bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Epilepsy in Patients with Multiple Sclerosis: A Population‐Based Study in Iceland
Authors: Olafsson Elias , Benedikz John , Hauser W. Allen
Published: August 2005

Summary: Purpose: Several clinical series reported an association between multiple sclerosis (MS) and epilepsy. We conducted a total population study in Iceland to determine the risk for developing epilepsy in patients with MS compared with that expected in the general population.

Methods: Medical records of the 188 incidence cases of clinically definite MS first diagnosed in Iceland during the 25‐year study period (1965–1989) were reviewed. The cases were followed up through 1994 or until death to identify those developing seizures or epilepsy. The expected number of cases with epilepsy in the MS‐incidence cohort were calculated based on the age‐specific incidence for epilepsy in Iceland and the age‐specific person years of follow‐up in the MS cohort.

Results: During the 2,771 person years of observation after diagnosis of clinically definite MS, three MS patients developed epilepsy. One additional case developed epilepsy after onset of MS symptoms but before diagnosis of MS. The cumulative incidence of epilepsy by 10 years after diagnosis of MS was 1.9%. Given the age‐specific person years of follow‐up after diagnosis of MS, only one case of epilepsy would have been expected; standardized incidence ratio (SIR), 3.0 (95% confidence interval (CI), 0.6–8.8).

Conclusions: MS is a risk factor for developing epilepsy. Patients with MS have a threefold increase in risk for developing epilepsy when compared with that expected in the general population. The reason for this increased risk is unclear and needs further investigation.
Lamotrigine Therapy in Juvenile Neuronal Ceroid Lipofuscinosis
Authors: Åberg L. , Kirveskari E. , Santavuori P.
Published: August 2005

Summary: Purpose: To evaluate the effects of lamotrigine (LTG) therapy on epileptic seizures and general well‐being in patients with juvenile neuronal ceroid lipofuscinosis (JNCL).

Methods: LTG was initiated in 28 patients with JNCL. The mean age of the patients at the initiation of LTG was 13.7 years (range, 6.7–28.2 years). LTG was started at a dosage of 0.1–0.5 mg/kg/day and increased every 2 weeks until a maintenance dose of 1.25–15 mg/kg/day was reached. On the basis of the indication for LTG therapy, the patients could be divided into four groups. In the first group, LTG was initiated on an add‐on basis; in the second group, LTG was started as the first antiepileptic drug (AED) because of seizures, and in the third group, despite no preceding seizures, because of epileptiform activity in the whole‐night polysomnography; in the fourth group, LTG replaced valproate (VPA), which was discontinued because of adverse side effects. The efficacy was assessed after 1 year on LTG. The mean follow‐up time was 2.8 years (range, 1.3–5.8).

Results: LTG had a favorable effect in 23 of 28 patients. A decrease in frequency of seizures of ≥50% was observed in 10 and a decrease in severity of seizures in nine of the 22 patients who had preceding seizures. Increases in well‐being were found in 18 of 28. During the follow‐up, LTG was continued as monotherapy in 13 of 19 patients.

Conclusions: In light of our experiences, LTG seems to be a valuable drug in JNCL.
Differential Cognitive Effects of Carbamazepine and Gabapentin
Authors: Meador K. J. , Loring D. W. , Ray P. G. , Murro A. M. , King D. W. , Nichols M. E. , Deer E. M. , Goff W. T.
Published: August 2005

Summary: Purpose: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain.

Methods: We directly compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in 35 healthy subjects by using a double‐blind, randomized crossover design with two 5‐week treatment periods. During each treatment condition, subjects received either GBP, 2,400 mg/day, or CBZ (mean, 731 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean, 8.3 μg/ml). Subjects were tested at the end of each AED treatment period and in four drug‐free conditions [two pretreatment baselines and two posttreatment washout periods (1 month after each AED)]. The neuropsychological test battery included 17 measures yielding 31 total variables.

Results: Direct comparison of the two AEDs revealed significantly better performance on eight variables for GBP, but none for CBZ. Comparison of CBZ and GBP to the nondrug average revealed significant statistical differences for 15 (48%) of 31 the variables. Pairwise follow‐up analyses of the 15 variables revealed significantly better performance for nondrug average on 13 variables compared with CBZ, and on four compared with GBP. GBP was better than nondrug average on one variable.

Conclusions: Although both CBZ and GBP produced some effects, GBP produced significantly fewer untoward cognitive effects compared with CBZ at the dosages used in this study.
Acute and Chronic Effects of Seizures in the Developing Brain: Lessons from Clinical Experience
Authors: Mizrahi Eli M.
Published: August 2005

