bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Ex Vivo Magnetic Resonance Imaging to Detect Onset of Vigabatrin‐Induced Intramyelinic Edema in Canine Brain
Authors: Peyster R. G. , Sussman N. M. , Hershey B. L. , Heydorn W. E. , Meyerson L. R. , Yarrington J. T. , Gibson J. P.
Published: August 2005

Summary: Vigabatrin (VGB) causes intramyelinic edema (micro vacuolation) in brain of dogs and rodent, which has encouraged development of noninvasive methods to monitor for this effect during clinical trials. We report the qualitative ex vivo magnetic resonance imaging (MRI) changes observed in a neuropathology study in dogs to detect time of onset and regression of VGB‐induced intramyelinic edema. Beagles were randomly assigned to 18 groups of 6 dogs per group and administered vigabatrin orally (p.o.) at a dose of 300 mg/kg/day (2 males, 2 females) or placebo (1 male, 1 female). Animals were killed and examined at weekly intervals during the 12 weeks of treatment and at 1, 2, 4, 8, 12, and 16 weeks after discontinuation of drug treatment. Myelin microvacuolation in thalamus, hypothalamus, and fornix were noted histologically after 4–5 weeks of treatment. Increases in MRI T2 intensity were observed in hypothalamus after 4 weeks and in thalamus and columns of the fornix after 7 weeks. Both MRI T2 intensity and microvacuolation continued to increase during 12‐week VGB treatment. When VGB treatment was discontinued after 12 weeks, both MRI T2 intensity and microvacuolation began to decrease. Six‐teen weeks after VGB discontinuation, histopathology had returned to normal and MRI examination demonstrated a marked trend toward reversal of the increased T2 signal intensity. MRI thus has potential as a noninvasive surveillance technique in certain experimental and clinical conditions associated with intramyelinic edema.
Interictal Temporal Hypoperfusion Is Related to Early‐Onset Temporal Lobe Epilepsy
Authors: Duncan Roderick , Patterson James , Hadley Donald , Roberts Richard , Bone Ian
Published: August 2005

Previous studies of interictal regional cerebral blood flow (rCBF) in temporal lobe epilepsy have shown variable correlations with clinical measures. We used high spatial resolution hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO SPECT) in 80 consecutive patients with complex partial seizures (CPS), comparing results with those from a large series of normal subjects. Visual image analysis detected abnormalities of rCBF in 41 of 80 (51%; numeric analysis detected abnormalities in 38 of 80). Age at epilepsy onset was significantly younger in patients with temporal hypoperfusion (p = 0.002), and the frequency distribution of hypoperfusion versus age at epilepsy onset was reverse exponential. The results of numerical image analysis showed that degree of hypoperfusion did not vary with age at epilepsy onset. These data suggest a single insult operating early in life as a cause of temporal hypoperfusion, as has been shown for mesial temporal sclerosis (MTS). We could not demonstrate relationships with other clinical variables, including time since last seizure.
Weeping During Psychogenic Nonepileptic Seizures
Authors: Walczak Thaddeus S. , Bogolioubov Alexei
Published: August 2005

Ictal weeping may help distinguish psychogenic nonepileptic seizures (PNES) from epileptic seizures. However, the prevalence of weeping during PNES or epileptic seizures is unknown. We reviewed videotapes of recorded events in 84 consecutive patients with PNES or epilepsy. Weeping was observed during 14% of PNES in 31% of patients with PNES. Ictal weeping was not observed in any epileptic seizures occurring in 48 patients. The differences were highly significant. One patient with epileptic seizures originating in the right temporal lobe wept soon after the end of a seizure. Depression was not more common in PNES patients with than without ictal weeping. Weeping during an apparent seizure strongly argues that the event is not epileptic.
Two Patients with Juvenile Myoclonic Epilepsy and Nonconvulsive Status Epilepticus
Authors: Kimura Seiji , Kobayashi Takuya
Published: August 2005

We report 2 girls, aged 10 and 13 years, with juvenile myoclonic epilepsy (JME) who had episodes of nonconvulsive status epilepticus (NCSE). Symptoms included only mild lethargy, slow responses, and trembling of the eyelids. There was no ataxia or myoclonus of the limbs or body, and they were always able to respond. Electroencephalograms during these episodes showed almost continuous generalized polyspike‐waves in both patients. Patients with JME can develop NCSE, which may be overlooked because of the subtle clinical symptoms.
Cutis Verticis Gyrata—Mental Deficiency Syndrome: A Patient with Drug‐Resistant Epilepsy and Polymicrogyria
Authors: Striano Salvatore , Ruosi Patrizia , Guzzetta Vito , Perone Lucia , Manto Andrea , Cirillo Sossio
Published: August 2005

We report a case of cutis verticis gyrate‐mental deficiency syndrome (CVG‐MD) which was associated with drug‐resistant epilepsy and bilateral occipital polymicrogyria. Genetic analysis showed an increased number of breaks at the 3p14 and 16q23 sites. We hypothesize that a deleterious factor acting at a critical period of intrauterine development could result in the cerebral malformation and in the development of CVG. Neuroradiological investigation is warranted in cases of CVG‐MD.
Predictors of Outcome of Epilepsy Surgery: Multivariate Analysis with Validation
Authors: Armon Carmel , Radtke Rodney A. , Friedman Allan H. , