without visual sensitivity.

Methods: Two hundred and twelve chronic epilepsy patients participated in the study. All were negative to rigorous flash and pattern sensitivity testing. They were randomly allocated to a video game‐playing session or to a period of leisure (involving reading, physical exercise, puzzles, etc.) and then alternated between these activities for a fixed total of eight 45‐min periods while undergoing video‐EEG monitoring. The study ceased if the participant experienced a clinical seizure.

Results: Twenty‐five of 212 subjects experienced a seizure while participating in the study. Thirteen seizures occurred during periods of video‐game play, and 12 during alternative leisure.

Conclusions: We have not identified a greater risk of seizures in patients with (not visually sensitive) epilepsy during videogame play compared with other common leisure pursuits. Furthermore, we exposed a large population (212 patients) mostly with severe epilepsy, mainly drug reduced and some sleep deprived, to prolonged video game‐playing without observing a significant excess number of seizures. This finding provides strong support for the hypothesis that seizures during video game play in the >95% of the epilepsy population without visual sensitivity are most likely to represent a chance occurrence, although, as always, each individual should be carefully assessed.
Zonisamide
Authors: Leppik Ilo E.
Published: August 2005

Zonisamide (ZNS) is a broad‐spectrum antiepileptic drug in both animal models of epilepsy and patients with epilepsy. It is effective for both localization‐related and generalized epilepsies and appears to be particularly potent in progressive myoclonic epilepsy syndromes. Its pharmokinetic profile is favorable, with a long half‐life and low protein binding. However, its insolubility may make the development of a parenteral formulation difficult. Its safety profile is good, although teratogenicity in animal models is of concern. Adult doses of 400–600 mg per day in two doses, with blood levels from 20 to 30 mg/ml, appear to be effective.
Topiramate
Authors: Glauser Tracy A.
Published: August 2005

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial‐onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial‐onset seizures in children, tonic‐clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox‐Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.
Increased Sensitivity to Seizures in Mice Lacking Cellular Prion Protein
Authors: Walz Roger , Amaral Olavo B. , Rockenbach Isabel C. , Roesler Rafael , Izquierdo Iván , Cavalheiro Esper A. , Martins Vilma R. , Brentani Ricardo R.
Published: August 2005

Summary: Purpose: The physiologic role of the cellular prion protein (PrPc) is unknown. Mice devoid of PrPc develop normally and show only minor deficits. However, electrophysiologic and histologic alterations found in these mice suggest a possible role for PrPc in seizure threshold and/or epilepsy.

Methods: We tested the sensitivity of PrPc knockout mice to seizures induced by single convulsant or repeated subconvulsant (kindling) doses of pentylenetetrazol (PTZ), and to status epilepticus (SE) induced by kainic acid or pilocarpine.

Results: In PTZ kindling, seizure severity progressed faster in the PrPc knockout group, in which 92.8% reached stage 5 or death after 4 days of stimulation, as opposed to 38.4% in wild‐type animals. After 10 injections, mortality was 85.7% among knockouts and 15.3% among controls. After a single PTZ injection (60 mg/kg), overall mortality due to seizures was 91% in knockout mice, but only 33% among wild‐type animals. Pilocarpine‐induced SE (320 mg/kg) caused an 86.7% mortality in knockouts, as opposed to 40% in wild‐type animals. Finally, after kainic acid injections (10 mg/kg), 70% of the knockouts developed at least one severe seizure, and 50% showed repetitive seizures, whereas no wild‐type animal exhibited observable seizures.

Conclusions: Animals lacking cellular prion protein expression are more susceptible to seizures induced by various convulsant agents. This is perhaps the most striking alteration yet found in PrPc‐null mice, who at first analysis appeared to be completely normal. A possible role for PrPc in chronic and idiopathic (familial), secondary, or cryptogenic epilepsies in humans remains to be investigated.
Apolipoprotein E Polymorphisms and the Risk of Nonlesional Temporal Lobe Epilepsy
Authors: Gambardella Antonio , Aguglia Umberto , Cittadella Rita , Romeo Nelide , Sibilia Grazia , LePiane Emilio , Messina Demetrio , Manna Ida , Oliveri Rosario L. , Zappia Mario , Quattrone Aldo
Published: August 2005

Summary: Purpose: To evaluate whether the inheritance of the apolipoprotein E (ApoE) ε4 allele is a risk factor for nonlesional temporal lobe epilepsy (TLE), and to determine whether the newly described ‐491 A/T ApoE polymorphism may independently affect the risk of nonlesional TLE.

