bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose–Response Study of Vigabatrin as Add‐On Therapy in Patients with Uncontrolled Complex Partial Seizures
Authors: Dean Christine , Mosier Michael , Penry Kiffin
Published: August 2005

Summary: Purpose: This placebo‐controlled, randomized, double‐blind, multicenter study examined the efficacy and safety of three daily doses of vigabatrin (VGB; 1, 3, or 6 g) as add‐on therapy in 174 patients with previously uncontrolled complex partial seizures with or without secondary generalization.

Methods: A 12‐week pretreatment assessment period was followed by drug therapy with a 6‐week titration period and a 12‐week maintenance phase.

Results: VGB doses of 3 and 6 g/day reduced median monthly frequency of seizures by 4.3 and 4.5 seizures, respectively, compared with 0.2 seizures for placebo (p = 0.0001). The percentages of patients classified as therapeutic successes (≤50% reduction in seizure frequency) were 7% for placebo and 24, 51, and 54% for patients taking daily VGB doses of 1, 3, and 6 g, respectively; the comparison with placebo was significant for all treatment groups. The linear trend for dose response was highly significant (p ≥ 0.0001) for both median monthly seizure frequency and therapeutic success. Vigabatrin was well tolerated, causing no clinically significant changes in laboratory parameters, brain magnetic resonance imaging, evoked potentials, cognitive function, or psychosocial tests. Fatigue, drowsiness, and dizziness were the most common treatment‐related adverse events in all treatment groups. Dropouts due to adverse events were higher in the 6‐g/day group.

Conclusions: VGB was significantly more effective than placebo as add‐on therapy in reducing seizure frequency. VGB at 3 and 6 g/day produced the best efficacy: however, adverse events may limit the use of the 6‐g/day dose in some patients.
Limbic Seizures Alter Reproductive Function in the Female Rat
Authors: Edwards Heather E. , Burnham W. McIntyre , Ng M. Mark , Asa Sylvia , MacLusky Neil J.
Published: August 2005

Summary: Purpose: Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction.

Methods: Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham‐kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears.

Results: Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham‐kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P4 administration restored cyclicity in all five shamkindled controls that had spontaneously stopped cycling. P4 treatment to kindled females in PVC resulted in a different endocrine profile than that in non‐P4‐treated, kindled rats in PVC. P4‐treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers.

Conclusions: Seizures initiated in the amygdala result in impairment of the hypothalamic‐pituitary axis, resulting in loss of ovarian cyclicity.
Effects of Vigabatrin on the GABAergic System as Determined by [123I]Iomazenil SPECT and GABA MRS
Authors: Verhoeff Nicolaas Paul L. G. , Petroff Ognen A. C. , Hyder Fahmeed , Zoghbi Sami S. , Fujita Masahiro , Rajeevan Nallakkandi , Rothman Douglas L. , Seibyl John P. , Mattson Richard H. , Innis Robert B.
Published: August 2005

Summary: Purpose: To evaluate effects of vigabatrin (VGB) by using [123I]iomazenil single‐photon emission computed tomography (SPECT) to estimate central γ‐aminobutyric acid (GABAA)/benzodiazepine receptors (BZRs), and magnetic resonance spectroscopy (MRS) to assess tissue GABA levels.

Methods: Six patients with partial seizures had both SPECT and MRS before and 25–84 days after starting VGB (3 g p.o., q.d.). SPECT was acquired by using the constant‐infusion method and, after nonuniform attenuation correction, coregistered with T1‐weighted MR Imaging (MRI) A volume of interest (VOI) of 3 × 2 × 2 cc over the occipital cortex, used for MRS acquisition, was positioned on both MRI and coregistered SPECT. Occipital activity was divided by either total plasma activity or plasma [123I]iomazenil concentration to estimate BZR distribution volume (VT‐p and V'T, respectively). Wilcoxon's test was used for VOI differences in GABA levels, BZR VT‐p or V'T. SPM96 (either no global normalization or proportional scaling) was used to compare BZR VT‐p changes in the patients with and without VGB with test‐retest data in eight healthy age‐matched controls.

Results: Occipital GABA levels were increased threefold (without VGB, 1.1 ± 0.1μmol/g; with VGB, 2.9 ± 0.5 μmol/g; p = 0.027). BZR distribution volumes showed no change, when estimated by either VT‐p (without VGB, 6.00 ± 0.91 ml/g; with VGB, 5.86 ± 0.44 ml/g; p = 0.92) or V'T (without VGB, 41.1 ± 11.2 ml/g; with VGB, 41.2 ± 9.9 ml/g; p = 0.75). No significant changes were detected by SPM96.

Conclusions: A clinically effective dose of VGB caused a threefold increase in tissue GABA levels but was not associated with a substantial BZR downregulation.
Bradycardia and Asystole with the Use of Vagus Nerve Stimulation for the Treatment of Epilepsy: A Rare Complication of Intraoperative Device Testing
Authors: Asconapé Jorge J. , Moore David D. , Zipes Douglas P. , Hartman Laura M. , Duffell William H.
Published: August 2005

Summary: Purposes: A 56‐year‐old man with mild mental retardation, right congenital hemiparesis, and refractory partial seizures was referred for vagus nerve stimulation (VNS).