Seizures in the neonate are often considered a form of status epilepticus (SE) because they are relatively prolonged, difficult to control with antiepileptic drugs (AEDs), and may be associated with significant morbidity and mortality. Despite their clinical importance, there is still no clear understanding of how seizures may affect the developing brain. Although both basic neuroscience and clinical research have addressed these issues, there are difficulties in the design and analysis of each type of investigation. Animal studies should reflect the human condition, the most relevant studies being those that consider neocortical rather than hippocampal seizures. Clinical investigations should be based on precise, age‐specific definitions of seizures of epileptic origin and of SE. Treatment strategies should be standardized with defined rationale and end points. Outcome measures are best when defined and quantifiable. The relative effects of underlying CNS injuries that coexist with the onset of neonatal seizures may be difficult to differentiate from the effects of the seizures themselves or their treatment. Current clinical studies suggest that the overriding factors in determining the outcome of neonates with seizures are the cause, the degree, and the distribution of brain injury at the time of seizure occurrence. However, such studies have limitations and may not yet employ methodology sensitive enough to detect a full range of adverse effects of seizures themselves.
Acute and Chronic Effects of Seizures in the Developing Brain: Experimental Models
Authors: Jensen Frances E.
Published: August 2005

Clinical experience suggests two major components to the relationship between brain development and epilepsy. First, the maturational state of the immature brain appears to generally decrease seizure threshold and contribute to a different seizure phenotype from the adult. Second, certain forms of seizures, when present during development, may modify brain maturation to result in chronic epilepsy and/or other neurocognitive deficits.

Maturational studies in animals suggest there are numerous factors developmentally regulated in such a way as to increase excitability in immature neuronal networks in the forebrain. The developing brain appears to exhibit a transient overexpression of glutamate receptors, glutamate receptor subunit composition permissive of enhanced excitatory neurotransmission, a relative lack of GABAergic inhibitory transmission, and ion channel expression and homeostasis which enhance neuronal excitability. The increased excitatory “drive” that is likely to be critical for normal brain development may share common mechanisms with those responsible for rendering the immature brain more susceptible to seizures, seizure induced plasticity (epileptogenesis), and neuronal injury. Furthermore, the coincidence of seizures during early postnatal brain development may modify many of these parameters, which in turn may promote long term epilepsy.
Pharmacology of Antiepileptic Drug Polypharmacy
Authors: Ferrendelli James A.
Published: August 2005

Therapeutic options for epilepsy are increasing, and all drugs can produce adverse side effects. Physicians should first use monotherapy when treating an epileptic patient. If one drug proves insufficient to control all seizures without intolerable side effects, then careful combination of the fewest drugs possible must be used. Combine drugs with different mechanisms of action rather than drugs with similar mechanisms of action. Closely monitor the patient for adverse side effects, which increase when multiple drugs are taken, and measure antiepileptic blood levels more frequently than with patients who are on monotherapy.
Gabapentin as Adjunctive Therapy for Partial Seizures
Authors: Bruni Joseph
Published: August 2005

The safety, tolerability, and efficacy of gabapentin as adjunctive therapy were assessed in epileptic patients who had experienced up to four complex partial seizures per month while receiving phenytoin and/or carbamazepine. This was a multicenter, open‐label prospective study, with the treatment period lasting 20 weeks. The gabapentin dosage was titrated to effective tolerated dose up to 2400 mg/day. Quality of life was evaluated with the QOLIE‐10 questionnaire. A total of 141 patients were enrolled; 114 patients were evaluated for efficacy analysis. The mean maintenance dose of gabapentin was 1600 mg/day. Seventy‐one percent of patients (81 patients) experienced a 50% or greater reduction in seizure frequency and 46% (52 patients) became seizure free. The most frequent adverse effects included drowsiness (16%), dizziness (9%), and asthenia (6%). Sixteen patients (11%) discontinued the study prematurely because of adverse events. A significant improvement was observed in five of the 10 questions of the QOLIE‐10.
Hypothalamic Neuronal Loss and Altered Circadian Rhythm of Temperature in a Rat Model of Mesial Temporal Lobe Epilepsy
Authors: Quigg Mark , Clayburn Hope , Straume Martin , Menaker Michael , Bertram Edward H.
Published: August 2005

Summary: Purpose: Numerous dysfunctions in endogenous hypothalamic function have been associated with mesial temporal lobe epilepsy (MTLE). One endogenous activity is the circadian rhythm of temperature (CRT). In this study we examined whether hypothalamically mediated function is altered in the electrically induced, self‐sustained, limbic status epilepticus model of MTLE. We then wished to determine whether there was a structural basis for regulatory alterations.

Methods: We measured CRT with peritoneal temperature telemetry obtained in light‐entrained (LD) and in free‐running, constant‐dark (DD) conditions. CRT from epileptic and controls of normal animals and kindled animals were quantized by fast Fourier transform‐nonlinear least squares analysis to determine rhythmic complexity.

Results: The circadian component of CRT was preserved in all animals. In DD, CRTs of epileptic animals were more complex than those of normal animals. CRT of kindled animals showed no increased complexity after electrically induced seizures. Neuronal density was decreased in regions of the anterior and posterior hypothalamus but not in the suprachiasmatic nuclei from the epileptic rats.

Conclusions: Alterations in CRT due to the epileptic state were independent of isolated seizures. Altered circadian thermoregulation in epileptic rats corresponded to regional hypothalamic neuronal loss. Structural changes of the hypothalamus may explain alterations in endogenous rhythms in MTLE.
Nonepileptic Seizures After Resective Epilepsy Surgery
Authors: Glosser Guila , Roberts Delight , Glosser David S.
Published: August 2005

Summary: Purpose: To identify factors that are associated with the emergence of nonepileptic seizures (NES) after resective epilepsy surgery.