Methods: The study group consisted of 63 patients (35 women and 28 men; age at onset of epilepsy, 30.6 ± 19.6 years; mean (±SD). All of them had received a diagnosis of nonlesional TLE after a detailed clinical, electroencephalographic, and brain magnetic resonance investigation. The ApoE polymorphisms were determined from blood samples by standard methods. The molecular study also was performed in 220 age‐ and sex‐matched normal individuals.

Results: There were no differences between TLE patients and controls in either allelic or genotypic frequencies of the ApoE and ‐491 A/T polymorphisms. Moreover, no effect of ApoE or ‐491 A/T polymorphisms was found on the age at onset and severity of epilepsy.

Conclusions: The allelic and genotypic frequencies of ApoE polymorphisms in Italian patients with nonlesional TLE are comparable to control values, indicating that ApoE polymorphisms are not a significant genetic risk factor for the occurrence of nonlesional TLE.
Improvement and Deterioration of Seizure Control During the Postsurgical Course of Epilepsy Surgery Patients
Authors: Ficker D. M. , So E. L. , Mosewich R. K. , Radhakrishnan K. , Cascino G. D. , Sharbrough F. W.
Published: August 2005

Summary: Purpose: To determine the factors associated with changes in seizure control during the postsurgical course of epilepsy surgery patients.

Methods: Evaluation of patients after consecutive temporal and frontal resection whose seizure frequency was scored for each year of postsurgical follow‐up. In each cohort, patients with a change in their seizure control after the first postsurgical year were compared with control subjects to determine factors that may be responsible for the change.

Results: Thirty‐three (15%) of 214 temporal lobectomy versus 12 (20%) of 59 frontal resection patients experienced a change in seizure control (p < 0.05). Ten (5%) of 214 temporal lobectomy versus nine (15%) of 59 frontal resection patients experienced an improvement in seizure control (p = 0.009), but 23 (11%) of 214 temporal lobectomy versus three (5%) of 59 frontal resection patients had a worsening in seizure control (p < 0.05). In temporal lobectomy patients, preoperative unilateral temporal epileptiform discharges were associated with improvement (p = 0.03), whereas older age at surgery was associated with worsening of seizure control (p = 0.007). In frontal resection patients, presence of a congenital central nervous system (CNS) anomaly was associated with late improvement in seizure control (p = 0.006).

Conclusion: During the postsurgical course, an improvement in seizure control is more common after frontal resection than after temporal lobectomy. Factors associated with improvement are the presence of a congenital CNS abnormality in frontal resection patients, and the occurrence of preoperative unilateral epileptiform discharges in temporal lobectomy patients. Older age at temporal lobectomy may be associated with greater risk of worsening seizure control.
Psychosis After Resection of Ganglioglioma or DNET: Evidence for an Association
Authors: Andermann Lisa F. , Savard Ghislaine , Meencke Heinz Joachim , McLachlan Richard , Moshé Solomon , Andermann Frederick
Published: August 2005

Summary: Purpose: David Taylor and Murray Falconer suggested that some patients may develop a psychotic illness after resection of a ganglioglioma that led to intractable seizures. They implied that the mechanism of this association remained unclear. This concept is currently not universally accepted (M. Trimble, personal communication).

Methods: We studied six children or young adults from four centers who developed psychosis after resection of a ganglioglioma or dysembryoplastic neuroepithelioma (DNET).

Results: All patients were operated on because of intractable epilepsy. The lesions involved mainly the temporal lobe. Patients had good outcomes for seizure control. In none of the six was potentially psychogenic medication used nor were the psychotic symptoms postictal in nature. The psychosis was schizophreniform with paranoid features and prominent depressive symptoms. Although some behavioral abnormalities were described preoperatively, none had been psychotic before operation. This type of psychotic reaction was not encountered in the four centers in a comparable period after resection of other types of lesions. This complication is rare; it occurred in only one of 39 patients who had such a lesion resected.