Methods: Routine lead diagnostic testing during the surgical procedure (1.0 mA, 20 Hz, and 500 μs, for ˜ 17 s) resulted, during the initial two stimulations, in a bradycardia of ˜30 beats/min. A third attempt led to transient asystole that required atropine and brief cardiopulmonary resuscitation.

Results: The procedure was immediately terminated, the device removed, and the patient recovered completely. A postoperative cardiologic evaluation, including an ECG, 24‐h Holter monitor, echocardiogram, and a tilt‐table test, was normal.

Conclusions: Possible mechanisms for the bradycardia/asystole include stimulation of cervical cardiac branches of the vagus nerve either by collateral current spread or directly by inadvertent placement of the electrodes on one of these branches; improper plugging of the electrodes into the pulse generator, resulting in erratic varying intensity of stimulation; reverse polarity; and idiosyncratic‐type reaction in a hypersusceptible individual. The manufacturer reports the occurrence rate in ˜3,500 implants for this intraoperative event to be approximately one in 875 cases or 0.1%.
Ictal Video‐EEG Recording of Three Partial Seizures in a Patient with the Benign Infantile Convulsions Associated with Mild Gastroenteritis
Authors: Imai Katsumi , Otani Kazumasa , Yanagihara Keiko , Li Zhong‐gi , Futagi Yasuyuki , Ono Jiro , Nagai Toshisaburo , Okada Shintaro
Published: August 2005

Summary: Purpose: In infants, benign convulsions can be triggered by febrile illness or mild diarrhea such as Rotavirus gastroenteritis. The triggering mechanism of these convulsions is still unknown. In spite of several reports concerning clinical features, the ictal EEG recordings were rarely analyzed by a video‐EEG monitoring system. To reveal a clue for the triggering mechanism of these convulsions, we analyzed the correlation of clinical manifestations and the EEG discharges during the ictal events and compared with previous reports.

Methods: The ictal EEG of a cluster of three afebrile convulsions associated with mild gastroenteritis was recorded by an EEG closed‐circuit TV (EEG‐CCTV) monitoring system in a 6‐month‐old healthy female infant.

Results: All seizures began as complex partial seizures (CPSs), which exhibited a motionless stare with or without leftward deviation of both eyes, and evolved to secondarily generalized tonic‐clonic seizures (SGTCSs) for −90 s. Each of three ictal discharges began from the right occipital, right centroparietotemporal, and left occipital regions, respectively.

Conclusions: Although initiating sites of ictal discharges of benign infantile convulsions associated with mild gastroenteritis (BICE) were previously reported to be variable among patients, these results indicated that those differ among seizures even in a same infant.
Prevalence of Epilepsy in Rural Iceland: A Population‐Based Study
Authors: Olafsson Elias , Hauser W. Allen
Published: August 2005

Summary: Purpose: To determine the prevalence of epilepsy (recurrent unprovoked seizures) in the population of rural Iceland.

Methods: Review of records of primary‐care facilities for the population of rural Iceland supplemented by review of referrals to electroencephalographic facilities and neurologic specialists to identify all individuals with unprovoked seizures or receiving treatment for epilepsy in the calendar year 1993.

Results: Crude prevalence was 4.8 per 1,000 and was 4.8/1,000 after age adjustment to the 1970 United States population. Age‐adjusted prevalence was higher in male (5.1) than in female subjects (4.4) and increased with advancing age. Sixty‐two percent of prevalence cases were of unknown cause. Sixty‐three percent of cases had major motor seizures without aura or generalized epileptiform pattern on EEG. Sixty‐four percent of patients had had seizures in the year of observation. Seizure control was inversely correlated with number of medications. Ten percent of the prevalence group was taking no medication, although the frequency of seizures was high in this medication‐free group.

Conclusions: Prevalence of epilepsy in rural Iceland is consistent with that reported in recent studies in other developed countries. The data provide insights into the approaches of treatment and use of specialized diagnostic testing in the country. The prevalence is similar to that in other European countries but lower than that reported from rural areas in Latin America.
The Assessment and Treatment of Concerns and Anxiety in Patients Undergoing Presurgical Monitoring for Epilepsy
Authors: Andrewes David , Camp Krystyne , Kilpatrick Christine , Cook Mark
Published: August 2005

Summary:Purpose:This study investigated the impact of a treatment information package on patients being monitored for possible surgical treatment for temporal lobe epilepsy.

Methods:One hundred patients were randomly assigned to either a high‐ or low‐information preparation condition. Levels of anxiety were tested soon after admission by using the Hospital Anxiety and Depression Scale (HADS), The State‐Trait Anxiety Inventory (STAI), and a newly devised questionnaire to assess specific concerns and anxieties of epilepsy patients presenting for monitoring and surgery, the Concerns About Epilepsy Monitoring Questionnaire (CAEMQ). Dispositional desire for information was assessed by the Miller Behavioural Style Scale (MBSS) to investigate whether coping disposition affected coping styles in the hospital setting. Patients assigned to the high‐information condition were exposed to an intervention package, which included viewing a video depicting two separate interviews with patients who had undergone surgery as well as an information package, which described the various tests that the patient would undergo in the course of the monitoring procedure. Patients assigned to the low‐information group were given information that the hospital provided to all patients in their care. All subjects were then retested on anxiety levels a few days later.