Methods: Twenty‐two patients with medically refractory epilepsy in whom NESs were documented by EEG after resective surgery were compared with a larger series of epilepsy surgery patients on demographic, neurologic, and psychiatric variables.

Results: NES tended to become apparent in the first few months after surgery. Patients who developed NESs did not differ from other epilepsy surgery patients in terms of age, IQ, or preoperative psychiatric diagnoses. However, surgical NES patients’ neurologic problems and seizures began later in life, the NES group included a larger proportion of female subjects and patients with right hemisphere surgery, and NES patients were more likely to develop non‐NES psychiatric problems after surgery.

Conclusions: The heterogeneous collection of behaviors subsumed under the label NESs are determined by multiple factors. Several variables were found to be specifically associated with the development of NES after resective epilepsy surgery. A disproportionate number of postsurgical NES patients are female, they have primary neurologic dysfunction in the right hemisphere, and their epileptic seizures often began after adolescence. We propose that at least one group of patients with somatoform tendencies develop NESs as part of the psychiatric instability that occurs often in the few months after resective surgery.
Relation of Interictal Spike Frequency to 1H‐MRSI‐Measured NAA/Cr
Authors: Serles Wolfgang , Li Li Min , Caramanos Zografos , Arnold Douglas L. , Gotman Jean
Published: August 2005

Summary: Purpose: Whereas EEG spiking and decreases of the neuronal marker N‐acetyl‐aspartate (NAA) both localize well the epileptic focus, the significance of the intensity of these variables is unclear. Therefore we investigated whether the frequency of interictal surface spikes is related to the degree of N‐acetyl‐aspartate/creatine (NAA/Cr) ratio decrease as measured by proton magnetic resonance (MR) spectroscopic imaging (1H‐MRSI) in patients with intractable partial epilepsy.

Methods: We retrospectively studied 14 patients, nine with temporal lobe epilepsy and five with frontal lobe epilepsy. Spikes that occurred during prolonged video‐EEG monitoring from electrodes placed according to the International 10–20 system were counted blinded to the 1H‐MRSI results. Eight electrode positions (F3/4, C3/4, T3/4, T5/6) were assigned to underlying brain subregions in the 1H‐MRSI volume of interest. We converted NAA/Cr ratios into z‐scores (NAA/Crz) to compared NAA/Cr values directly across subregions. We calculated Spearman rank‐order (ρ) and Pearson product‐moment (r) correlations between spike frequency and NAA/Crz values overall, as well as within each brain subregion.

Results: We found an overall negative relation between spike‐frequency data and NAA/Crz data (ρ=−0.341). When analyzing only spiking subregions, this negative relation became slightly stronger (ρ=−0.442; r=−0.338). When data from the eight sites were considered separately, this negative relation remained in most instances.

Conclusions: Our results reveal a trend toward higher interictal spike frequencies on surface EEG in regions of pronounced neuronal metabolic damage or dysfunction. This suggests that both variables parallel an underlying pathologic substrate, although the pathophysiologic processes may be distinct.
Epidemiologic Study of Epilepsy in Young Singaporean Men
Authors: Kun Loh Ngai , Ling Lee Wei , Wah Yew Woon , Lian Tjia Tjoei
Published: August 2005

Summary: Purpose: This survey of 20,542 Singaporean men born in 1974 studied the clinical features of young men diagnosed with epilepsy on preenlistment screening.

Methods: All male citizens in Singapore are medically screened at age 18 years before enlistment for compulsory military service. Patients suspected to have epilepsy are then referred to government hospitals for further management. We interviewed the patients and their parents and reviewed their hospital records.

Results: Eighty‐nine patients with epilepsy were identified, indicating a lifetime prevalence of 4.9/1,000 males by age 18 years. The lifetime prevalence of epilepsy among Chinese, Malays, and Indians were 5.2, 2.8, and 6.4/1,000, respectively; these differences were not statistically significant. The mean age of seizure onset was 11.1 years. Generalized seizures (65.2%) were commoner than partial seizures (34.8%); common seizure types included generalized tonic‐clonic seizures (52.8%), complex partial seizures with secondary generalization (24.7%), and myoclonic seizures (5.6%). Common epileptic syndromes included temporal lobe epilepsy (16.9%), juvenile myoclonic epilepsy (5.6%), and frontal lobe epilepsy (2.2%). Eighty‐four (94.4%) patients sought medical treatment, and seven (7.9%) patients sought additional traditional treatment. Although 70 (78.7%) patients responded to medication, 14 (15.7%) patients remained refractory to treatment.

Conclusions: The lifetime prevalence of epilepsy in young Singaporean men was 4.9/1,000. The majority (65.2%) had generalized seizures. Temporal lobe epilepsy was the commonest (16.9%) defined epilepsy syndrome. More patients with epilepsy (94.4%) sought medical treatment, although 15.7% remained refractory to medication.
Longitudinal Follow‐Up in 145 Patients with Medically Refractory Temporal Lobe Epilepsy Treated Surgically Between 1984 and 1995
Authors: Salanova Vicenta , Markand Omkar , Worth Robert
Published: August 2005

Summary: Purpose: There are few studies of prolonged longitudinal follow‐up after temporal resections.