Conclusions: Psychotic illness may rarely occur after resection of a ganglioglioma or DNET for treatment of intractable epilepsy. This does not seem to occur after removal of other types of lesions. Because the patients had good outcomes for seizures, the mechanism may be related to “forced normalization.” The original observations of Taylor and Falconer are confirmed by this study; the reasons for the selective occurrence, however, remain speculative.
Recent Advances in the Genetics of Epilepsy: Insights from Human and Animal Studies
Authors: Prasad Asuri N. , Prasad Chitra , Stafstrom Carl E.
Published: August 2005

Summary:Progress in understanding the genetics of epilepsy is proceeding at a dizzying pace. Due in large part to rapid progress in molecular genetics, gene defects underlying many of the inherited epilepsies have been mapped, and several more are likely to be added each year. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, and correlate these advances with rapidly expanding information about the mechanisms of epilepsy gained from both spontaneous and transgenic animal models. We also provide practical suggestions for clinicians confronted with families in which multiple members are afflicted with epilepsy.
Short‐Term Mortality After a First Epileptic Seizure: A Population‐Based Study
Authors: Loiseau Jérôme , Picot Marie‐Christine , Loiseau Pierre
Published: August 2005

Summary: Purpose: To determine the short‐term mortality in a prospective incidence cohort of patients included after any kind of first afebrile epileptic seizure (i.e., provoked and unprovoked).

Methods: Information on death occurring within the first year of follow‐up was collected in a cohort of 804 patients with a first seizure between March 1, 1984, and February 28, 1985, in southwest France. The variables analyzed were the etiology of seizure, cause of death, interval between seizure and death, and age of patients.

Results: By the end of the 1‐year follow‐up, there were 149 deaths among these patients as compared with 16 expected deaths [standardized mortality ratio (SMR), 9.3; 95% confidence interval (CI), 7.9–10.9]. There were no deaths in patients with idiopathic seizures. Patients with cryptogenic seizures had slightly increased mortality (SMR, 1.6; 95% CI, 0.4–4.1). Mortality was increased for patients with remote symptomatic seizures (SMR, 6.5; 95% CI, 3.8–10.5), provoked seizures (SMR, 10.1; 95% CI, 8.1–12.4), and seizures due to a progressive neurologic condition (SMR, 19.8; 95% CI, 14.0–27.3). Causes of death were underlying pathology (64%), unrelated condition (20%), unknown cause (9%), seizure‐related death (6%), and one suicide.

Conclusions: Early mortality clearly differed according to the etiology of the first seizure. The highest mortality was associated with provoked seizures and with seizures caused by progressive central nervous system disorders. Patients died far more often from underlying or unrelated conditions than from seizures.
Correlations Between Granule Cell Dispersion, Mossy Fiber Sprouting, and Hippocampal Cell Loss in Temporal Lobe Epilepsy
Authors: Bahh Bouchaib El , Lespinet Véronique , Lurton Dominique , Coussemacq Monique , Salle Gildas Le Gal La , Rougier Alain
Published: August 2005

Summary: Purpose: Correlations between granule cell dispersion (GCD), collateral mossy fiber (MF) sprouting, and hippocampal cell loss were studied to assess the relation between GCD and synaptic reorganization in the dentate gyrus of patients with epilepsy.

Methods: Twenty specimens from patients with medically intractable temporal lobe epilepsy (TLE) were studied along with two control specimens. GCD was considered to be present when the stratum granulosum was wider than 120 μm, the close apposition between the granule cell (GC) soma was lost, and GCs were scattered in the molecular layer (ML). Patterns of MF sprouting were differentiated as wide or narrow according to the area of neo‐Timm's staining in the ML. GC loss and volumetric cell‐density decreases in the different subfields were assessed.

Results: MF sprouting was observed in 16 (80%) and GCD in nine (45%) cases. A significant correlation was found between MF sprouting and cell loss in all the subfields except the cornu Ammonis field 2 (CA2). A wide band of MF sprouting was associated with severe cell loss. Cases with GCD had a wide band of MF sprouting and also a higher degree of cell loss than cases without GCD.

Conclusion: GCD is associated with a specific pattern of MF sprouting, but cell loss was found to be a major determinant for MF reorganization.
Periictal Diffusion‐Weighted Imaging in a Case of Lesional Epilepsy
Authors: Diehl B. , Najm I. , Ruggieri P. , Foldvary N. , Mohamed A. , Tkach J. , Morris H. , Barnett G. , Fisher E. , Duda J. , Lüders H. O.
Published: August 2005

Summary: Purpose: Diffusion‐weighted MR imaging (DWI) has been used for the early diagnosis of acute ischemic lesions in humans and in animal models of focal status epilepticus. We hypothesized that DWI may be a sensitive, noninvasive tool for the localization of the epileptogenic area during the periictal period.