Results:Those in the high‐information group showed a significant decrease in anxiety and depression levels compared with those in the low‐information group.

Conclusions:Within the main findings, an effect of dispositional style was found. Identification as either a monitor or blunter on the MBSS showed different coping strategies on arrival in hospital as measured by the CAEMQ, indicating that the level of information given to patients with epilepsy on arrival needs to be mediated by awareness of these two dispositional styles so that they obtain maximal benefit from the information to which patients with epilepsy are exposed.
Pre‐ and Postoperative Neuropsychological Profiles in Children and Adolescents with Temporal Lobe Epilepsy
Authors: Lendt Michael , Helmstaedter Christoph , Elger Christian Erich
Published: August 2005

Summary: Purpose: To evaluate the neuropsychological performance of children before and after temporal lobe resection (TLR).

Methods: Memory, attention, language, and visuoconstructive abilities were examined in 20 children (age 10–16 years) before, and 3 and 12 months after TLR (right, n = 10; left, n = 10; two‐thirds anterior resection, n = 16; amygdalohippocampectomy, n = 4). Preoperative performance was compared with data of 30 age‐matched healthy children; changes in performance after surgery were determined by repeated‐measurement multivariate analysis of variance (MANOVA) and by use of reliable change indices (RCI).

Results: Preoperatively, no differences were observed between patients and controls in verbal and figural memory performance. Children with temporal lobe epilepsy (TLE), however, and particularly those with a left temporal focus, showed significantly reduced language performance. Repeated‐measurement statistics indicated that memory performance did not change after surgery, whereas language performance and attention significantly improved 3 months and 1 year after surgery, respectively. Individual evaluations of memory showed gains in five children and deterioration in four children. Poor seizure control appeared the decisive variable characterizing children with losses in memory.

Conclusions: Compared with adults, pre‐ and postoperative memory data suggest less pronounced hemispheric differences in school‐age children with TLE. The results raise the possibility that children have a lower risk of memory deterioration after TLR, which may be due to their larger potential for cerebral plasticity.
EEG Background Delta Activity in Temporal Lobe Epilepsy: Correlation with Volumetric and Spectroscopic Imaging
Authors: Bernasconi Andrea , Cendes Fernando , Lee Jong , Reutens D. C. , Gotman Jean
Published: August 2005

Summary: Purpose: With quantitative electroencephalogram (EEG) and neuroimaging methods, we examined delta activity, atrophy, and neuronal‐axonal dysfunction of the cerebral gray and white matter in patients with intractable temporal lobe epilepsy (TLE). Based on evidence that lesions of the white matter result in EEG delta activity, we postulated that background abnormalities in patients with TLE are related to changes of the temporal lobe white matter.

Methods: We measured interictal delta activity in 34 TLE patients and 10 controls. Spike‐free and artifact‐free EEG samples were selected by visual inspection. A spectral analysis was used to compute the energy in the delta frequency band. We compared the results of the spectral analysis to magnetic resonance imaging‐ (MRI) based volumes of the temporal lobe white and gray matter, the hippocampus and the amygdala and N‐acetyl aspartate (NAA) in the lateral and posterior temporal lobe by using proton magnetic resonance spectroscopic imaging (1H‐MRSI). The degree of correlation between delta activity and the neuroimaging measurements was assessed by using the Pearson correlation coefficient (r). An analysis of variance (ANOVA) was used to examine the influence of the seizure‐focus lateralization on the delta activity and the neuroimaging parameters.

Results: There was no significant difference in the amount of delta activity in the temporal lobe between the controls and patients. We found no correlation between delta activity and the neuroimaging measures (p < 0.05). The ANOVA showed significant differences between the patients and controls for the volume of the gray and white matter of the temporal lobe and for the NAA in the lateral and posterior temporal lobe (p > 0.002).

Conclusions: The interictal background delta activity was not explained by reduced volume of the temporal lobe white matter, gray matter, or by abnormalities seen in 1H‐MRSI.
Continuous Spike‐and‐Wave Activity During Slow‐Wave Sleep: Syndrome or EEG Pattern?
Authors: Veggiotti Pierangelo , Beccaria Francesca , Guerrini Renzo , Capovilla Giuseppe , Lanzi Giovanni
Published: August 2005

Summary: Purpose: We reviewed the electroclinical pictures and clinical characteristics of 32 patients with continuous spike‐and‐wave activity during slow sleep (CSWS) to ascertain to what extent this electroencephalogram (EEG) pattern is associated with the age‐related CSWS syndrome as defined by the International League Against Epilepsy (ILAE) International Classification or with different clinical settings.

Methods: We reviewed clinical and EEG characteristics of 32 CSWS patients.

Results: In all patients, detection of CSWS coincided with a worsening of neurologic status. Ten (34%) patients had the typical features of CSWS syndrome, four were classified as having Landau‐Kleffner syndrome, and three had acquired opercular syndromes. The remaining 15 patients, all with symptomatic epilepsy, had CSWS, which lasted for variable periods and might be related to inappropriate drug choice. Three patients of this group had unilateral CSWS and exhibited worsening of spontaneous movements in the hemibody contra‐lateral to CSWS activity lasting for a few hours after awakening.