Methods: We analyzed 145 consecutive patients with temporal lobe epilepsy treated surgically. Patients had a comprehensive presurgical evaluation, including video‐EEG, psychometric testing, magnetic resonance imaging (MRI), single‐photon emission computed tomography (SPECT), intracarotid amobarbital procedure (IAP), and recently, volumetric head MRIs and F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) scans. Most had en bloc temporal resections, and a few had lesionectomies and resection of the epileptogenic zone. There was no surgical mortality. Longitudinal follow‐up data of the seizure outcome were analyzed by actuarial analysis. Patients were followed up at 6 weeks, 3 months, 6 months, and then on a yearly basis. The mean follow‐up was 5.6 years.

Results: Sixty‐six percent were seizure free at 1 year, 63% at 2 years, 60% at 5 years, and 55% at 10 years follow‐up. Moreover, 85%, became seizure free for ≤2 at the time of last follow‐up or had rare seizures. Patients who were seizure free for 1 and 2 years after surgery, had an 83% and 92% probability, respectively, of remaining seizure free at the time of last follow‐up. Ninety‐one percent of patients with small tumors and cavernous angiomas became seizure free compared with 69% of patients with hippocampal sclerosis.

Conclusions: Actuarial analysis showed that the long‐term surgical outcome of temporal lobe epilepsy remains favorable. Follow‐up at 1 and 2 years is highly predictive of the long‐term outcome. Patients with discrete lesions had the best outcome. Most of the patients with late recurrences had hippocampal sclerosis or temporal lobe gliosis. Some patients with postoperative seizures eventually became seizure free, reflecting the running‐down phenomenon.
Epileptic Spasms Preceded by Partial Seizures with a Close Temporal Association
Authors: Kubota Toshiko , Aso Kosaburo , Negoro Tamiko , Okumura Akihisa , Natsume Jun , Takada Hiroyuki , Itomi Kazuya , Watanabe Kazuyoshi , Yamamoto Naoki
Published: August 2005

Summary: Purpose: To investigate the distinctive features of patients with West syndrome who had partial seizures followed by epileptic spasms (PS‐ES).

Methods: We examined 45 patients with West syndrome whose epileptic spasms were recorded with simultaneous video‐electroencephalography (EEG) monitoring between 1982 and 1996. We investigated the patients who had PS‐ES and compared the PS‐ES patients with the 37 patients without PS‐ES.

Results: Of the 45 patients who had epileptic spasms in clusters (ES) and hypsarrhythmia on the interictal EEG, eight (17%) had ES preceded by partial seizures (PS) with a close temporal association. Seven of these eight were female patients. The underlying disorders were tuberous sclerosis (one patient), Aicardi syndrome (one), nonketotic hyperglycinemia (one), and focal cortical dysplasia (one). The etiology was unknown in the remaining four patients, but was suspected to be of prenatal origin in three. Three types of seizure sequence were identified: PS followed several seconds later by ES (two patients), alternating PS and ES starting with PS (three), and PS gradually replaced by ES with overlapping of the two (three). PS‐ES disappeared or was replaced by other types of seizures in 1–34 months. Six patients could not walk, and all patients could not speak any sentences at age 3 years.

Conclusions: Compared with patients without PS‐ES, those with PS‐ES more often had organic brain lesions of prenatal origin, other types of seizures before the onset of ES, asymmetric hypsarrhythmia on the EEG, and poor psychomotor outcome.
Slow Hyperpolarization in Cortical Neurons: A Possible Mechanism Behind Vagus Nerve Simulation Therapy for Refractory Epilepsy?
Authors: Zagon Aniko , Kemeny Andras A.
Published: August 2005

Summary: Purpose: Recent studies have shown that chronic, intermittent stimulation of the left vagus nerve (VNS) decreases the frequency, duration, and/or intensity of seizures in some patients with medically refractory focal seizures. Although VNS is being used in an increasing number of patients, the neuronal mechanism behind VNS therapy of refractory epileptic seizures is yet unclear.

Methods: In vivo intracellular recordings were used to study responses elicited by the VNS in pyramidal neurons of the parietal association cortex in anesthetized rats.

Results: Low‐intensity trains of VNS, which activated predominantly myelinated fibers (100 μA, 30 Hz, 0.5 millisecond, 20 seconds), elicited a slow hyperpolarization (onset latency 17.4 ± 2.0 seconds, amplitude –4.7 ± 0.6 mV, duration 35 ± 3.2 seconds; n = 19). Increasing the intensity of VNS to recruit nonmyelinated vagal fibers (200 μA) led to an increase in the magnitude of the response in some neurons while failed to evoke a response in others. On increasing the stimulus intensity to 500 μA, only one in nine neurons exhibited a visible response. All recorded and visualised neurons were pyramidal cells in cortical layer V.