Methods: A periictal DWI study was performed on a 35‐year‐old patient during focal status epilepticus with repetitive prolonged focal motor seizures originating from a lesion in the right frontal lobe. DWI results were analyzed visually and by calculating apparent diffusion coefficient (ADC) maps.

Results: On DWI, a single area of signal increase (decrease in ADC) was found in the region of focal electrocorticographic seizures that was mapped intraoperatively.

Conclusions: Ictal/postictal DWI may be a useful technique for seizure localization in patients with lesional epilepsy.
Hippocampal and Entorhinal Cortex High‐Frequency Oscillations (100–500 Hz) in Human Epileptic Brain and in Kainic Acid‐Treated Rats with Chronic Seizures
Authors: Bragin Anatol , Engel Jerome , Wilson Charles L. , Fried Itzhak , Mathern Gary W.
Published: August 2005

Summary: Purpose: Properties of oscillations with frequencies >100 Hz were studied in kainic acid (KA)‐treated rats and compared with those recorded in normal and kindled rats as well as in patients with epilepsy to determine differences associated with epilepsy.

Methods: Prolonged in vivo wideband recordings of electrical activity were made in hippocampus and entorhinal cortex (EC) of (a) normal rats, (b) kindled rats, (c) rats having chronic recurrent spontaneous seizures after intrahippocampal KA injections, and (d) patients with epilepsy undergoing depth electrode evaluation in preparation for surgical treatment.

Results: Intermittent oscillatory activity ranging from 100 to 200 Hz in frequency and 50–150 ms in duration was recorded in CA1 and EC of all three animal groups, and in epileptic human hippocampus and EC. This activity had the same characteristics in all groups, resembled previously observed “ripples” described by Buzsáki et al., and appeared to represent field potentials of inhibitory postsynaptic potentials (IPSPs) on principal cells. Unexpectedly, higher frequency intermittent oscillatory activity ranging from 200 to 500 Hz and 10–100 ms in duration was encountered only in KA‐treated rats and patients with epilepsy. These oscillations, termed fast ripples (FRs), were found only adjacent to the epileptogenic lesion in hippocampus, EC, and dentate gyrus, and appeared to represent field potential population spikes. Their local origin was indicated by correspondence with the negative phase of burst discharges of putative pyramidal cells.

Conclusions: The persistence of normal‐appearing ripples in epileptic brain support the view that inhibitory processes are preserved. FRs appear to be field potentials reflecting hypersynchronous bursting of excitatory neurons and provide an opportunity to study the role of this pathophysiologic phenomenon in epilepsy and seizure initiation. Furthermore, if FR activity is unique to brain areas capable of generating spontaneous seizures, its identification could be a powerful functional indicator of the epileptic region in patients evaluated for surgical treatment.
Influence of Valproate Monotherapy on Platelet Activation and Hematologic Values
Authors: Zeller Joern A. , Schlesinger Stefan , Runge Uwe , Kessler C.
Published: August 2005

Summary: Purpose: Valproate (VPA) has been linked to coagulation disturbances, with both impaired and exaggerated clotting, which has been attributed to an effect of VPA on platelets or hemostatic proteins. Additional thrombocytic function testing may help to identify patients at risk of increased bleeding caused by platelet dysfunction.

Methods: We evaluated the influence of VPA on hematologic routine values and platelet activation by using immunostaining and flow cytometry in 30 patients receiving long‐term VPA therapy and in 30 controls.

Results: The fraction of activated platelets was similar in both groups; however, the general extent of platelet activation was significantly lower in the patient group, with considerable interindividual variability. In addition, patients had a significantly lower platelet count, prolonged thrombin time, and higher mean corpuscular hemoglobin.

Conclusions: Our data confirm the previously reported hematologic changes caused by VPA and additionally suggest that VPA impairs procoagulatory thrombocytic function, which is reflected by reduced platelet activation and increased thrombin time. Possible mechanisms of VPA‐platelet interaction are discussed.
Components of Attention in Children with Complex Partial Seizures With and Without ADHD
Authors: Semrud‐Clikeman Margaret , Wical Beverly
Published: August 2005

Summary: Purpose: To evaluate attentional difficulties in children with complex partial seizures, we reviewed the records of 12 children with complex partial seizures with attention deficient hyperactivity disorder (CPS/ADHD); 21 children with CPS without ADHD (CPS); 22 children with ADHD; and 15 control children.