Conclusions: Our data show that a number of factors can intervene in the genesis of CSWS, which may explain the variability of the associated clinical conditions. In view of this etiologic heterogeneity, it is not possible to classify all the patients with CSWS as having the CSWS syndrome. Therefore, the CSWS syndrome should be considered a category embracing a limited group of patients, whereas the EEG pattern of CSWS is seen commonly in various clinical conditions.
Randomised, Placebo‐Controlled Study of Vigabatrin as First‐Line Treatment of Infantile Spasms
Authors: Appleton R. E. , Peters A. C. B. , Mumford J. P. , Shaw D. E.
Published: August 2005

Summary: Purpose: Vigabatrin (VGB) has been shown to be an effective drug in the treatment of infantile spasms (West syndrome) in predominantly retrospective and open but also in prospective studies. This prospective, randomised, and placebo‐controlled trial of VGB in infantile spasms was considered to be justified and feasible to confirm or refute these previous findings.

Methods: Forty children with newly diagnosed infantile spasms received either VGB or placebo for 5 days in a double blind, placebo‐controlled, parallel‐group study, after which all the infants continuing in the study were treated openly with VGB for a minimum of 24 weeks.

Results: Compared with baseline, at the end of the double‐blind phase, the patients treated with VGB had a 78% (95% confidence interval, 55–89%) reduction in spasms compared with 26% (–56–65%) in the group treated with placebo (p = 0.020). Seven VGB‐treated patients and two placebo‐treated patients were spasm free on the final day of the double‐blind period (p = 0.063). At the end of the study, 15 children (38% of the original 40 patients or 42% of the 36 patients who entered the open phase) were spasm free with VGB monotherapy. No patient withdrew from the study because of an adverse event.

Conclusions: This unique randomized, placebo‐controlled study is the first to demonstrate the efficacy of a specific drug in the treatment of West syndrome and supports the results of previously published open and prospective trials. It further confirms that VGB could be considered as the drug of first choice in treating infantile spasms.
White‐Matter Change in Mesial Temporal Sclerosis: Correlation of MRI with PET, Pathology, and Clinical Features
Authors: Choi Dongil , Na Dong Gyu , Byun Hong Sik , Suh Yeon‐Lim , Kim Sang Eun , Ro Duk Woo , Chung II Gyu , Hong Seung‐Chyul , Hong Seung Bong
Published: August 2005

Summary: Purpose: To assess the magnetic resonance imaging (MRI), positron emission tomography (PET), pathology, and clinical findings of patients with the MRI feature of white‐matter change (WMC) in the anterior temporal lobe.

Methods: Fifty‐six patients with pathologically proven mesial temporal sclerosis were included in this study. MRI and 18F‐2‐deoxyglucose‐(FDG) PET images were obtained before surgery in all patients. The patients were divided into two groups according to the presence of WMC on their MRI. WMC consists of an indistinct gray‐white matter demarcation and an increased signal intensity of the anterior temporal lobe on T2‐weighted images. The two groups were then compared in terms of MRI, PET, pathology, and clinical features.

Results: The MRI feature of WMC was observed in 18 (32%) of the 56 patients. PET images of those patients revealed more severe hypometabolism of the ipsilateral temporal lobes (p > 0.05). In terms of histologic findings, larger numbers of het‐erotopic neurons were observed in the anterior temporal lobe white matter of these patients who also shared the following clinical features: earlier seizure onset, frequent history of febrile convulsions, and favorable surgical outcomes.

Conclusions: The MRI feature of WMC is an additive sign for correct seizure lateralization and may be related to a favorable surgical outcome in patients with temporal lobe epilepsy.
The EEG and Prognosis in Status Epilepticus
Authors: Nei Maromi , Lee Jin‐Moo , Shanker Vicki L. , Sperling Michael R.
Published: August 2005

Summary: Purpose: To examine the relation between specific EEG features and clinical outcome, determine whether a predictable sequence of EEG patterns exists during status epilepticus (SE), and examine the relation between periodic epileptiform discharges (PEDs) and SE.

Methods: EEG records of 50 patients with SE admitted to Graduate Hospital between January 1990 and July 1995 were reviewed. Ictal EEGs were available in 72%; 28% had only postictal EEGs. Poor outcome was defined as death or persistent vegetative state, and good outcome as all others. Fisher's Exact test, x2, and t tests were performed for data analysis.

Results: Of 50 patients, 72% had a good outcome and 28%, a poor outcome. If PEDs were present at any time during or after SE, outcome tended to be worse (p = 0.053). With PEDs, eight (44%) of 18 had a poor outcome; without PEDs, six (19%) of 32 had a poor outcome. Etiologies for SE did not substantially differ in patients with or without PEDs, and structural abnormalities were not more associated with the presence of PEDs. PEDs were seen both early and late, during and after SE. Other EEG characteristics (lateralized vs. bilateral symmetric ictal EEG, discrete vs. continuous ictal activity, and postictal focal slowing) did not relate to outcome. No predictable sequence of EEG changes was found during SE.