Conclusions: Stimulus intensities that activate predominantly myelinated fibers (less than 200 μA) were most effective to induce slow vagal hyperpolarization. It is suggested that slow hyperpolarization may be one of the mechanisms that underlie the seizure‐reducing effect of VNS, by means of reducing the excitability in neurons that would be involved in propagation of seizure activity. As the balance of activity in myelinated and nonmyelinated primary vagal afferents influenced the effect of VNS stimulation, it is likely that the effect of VNS is modulated as changes occur in the underlying vagal tone.
Electro‐Oculography, Electroretinography, Visual Evoked Potentials, and Multifocal Electroretinography in Patients with Vigabatrin‐Attributed Visual Field Constriction
Authors: Harding G. F. A. , Wild J. M. , Robertson K. A. , Lawden M. C. , Betts T. A. , Barber C. , Barnes P. M. F.
Published: August 2005

Summary: Purpose: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin‐attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin.

Methods: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro‐oculography, and flash and pattern visual evoked potentials, was undertaken.

Results: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro‐oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30‐Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level.

Conclusion: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.
Slow‐Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Focal Cortical Dysplasia
Authors: Menkes Daniel L. , Gruenthal Michael
Published: August 2005

Summary: Purpose: To evaluate the effect of slow‐frequency repetitive transcranial magnetic stimulation (SF‐rTMS) on interictal epileptiform activity and seizure frequency in a patient with medically refractory partial seizures due to focal cortical dysplasia.

Methods: A 9‐cm circular coil was positioned over the area of cortical dysplasia. One hundred stimuli given at 0.5 Hz at 5% below motor threshold were given biweekly for four consecutive weeks. The EEG was recorded for 30 min before and after the first 100 stimuli. The number of seizures during the month of stimulation was compared with that of the month before stimulation.

Results: Stimulation was associated with a 70% reduction in the frequency of seizures and a 77% reduction in the frequency of interictal spikes. No seizures occurred during stimulation.

Conclusions: SF‐rTMS was safe and well tolerated in this patient. The reduction in seizures and interictal spikes associated with SF‐rTMS supports the concept of SF‐rTMS‐induced cortical inhibition.
MR Spectroscopy Shows Reduced Frontal Lobe Concentrations of N‐Acetyl Aspartate in Patients with Juvenile Myoclonic Epilepsy
Authors: Savic I. , Lekvall A. , Greitz D. , Helms G.
Published: August 2005

Summary: Purpose: Neuropsychological studies suggest frontal lobe dysfunctions in patients with juvenile myoclonic epilepsy (JME). In this study we investigated whether an underlying mechanism could be a regional neuronal damage not visible with structural magnetic resonance (MR), but detectable with magnetic resonance spectroscopy (MRS).

Methods: The study included 15 patients with JME and 10 matched healthy controls. Quantitative single voxel MRS was conducted at 1.5 Tesla by using a STEAM sequence (TR/TE/TM = 6,000/30/13.7 ms). The voxels were placed over the right cerebellum, right thalamus, and the prefrontal and occipital cortex. The quantitation included fitting of transmitter gain, and correction for partial volume of cerebrovascular fluid. LC‐Model was used for estimation of the absolute concentrations of total N‐acetyl aspartate (NAA), cholines, total creatine, and myoinositol.

Results: Patients with JME had significantly reduced prefrontal concentrations of NAA in relation to controls (9.1 ± 1.0 vs. 10.2 ± 0.8 mM; p = 0.031 after Bonferroni correction). The other regions showed normal NAA values, as did the other metabolites.

Conclusions: The observed reduction in NAA levels suggests a prefrontal neuronal lesion in patients with JME.
Childhood Epilepsy and Asthma: Changes in Behavior Problems Related to Gender and Change in Condition Severity
Authors: Austin Joan K. , Dunn David W. , Huster Gertrude A.
Published: August 2005

Summary: Purpose: We conducted a 4‐year follow‐up study of behavior problems in children with either epilepsy (n = 115) or asthma (n = 105) to identify changes in behavior problems as they were related to gender and change in condition severity. All children were between ages 8 and 13 years and had been diagnosed with their respective conditions for 1 year at entry into the study.

Methods: Behavior problems were measured by using the mother's rating on the Child Behavior Checklist. Baseline and follow‐up behavior problem scores were examined to see if significant changes occurred over the observation period of the study. To explore change in behavior based on condition severity, each child was placed into “low” and “high” condition severity groups at each time, resulting in four groups: low/low, low/high, high/low, or high/high. There were too few cases in the low/high group to be included in some analyses. Data were analyzed by using analysis of covariance with adjustment for baseline behaviors, age, and age of onset.

Results: Within both samples, there was a significant improvement over time for the Total Behavior Problems and Internalizing Problems scores (p 0.006). Improvement in Internalizing Problems was greater for the asthma sample than for the epilepsy sample (p 0.007). Within the epilepsy sample, there was a significant gender‐by‐change in seizure condition interaction for Total Behavior Problems, Internalizing Problems, and Externalizing Problems. The interaction effect indicated that behavior problems in girls with high seizure severity at both baseline and follow‐up became substantially worse over the 4‐year period.