Methods: Each child completed a computerized performance test (CPT), which evaluated sustained attention, inhibition of response, response time, and consistency of response. The ADHD groups also completed the CPT after a dose of methylphenidate.

Results: The results found poorest performance on the CPT by the CPS/ADHD group. Particular difficulty in attention was found for children with epilepsy regardless of the ADHD diagnosis. When methylphenidate was administered to the ADHD groups, both groups improved in performance on the CPT.

Conclusions: Epilepsy may predispose children to attention problems that can significantly interfere with learning. Similar improvement for children with CPS/ADHD was found with methylphenidate compared with baseline as for children with ADHD but without CPS.
Teratogenic Effects of Antiepileptic Drugs: Use of an International Database on Malformations and Drug Exposure (MADRE)
Authors: Arpino Carla , Brescianini Sonia , Robert Elisabeth , Castilla Eduardo E. , Cocchi Guido , Cornel Martina C. , de Vigan Catherine , Lancaster Paul A. L. , Merlob Paul , Sumiyoshi Yoshio , Zampino Giuseppe , Renzi Cristina , Rosano Aldo , Mastroiacovo Pierpaolo
Published: August 2005

Summary: Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations.

Methods: Information on all malformed infants (1990–1996) with maternal first‐trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries.

Results: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid.

Conclusions: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports.
Effects of Vigabatrin on Sleep–Wakefulness Cycle in Amygdala‐Kindled Rats
Authors: Raol Y. H. , Meti B. L.
Published: August 2005

Summary: Purpose: Our aim was to study the effect of prolonged administration of vigabatrin (VGB) on sleep‐wakefulness cycle in kindled seizure‐induced rats.

Methods: Adult male Wistar rats were implanted stereotaxically with electrodes for kindling and polysomnography. The rats were divided into two groups, kindled and VGB‐treated kindled rats. VGB was administered intraperitonially every day for 21 days, and polysomnographic recordings were taken after doses 1, 7, 14, and 21. The drug effects were evaluated by comparing the records of kindled and drug‐treated kindled rats.

Results: The VGB‐administered kindled rats showed an increase in total sleep time (TST) due to an increase in total non‐rapid eye movement (NREM) and light slow‐wave sleep stage I (SI) with a decrease in wakefulness. The number of episodes and REM onset latencies were found to be decreased after drug treatment.

Conclusions: It can therefore be concluded that VGB has a somnolence‐inducing effect and that it might mediate its anti‐convulsant effect by altering sleep architecture through sleep‐regulating areas.
The Cost of Epilepsy in the United States: An Estimate from Population‐Based Clinical and Survey Data
Authors: Begley Charles E. , Famulari Melissa , Annegers John F. , Lairson David R. , Reynolds Thomas F. , Coan Sharon , Dubinsky Stephanie , Newmark Michael E. , Leibson Cynthia , So E. L. , Rocca Walter A.
Published: August 2005

Summary: Purpose: To provide 1995 estimates of the lifetime and annual cost of epilepsy in the United States using data from patients with epilepsy, and adjusting for the effects of comorbidities and socioeconomic conditions.

Methods: Direct treatment‐related costs of epilepsy from onset through 6 years were derived from billing and medical chart data for 608 population‐based incident cases at two sites in different regions of the country. Indirect productivity‐related costs were derived from a survey of 1,168 adult patients visiting regional treatment centers. Direct costs separate the effects of epilepsy and comorbidity conditions. Indirect costs account for the effects of other disabilities and socioeconomic conditions on foregone earnings and household activity. The estimates were applied to 1995 population figures to derive national projections of the lifetime and annual costs of the disorder.

Results: The lifetime cost of epilepsy for an estimated 181,000 people with onset in 1995 is projected at $11.1 billion, and the annual cost for the estimated 2.3 million prevalent cases is estimated at $12.5 billion. Indirect costs account for 85% of the total and, with direct costs, are concentrated in people with intractable epilepsy.

Conclusions: Direct costs attributable to epilepsy are below previous estimates. Indirect costs adjusted for the socioeconomic conditions of patients are above previous estimates. Findings indicate that epilepsy is unique in the large proportion of costs that are productivity‐related, justifying further investment in the development of effective interventions.