Conclusions: PEDs are the only EEG feature related to outcome in SE and are associated with poor outcome independent of etiology.
Self‐Efficacy and Social Support as Mediators in the Relation Between Disease Severity and Quality of Life in Patients with Epilepsy
Authors: Amir Marianne , Roziner Ilan , Knoll Alon , Neufeld Miriam Y.
Published: August 2005

Summary: Purpose: This study examined the influence of two psychosocial variables mediating between disease severity and quality of life (Qol) in epilepsy; social support and mastery (measured by locus of control and self‐efficacy). A model placing these two variables as mediators between disease severity and QoL was tested with structural equation modeling.

Methods: Eighty‐nine patients with epilepsy (58% men, age 36 ± 12 years) were given the following instruments: Liverpool Seizure Severity Scale, Interpersonal Support Evaluation List, Epileptic Self‐Efficacy Scale, Locus of Control scale, and the World Health Organization's Quality of Life Questionnaire, the WHOQOL.

Results: Structural equation modeling showed good fit between the research model and the data (Bentler‐Bonett Normalized Index of fit, 0.96; LISREL GFI, 0.95). Ninety percent of the variance of the WHOQOL was explained by a combination of disease severity, self‐efficacy in epilepsy, social support, and locus of control. Mastery was found to mediate the correlation between disease severity and QoL, and social support was found to act as a mediator between disease severity and mastery.

Conclusions: The study findings emphasize the possibility of improving QoL among patients with epilepsy by counseling and treatment aimed at reinforcing their self‐efficacy and locus of control, as well as by improving their SoS.
Rasmussen's Encephalitis with Concomitant Cortical Dysplasia: The Role of GluR3
Authors: Palmer Cheryl Ann , Geyer James D. , Keating Janice M. , Gilliam Frank , Kuzniecky Ruben I. , Morawetz Richard B. , Bebin E. Martina
Published: August 2005

Summary: The role of the glutamate receptor GluR3 in Rasmussen's encephalitis is actively under investigation. Autoimmune processes with this receptor as the target are currently theorized. We provide an additional case of pathologically proved Rasmussen's encephalitis (with concomitant cortical dysplasia) in the presence of antibodies against the GluR3 receptor.
Dietary Fat, Ketosis, and Seizure Resistance in Rats on the Ketogenic Diet
Authors: Likhodii Sergei S. , Musa Kathy , Mendonca Antonio , Dell Cynthia , Burnham W. McIntyre , Cunnane Stephen C.
Published: August 2005

Summary: Purpose: Fat is the major component of the ketogenic diet (KD), yet no studies have examined whether the type of fat used in the diet can be optimized to provide additional benefits. The purpose of the present experiments was to compare the efficiency of different fats in inducing ketosis and affording seizure resistance.

Methods: The effects of KDs that incorporate lard, butter, medium‐chain triglycerides (MCT), or flaxseed oil or a mixture of the latter three fats were examined in rats fed KD for up to 98 days. The maximal electroshock (MES) or pentylenetetrazole (PTZ) threshold tests were used to assess seizure susceptibility in two separate experiments.

Results: The rank order of induced ketosis was MCT < mixture < flaxseed oil ± lard = butter < control. MES failed to reveal anticonvulsant effects, but the PTZ test indicated that up to 50% of rats fed the KD were seizure protected (p <0.05). The measures of seizure protection, seizure incidence and score, did not correlate, however, with the level of ketosis in the range of 0.7–5.2 mmol/L for β‐hydroxybutyrate. In the long‐term study, flaxseed oil KD maintained stable ketosis throughout 98 days, whereas ketones declined with lard and butter KD to the control level.

Conclusions: Seizure protection with the versions of the KD did not improve with the higher level of ketosis. The focus of the KD improvement, therefore, is not the achievement of higher ketosis per se but rather designing a diet that provides steady ketosis, exploits advantages of certain fats for neurological development or seizure protection via a nonketogenic mechanism, and is nutritionally balanced.
Cerebral and Cerebellar Volume Reduction in Children with Intractable Epilepsy
Authors: Lawson John A. , Vogrin Simon , Bleasel Andrew F. , Cook Mark J. , Bye Ann M. E.
Published: August 2005

Summary: Purpose: Adult epilepsy studies have demonstrated cerebral and cerebellar volume reduction beyond the epileptogenic zone, correlating this with an inferior surgical outcome. We determined whether brain volumes were reduced in childhood epilepsy and the significance of this.

Methods: Cerebral, cerebellar, and hippocampal volumes were measured by quantitative magnetic resonance imaging on 112 children (ages 4–18) with epilepsy syndrome determined by video‐EEG telemetry. Eighty‐seven had partial epilepsy and 25 had generalized epilepsy or indeterminate syndrome. Normative volumes were obtained from 44 child controls from the community.

Results: A significant reduction in cerebral (12.6%) and cerebellar (7.9%) volume was present in the epilepsy group compared with controls. Analysis of subgroups revealed that cerebral volume was significantly decreased in frontal lobe and nonlocalized partial epilepsies. The mean hippocampal ratio of 0.73 for mesial temporal lobe epilepsy was significantly less than for all other syndromes and controls. There was no difference in the rate of hippocampal volume reduction between syndromes. There was a significant correlation between IQ and cerebral and cerebellar volume, but not duration or age of onset of epilepsy.