Conclusions: It was concluded that adolescent girls, particularly those with high‐severity epilepsy during the transition to adolescence, merit closer clinical supervision for behavior problems.
Acute Encephalopathy Associated with Vigabatrin in a Six‐Month‐Old Girl
Authors: Haas‐Lude K. , Wolff M. , Riethmüller J. , Niemann G. , Krägeloh‐Mann I.
Published: August 2005

Summary: Purpose: Vigabatrin (VGB) is a new‐generation anticonvulsant used in the treatment of partial seizures and West syndrome. Side effects of VGB treatment in adults and children are well described. Acute encephalopathy with VGB has recently been reported in eight adults. They developed stupor, confusion, and electroencephalographic abnormalities after starting VGB. Does the acute encephalopathy with VGB also occur in childhood?

Methods: We describe a 6‐month‐old girl with infantile Alexander disease with hydrocephalus who developed similar clinical symptoms with apathia, somnolence, and sopor, as well as slowing of the background activity in EEG, 3 days after starting VGB. After exclusion of shunt dysfunction, encephalitis, metabolic dysfunction, and renal failure, VGB was discontinued.

Results: During the next 2 days, symptoms subsided, and after 10 days, EEG background activity returned to the one before starting VGB.

Conclusions: Acute encephalopathy associated with VGB in children seems to be very rare, but should not be ignored.
In Vitro Model of Epileptiform Electrical Activity in Kainate‐ Treated Organotypic Hippocampal Slices
Authors: Starkey Sarah J. , Hagan Russell M. , Xie Xinmin M.
Published: August 2005

Summary: Rationale: Administration of kainate to rodents in vivo produces temporal lobe lesions, followed several weeks later by the development of delayed spontaneous recurrent motor seizures (Cavalheiro et al. Electroencephalogr. Clin. Neurophysiol. 1982;53:581). Cell loss also occurs following kainate administration to hippocampal slices (Best et al., Eur. J. Neurosci. 1996;8:2109). The present study investigated whether kainate applied in vitro produces subsequent chronic spontaneous epileptiform electrical activity. Methods: Hippocampal slices (400 mM thick; P9 neonatal rats) were cultured (Stoppini et al., J. Neurosci. Methods 1991;37:173) for 5–7 weeks. Organotypic slices were exposed to 5 mM kainate for 24 h, 3 weeks post‐cutting and extracellular electrophysiological recordings made 2–3 weeks post‐kainate treatment. Results: Propidium iodide revealed cell death, particularly in CA3, in response to the kainate. Spontaneous interictal (short spontaneous bursts 96 ± 20A ms duration, n = 7) and/or “ictal” (long spontaneous bursting, ranging from 120 s to continuous, n = 10) electrical activity was detected in CA1 of all kainate‐treated slices. Very little or no spontaneous discharges were detected in control slices (n = 12). Both forms of activity were completely inhibited by the Na channel blocker tetrodotoxin (0.1 mM, n = 3). Interictal activity was completely inhibited by the anticonvulsant lamotrigine (IC50= 51 mM, 28–91 mM, 95% confidence limits, n = 3). However, lamotrigine had no effect on the “ictal” activity (up to 300 mM, n = 3). Discussion: Chronic spontaneous interictal and/or “ictal” epileptiform activity was detected 2–3 weeks following kainate‐induced cell loss in cultured hippocampal slices. Pharmacological characterization of the electrical discharges and the potential refractoriness of the “ictal” activity are currently under investigation.
Effects of Gabapentin on Brain GABA, Homocarnosine, and Pyrrolidinone in Epilepsy Patients
Authors: Petroff Ognen A. C. , Hyder Fahmeed , Rothman Douglas L. , Mattson Richard H.
Published: August 2005

Summary: Purpose: Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain γ‐aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, homocarnosine and pyrrolidinone, increase in response to the first dose of GBP.

Methods: In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14‐cc volume in the occipital cortex by using a 1H spectroscopy with a 2.1‐Tesla magnetic resonance spectrometer and an 8‐cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200–2,000 mg) of GBP were rechal‐lenged with a single high dose (2,400 mg).

Results: The first dose of GBP increased median brain GABA by 1.3 mM (range, 0.4–1.8 mM) within 1 h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 mM;95% CI, 0.2–0.9), homocarnosine (0.3 mM; 95% CI, 0.2–0.4), and pyrrolidinone (0.10 mM; 95% CI, 0.06–0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 mM (range, 0.3–0.5) within 1 h.

Conclusions: GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased homocarnosine and pyrrolidinone with daily therapy.
Sleep and Epilepsy: A Key Role for Nitric Oxide?
Authors: Faradji H. , Rousset C. , Debilly G. , Vergnes M. , Cespuglio R.
Published: August 2005

Summary: Purpose: It has been suggested that nitric oxide (NO) is involved in sleep mechanisms and in the pathophysiology of epilepsy. Data are, however, controversial because it is not clear whether NO facilitates sleep or waking, or whether it exerts pro‐ or antiepileptic influences.