Conclusions: Cerebral and cerebellar volume reduction is common in intractable epilepsy syndromes of childhood. These cross‐sectional data suggest that brain volume reduction is present at epilepsy onset and is not a result of intractable seizures. Hippocampal asymmetry is more sensitive than volume reduction as a marker for mesial temporal lobe epilepsy, but neither measure is specific.
Parent‐ and Patient‐ Validated Content for Pediatric Epilepsy Quality‐of‐Life Assessment
Authors: Arunkumar G. , Wyllie E. , Kotagal P. , Ong H. T. , Gilliam F.
Published: August 2005

Summary: Purpose: The purpose of this study was to assess the parent‐ and patient‐validated content of quality‐of‐life measurement for use in children with epilepsy.

Methods: We asked the parents of 80 consecutive children and adolescents with epilepsy to list in order of importance their concerns about living with or caring for their children with epilepsy. Patients were 3 months to 18 years of age (mean, 10 years) and identified at the outpatient clinic or during hospital stay. To minimize investigator bias, parents and children listed their concerns in a private setting without staff involvement.

Results: Twenty‐six distinct domains were generated by the parents and children. Concerns listed by more than 20 of parents included medication adverse effects (58), cognitive effects of epilepsy (46), prospects for the future (41), safety (35), independence (31), and brain damage caused by seizures (30). Concerns ranked by parents as most important included safety (18), brain damage from seizures (12), enigma of epilepsy (12), cognitive effects of epilepsy (11), and prospects for the future (10). Concerns listed by more than 20 of children included social problems (35), cognitive effects of epilepsy (29), driving (29), sports (27), medication adverse effects (25), and schooling (21). Concerns ranked by children as most important included issues related to medication adverse effects (13), cognitive effects of epilepsy (10), hatred of epilepsy (8), social embarrassment (6), fear of seizures (6), injury (6), and dislike of hospital visits (6).

Conclusion: The effect of epilepsy on health‐related quality of life in pediatric patients is defined by a limited number of domains. A 20‐item inventory was chosen from the 26 domains generated by the parents and children. Our study provides insight into parents' and children's perception of seizures and the impact of epilepsy on everyday life.
Evidence Favoring Genetic Heterogeneity for Febrile Convulsions
Authors: Racacho Lemuel J. , McLachlan Richard S. , Ebers George C. , Maher John , Bulman Dennis E.
Published: August 2005

Summary: Purpose: Two large Canadian kindreds appearing to segregate febrile convulsions as an autosomal dominant trait were evaluated for linkage to three known FC loci, as well as other epilepsy loci.

Methods: Members of the two families were genotyped with microsatellite markers linked to the previously identified febrile convulsion loci, FEB1, FEB2, and GEFS+, and we performed two‐point linkage analyses by assuming an autosomal dominant mode of inheritance.

Results: We report the exclusion of the FC trait in our families to FEB1 on 8q13–21 and to a second febrile convulsion locus on 19p13. Furthermore, we also excluded the GEFS+ locus on 19q13.1 as the cause of febrile convulsions in both kindreds. Microsatellite markers linked to juvenile myoclonic epilepsy (EJM1), benign neonatal familial convulsions EBN1 and EBN2, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), idiopathic generalized epilepsy (EGI), progressive myoclonic epilepsy of Unverricht‐Lundborg (EPM1), and partial epilepsy with auditory features (EPT), were also excluded as potential loci linked to the FC trait in our families.

Conclusions: These findings favor considerable genetic heterogeneity for febrile convulsions.
Induction of Partial Epileptic Seizures by Flumazenil
Authors: Schulze‐Bonhage A. , Elger C. E.
Published: August 2005

Summary: Purpose: This study addressed the efficacy of flumazenil (FMZ) to induce or activate interictal or ictal epileptic discharges in patients with medically intractable partial epilepsies.

Methods: Flumazenil, 1 mg, was injected intravenously in 67 patients undergoing presurgical monitoring for epilepsy surgery, 49 of whom had been treated with benzodiazepines (BZDs) before flumazenil was given. Continuous video electroencephalogram (EEG) monitoring with surface or intracranial electrodes was used to evaluate interictal EEG activity, ictal discharges, and the occurrence and semiology of clinically manifest epileptic seizures.

Results: Interictal epileptiform potentials did not change in frequency or distribution after FMZ. In patients not pretreated with BZDs, epileptic seizures could not be provoked. In eight of the 49 patients pretreated with BZDs, epileptic seizures occurred within 30 min of FMZ application. Seizure semiology and regional EEG onset were identical to seizures recorded without FMZ. Patients operated on according to seizure‐onset localization with FMZ had a >75% reduction in seizure frequency or became seizure free.

Conclusions: Seizure induction by FMZ seems to be a valid method for evaluating seizure semiology and localization of the seizure‐onset zone during presurgical monitoring of patients with medically intractable localization‐related epilepsies.
Planned Ictal FDG PET Imaging for Localization of Extratemporal Epileptic Foci
Authors: Meltzer Carolyn Cidis , Adelson P. David , Brenner Richard P. , Crumrine Patricia K. , Van Cott Anne , Schiff David P. , Townsend David W. , Scheuer Mark L.
Published: August 2005

Summary: Purpose: This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro‐2‐deoxy‐glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratem‐poral origin.

Methods: Ictal PET imaging was performed in four patients (two men and two women, ages 28–61) with continuous or very frequent (every 3–15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single‐photon emission tomography (SPECT) imaging.

Results: Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroen‐cephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case.

Conclusions: We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures.
Contralateral EEG Slowing and Amobarbital Distribution in Wada Test: An Intracarotid SPECT Study
Authors: Hong Seung Bong , Kim Kyung‐won , Seo Dae Won , Kim Sang Eun , Na Dong Gyu , Byun Hong Sik
Published: August 2005

Summary: Purpose: To relate the occurrence of contralateral electroencephalogram slowing (CES) to amobarbital distribution, we performed electroencephalogram (EEG) monitoring and intracarotid single photon emission computed tomography (SPECT) during an intracarotid amobarbital procedure (IAP).

Methods: IAP was performed on 22 patients with temporal lobe epilepsy. CES was defined as the occurrence of significant EEG slowing on the contralateral hemisphere (>50% of the ipsilateral hemisphere slowing) after amobarbital injection. To map the distribution of the amobarbital, we injected a mixture of amobarbital and 99m technetium‐ethylcysteinate dimer (99m Tc‐ECD) into the internal carotid artery and performed a brain SPECT 2 h later. In the SPECT images, regions of interest were determined by ipsilateral and contralateral anterior cerebral artery territories (iACA, cACA), ipsilateral and contralateral middle cerebral artery territories (iMCA, cMCA), and ipsilateral and contralateral posterior cerebral artery territories (iPCA, cPCA), as well as ipsilateral and contralateral anterior and posterior mesial temporal regions (iAMT, cAMT, iPMT, cPMT). The perfusion of amobarbital was interpreted visually in each region.

Results: Amobarbital was distributed in the iMCA in all the patients; in the iACA in 20 (90.9%) patients; in the iAMT in 14 (63.5%); and in the iPCA and iPMT in only two (9.1%). CES was observed in 13 (59.1%) patients. Cross‐perfusion of amobarbital in limited areas of the cACA were observed in only four of 13 patients. Wada retention memory scores (WRMS) showed no significant difference between the CES‐ (n = 9) and CES+ (n = 13) groups.

Conclusions: Amobarbital rarely perfused the iPCA territory and the iPMT region and was rarely delivered to the contralat‐eral hemisphere. The occurrence of CES was not related to the cross‐perfusion of amobarbital. CES appears to be produced by a transient functional disconnection from the ipsilateral hemisphere.
Ictal Spiking Patterns Recorded from Temporal Depth Electrodes Predict Good Outcome After Anterior Temporal Lobectomy
Authors: Schuh Lori A. , Henry Thomas R. , Ross Donald A. , Smith Brien J. , Elisevich Kost , Drury Ivo
Published: August 2005

Summary: Purpose: Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL).

Methods: All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow‐up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were X2, Fisher exact test, and Wilcoxon rank sum.

Results: Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow‐up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 ± 0.3) compared with other outcomes (mean, 0.30 ± 0.3, p = 0.02).

Conclusions: The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.
Atypical Evolutions of Benign Localization‐Related Epilepsies in Children: Are They Predictable?
Authors: Fejerman Natalio , Caraballo Roberto , Tenembaum Silvia N.
Published: August 2005

Summary: Purpose: To emphasize that, in some patients, different atypical evolutions occur in the course of so‐called benign focal epilepsies of childhood (BFEC) and to promote interest in finding clinical and/or electroencephalographic (EEG) clues to which patients might be prone to these risky evolutions.

Methods: Twenty‐six patients who started with the typical clinical and EEG features of benign childhood epilepsy with centrotemporal spikes (BCECTS) but who had reversible or persistent, serious epileptic events including status epilepticus and language, cognitive, or behavioral impairments were followed for <14 years. Repeated neurologic examinations, EEG records, and neuropsychological evaluations were done, and brain‐imaging studies [computerized axial tomography (CAT) or magnetic resonance imaging (MRI)] were obtained in all patients.

Results: The 26 patients were in four separate groups according to the nature of their atypical evolution. Eleven children had atypical benign focal epilepsy of childhood (ABFEC), three with Landau–Kleffner syndrome (LKS), seven with status epilepticus of BCECTS, and five with mixed features of the other three groups. All the children whose BCECTS evolved into ABFEC have finally recovered and are attending normal schools, although five have learning difficulties. Two of the three patients diagnosed with LKS recovered from aphasia, although some language difficulties persist in one. The seven who showed status epilepticus of BCECTS are now normal after 3–14 years of follow‐up, and three of the five children showing mixed features fulfilled the criteria for a diagnosis of epilepsy with continuous spikes and waves during slow sleep (CSWS).

Conclusions: A small proportion of cases starting with BCECTS evolve into ABFEC, LKS, status of BCECTS, or epilepsy with CSWS. In such cases, BCECTS is not always benign. Clinical and EEG markers should be sought to predict these atypical evolutions.
Long‐Term Seizure Outcome in 74 Patients with Lennox–Gastaut Syndrome: Effects of Incorporating MRI Head Imaging in Defining the Cryptogenic Subgroup
Authors: Goldsmith Ian L. , Zupanc Mary L. , Buchhalter Jeffrey R.
Published: August 2005

Summary: Purpose: To determine if using more stringent criteria for cryptogenic Lennox‐Gastaut syndrome (LGS) would result in an improved prognosis for that group. Cryptogenic, symptomatic, and non‐cryptogenic LGS patients without etiology (indeterminate) were compared with respect to seizure and cognitive outcome.