Methods: The question was considered through NO voltammetric measurements and electroencephalographic recordings performed in GAERS rats (Genetic Absence Epilepsy Rat from Strasbourg): an experimental model of “petit‐mal” human disease. Regulatory processes of sleep and epilepsy were studied after administration of a NO synthase inhibitor [l‐arginine‐p‐nitroanilide (lANA) 100 mg/kg i.p.], a NO donor (SIN‐1 100 ng/2 μl i.c.v.), and the antiepileptic drugs used in clinic [valproate (VPA 200 mg/kg i.p.) and ethosuximide (ESM 100 mg/kg i.p.)].

Results: In GAERS rats, spontaneous circadian organizations of spike‐wave discharges and paradoxical sleep (PS) occur in an opposite way; spontaneous NO concentrations are higher during seizures than during wakefulness, slow‐wave sleep, and PS, respectively. lANA induces a disappearance of NO peak, an epileptic induction, and a loss of PS while SIN‐1 induces opposite effects. Antiepileptic effects of VPA and ESM are associated with a PS increase and a significant release of NO.

Conclusions: These results indicate that NO could be, in GAERS rats, a central piece in the reciprocal inhibitory mechanisms regulating the induction of PS and spike‐wave discharges. NO could prevent absence epilepsy and act as an antiepileptic substance in facilitating PS. Antiepileptic efficiency of VPA and ESM may work through their ability to release NO. A track for a new treatment of petit‐mal disease in children can be envisioned.
Body Dimensions of Infants Exposed to Antiepileptic Drugs In Utero: Observations Spanning 25 Years
Authors: Wide K. , Winbladh B. , Tomson T. , Källén B.
Published: August 2005

Summary: Purpose: To investigate the influence of maternal antiepileptic drug (AED) treatment on pregnancy duration, birth weight, body length, head circumference, and intrauterine growth in infants exposed in utero to antiepileptic drugs in Sweden between 1973–1997, with 963 singleton infants.

Methods: Data collected from (a) 1973–1981 (record linkage between a hospital discharge register and a medical birth register); (b) 1984–1995 (prospectively collected information in one defined catchment area with two delivery hospitals); and (c) 1995–1997 (medical birth register data). Observed numbers of infants below a defined size for body measurements compared with expected numbers calculated from all births in Sweden after stratification for year of birth, maternal age, parity, and education or smoking habits in early pregnancy. Standard deviation scores estimated with same stratification procedures.

Results: Fraction of monotherapy exposures increased from −40% to −90% from 1973 to 1997. Significantly increased numbers of infants with small body measurements found in exposed group. Negative influence on body dimensions decreased over time. More marked effects found in infants exposed to polytherapy. In monotherapy, only infants exposed to carbamazepine consistently showed reduction in body dimensions. Significant effect on gestational age in girls and on number of small for gestational age (<2 SD) in boys.

Conclusions: Polytherapy with antiepileptic drugs and negative influence on body dimensions decreased. In monotherapy, only carbamazepine has a negative influence on body dimensions in this study.
Topiramate in Refractory Epilepsy: A Prospective Observational Study
Authors: Stephen Linda J. , Sills Graeme J. , Brodie Martin J.
Published: August 2005

Summary: Purpose: This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic.

Methods: One hundred seventy patients (82 men, 88 women, aged 18–75 years) with refractory localization‐related (n = 134) or idiopathic generalized epilepsy (n = 36) were started on adjunctive TPM using a standard titration schedule. TPM was introduced after a 3‐month prospective baseline, and doses were adjusted according to clinical response. End points were seizure freedom for 6 months, 50% seizure reduction for 6 months compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both.

Results: Thirty‐nine (23%) patients were seizure‐free, and 80 (47%) more patients had a useful therapeutic response. Thirteen seizure‐free patients and 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 51 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure‐free. Final TPM doses and concentrations varied widely among the three outcome groups.

Conclusions: TPM was efficacious as add‐on and mono‐therapy in patients with refractory partial and generalized seizures in everyday clinical use. A good response was obtained in many patients with TPM doses substantially lower than those studied in regulatory clinical trials. The wide variation in dose‐response and dose‐toxicity relationships may reflect different neurobiologies causing refractory epilepsy and differential efficacy of AED combinations.
Newly Diagnosed Epilepsy: Can Nurse Specialists Help? A Randomized Controlled Trial
Authors: Ridsdale L. , Kwan I. , Cryer C. ,   and the Epilepsy Care Evaluation Group
Published: August 2005

Summary: Purpose: To describe a group of people with newly diagnosed epilepsy and to test the effect of an epilepsy nurse specialist on patients' knowledge of epilepsy, satisfaction with the advice provided, and psychological well‐being.

Methods: Neurologists in the United Kingdom (U.K.) recruited adults with newly diagnosed epilepsy. Patients were randomized to receive the offer of two appointments with an epilepsy nurse specialist or usual medical care. The main outcome measures were a questionnaire assessing patients' knowledge of epilepsy, the Hospital Anxiety and Depression Scale, and patients' reported satisfaction with the advice and explanations provided on key epilepsy‐related topics.