Methods: Retrospective chart review was performed on 245 patients seen at the Mayo Clinic Rochester from 1976 to 1997, with a diagnosis of either LGS or slow spike wave on EEG. LGS was confirmed in 107 (64 male, 43 female) patients. This group was divided into cryptogenic, symptomatic, and indeterminate groups containing 23, 47, and 37 patients, respectively. In this study, cryptogenic patients all had normal development before onset of LGS, absence of dysmorphic features, normal neurologic examination, and normal magnetic resonance (MRI) brain imaging. Of the 107 patients, 74 had ≥3 years of follow‐up.

Results: LGS onset in the 107 patients occurred at a median age of 4.0 years (range, 0.6–28.9 years). When last seen, 63% of those with symptomatic LGS had more than three seizures a day compared with 50% of cryptogenic and 34% of indeterminate patients. The most common seizure types were tonic (77%), atypical absence (61%), and generalized tonic‐clonic (56%). Only three patients, all part of the indeterminate group, were seizure free at last follow‐up.

Conclusions: Using stringent criteria in defining the cryptogenic subgroup resulted in no significant difference in seizure outcome. Individuals with a normal cognitive outcome did not segregate into one etiologic subgroup, but did have LGS onset at an older age.
A Comparative Study of Trauma and Posttraumatic Stress Disorder Prevalence in Epilepsy Patients and Psychogenic Nonepileptic Seizure Patients
Authors: Rosenberg Harriet J. , Rosenberg Stanley D. , Williamson Peter D. , Wolford George L.
Published: August 2005

Summary: Purpose: This study tests the hypothesis that trauma histories, including histories of physical and sexual abuse, and posttraumatic stress disorder (PTSD) are more prevalent in psychogenic non–epileptic seizure (NES) patients than in epilepsy patients.

Methods: Thirty‐five inpatients with intractable seizures were evaluated for trauma history and PTSD. After these assessments, patients were diagnosed as having either epileptic or nonepileptic seizures through EEG monitoring.

Results: NES diagnosis correlated with PTSD and total number of lifetime traumas, adult traumas, and abuse traumas. Contrary to previous hypotheses, reported childhood sexual abuse (CSA) did not correlate significantly with NES diagnosis. However, CSA predicted PTSD in a discriminant analysis.

Conclusions: We found evidence for the hypothesized relations between trauma, abuse, PTSD, and NES diagnosis. However, elevated levels in both seizure‐disorder groups suggest that routine assessment for abuse, trauma, and PTSD might facilitate medical care and treatment for all intractable seizure patients.
Repeated Acute Testing of Anticonvulsant Drugs in Amygdala Kindled Rats: Increase in Anticonvulsant But Decrease in Adverse Effect Potential
Authors: Löscher Wolfgang , Fiedler Mia
Published: August 2005

Summary: Purpose: Because preparation of kindled rats is laborious, time‐consuming, and expensive, such animals are often used for several experiments in the evaluation of anticonvulsant drugs (AEDs). Furthermore, for comparison with data on new drugs, often “historical” data on standard drugs obtained in previous experiments in other groups of kindled rats are used. Without knowing how factors such as repeated drug testing or seasonal variation in drug responses affect drug potencies in the kindling model, false conclusions and predictions might be drawn from such comparisons. In this study, we examined the anticonvulsant and adverse effects of the three clinically established AEDs carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) once per month in the same two groups of amygdala‐kindled rats over a period of 9 (group 1) or 6 (group 2) consecutive months. To evaluate the possible effect of the season, experiments in group 1 were started in autumn, and experiments in group 2 in spring.

Methods: For quantification of anticonvulsant activity, the focal seizure threshold (threshold for afterdischarges; ADT) was determined after each acute drug treatment and compared with a control ADT determined 2–3 days before.

Results: The repeated acute (single‐dose) drug testing in the same groups of amygdala‐kindled rats led to three pronounced alterations in the animals: (a) a significant decrease in ADT, (b) a marked potentiation of AED effects on ADT, and (c) a striking reduction in ataxia produced by drug treatments. Drug levels in plasma, which were determined in each drug trial, showed only moderate variation over the period of the experiments, so that the observed alterations in drug responses were certainly not due to pharmacokinetic factors. PB and VPA, but not CBZ, showed a more potent anticonvulsant effect when experiments were started in October (group 1) compared with April (group 2), but this difference was rapidly overridden by the marked and progressive potentiation of anticonvulsant activity on repeated drug testing.

Conclusions: These data demonstrate that repeated use of the same kindled rats for acute drug testing significantly alters the sensitivity of the animals to the anticonvulsant and adverse effects of drugs. Because the anticonvulsant potency increases, whereas the adverse effect potential decreases during repeated acute drug testing, this may lead to false‐positive data on a test compound. The mechanisms involved in these observations deserve further studies.