Results: Ninety people with new epilepsy completed the trial. At baseline, fewer than half the patients reported having been given enough advice on epilepsy, and there were important differences in patients' knowledge of epilepsy. Lack of a U.K. school‐leaving examination pass (General Certificate School Examination) was associated with lower knowledge of epilepsy (p = 0.03). At follow‐up, the patients randomized to see the nurse specialist were significantly more likely to report that enough advice had been provided on most epilepsy‐related topics compared with the control group. There were no significant differences in knowledge of epilepsy scores. However, there were significant differences in the group who, at baseline, had knowledge scores in the lowest quartile; those randomized to the nurse had higher knowledge scores (42.7 vs. 37.2; p < 0.01). Compared with doctors, the nurse was highly rated for providing clear explanations.

Conclusions: Patients who have less general education have less knowledge of epilepsy. The introduction of a nurse specialist in epilepsy is associated with a significant increase in patient reports that enough advice has been provided. Nurse intervention appears to help those with the least knowledge of epilepsy improve their knowledge scores.
Early and Late Intracortical Inhibition in Juvenile Myoclonic Epilepsy
Authors: Manganotti Paolo , Bongiovanni Luigi Giuseppe , Zanette Gianpietro , Fiaschi Antonio
Published: August 2005

Summary: Purpose: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy.

Methods: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIs) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits.

Results: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age‐matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period.

Conclusions: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.
Risk of Epilepsy in Long‐Term Survivors of Surgery for Aneurysmal Subarachnoid Hemorrhage: A Population‐Based Study in Iceland
Authors: Olafsson Elias , Gudmundsson Gunnar , Hauser W. Allen
Published: August 2005

Summary: Purpose: Epilepsy is known to result from aneurysmal subarachnoid hemorrhage (SAH). There are no population‐based estimates of the absolute risk or the duration for which this risk is elevated. We have conducted a population‐based study in Iceland of the risk of epilepsy after a ruptured cerebral aneurysm to address these questions.

Methods: The index patients are all of the patients who presented with SAH caused by ruptured cerebral aneurysm in Iceland during an 11‐year period (1958 to 1968) and survived more than 6 months. We determined the number of index patients who developed epilepsy. The observed number of cases of epilepsy was compared with that expected based on the incidence of epilepsy in Iceland.

Results: There were 44 index patients; 11 (25%) developed epilepsy, all within 4 years of the insult. Seven (70%) of 10 patients with acute symptomatic seizures (defined as seizures during the first 2 weeks after the hemorrhage) developed epilepsy (relative risk, 7.0; 95% confidence interval, 2.3–21.6). Epilepsy was more frequent in patients with severe neurological residua (48%) compared with patients without (20%) (relative risk, 2.5; 95% confidence interval, 0.9–6.3).

Conclusions: The risk for epilepsy among survivors of SAH caused by ruptured cerebral aneurysm is substantially increased. Both acute symptomatic seizure and persistent neurological impairment are associated with a further increase in the risk of epilepsy.
Cost Evaluations in Epilepsy: An Update
Authors: Langfitt John T.
Published: August 2005

Summary:The purpose of this article is to describe the developments in the methodology of studies of the cost of epilepsy and cost‐effectiveness of treatments in light of previous reviews and recently published methodological guidelines. Several recent studies are compared, with recently published guidelines by the US Public Health Service (PHS) serving as a framework for discussing selected methodological issues. Results show that these recent studies have made important gains in the quality of cost data obtained, with advances being made by studies that base cost estimates on actual patient data from representative samples as opposed to secondary sources and expert opinions. However, a wide variety of methods continue to be used for many aspects of study design and reporting. Method heterogeneity remains an obstacle to presenting and interpreting reliable and valid information on costs and cost‐effectiveness. Areas in need of additional development are methods for estimating direct nonmedical costs, attributing costs to epilepsy versus comorbid conditions, validating health state valuation methods for this population, and validating current recommendations for capturing the costs of lost productivity due to epilepsy. PHS panel recommendations provide a useful framework for working toward consistency in the methods for economic studies in epilepsy.
Glutamate Receptor Activation in the Kindled Dentate Gyrus
Authors: Behr Joachim , Heinemann Uwe , Mody Istvan
Published: August 2005

Summary: Purpose: The contribution of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), N‐methyl‐d‐aspartate (NMDA), and kainate receptor activation to the enhanced seizure susceptibility of the dentate gyrus was investigated in an experimental model of temporal lobe epilepsy.

Methods: Using the specific NMDA and AMPA receptor antagonists D‐APV and SYM 2206, we examined alterations in glutamate receptor‐dependent synaptic currents 48 hours and 28 days after kindling in field‐potential and voltage‐clamp recordings.

Results: Forty‐eight hours after kindling, the fractions of AMPA and NMDA receptor‐mediated excitatory postsynaptic current components shifted dramatically in favor of the NMDA receptor‐mediated response. Four weeks after kindling, however, AMPA and NMDA receptor‐mediated excitatory postsynaptic currents reverted to control‐like values. Neither single nor repetitive perforant path stimuli evoked kainate receptor‐mediated excitatory postsynaptic currents in dentate gyrus granule cells of control or kindled rats.

Conclusion: The enhanced excitability of the kindled dentate gyrus 48 hours after the last seizure most likely results from transiently enhanced NMDA receptor activation. The NMDA receptor seems to play a critical role in the induction of the kindled state rather than in the persistence of the enhanced seizure susceptibility.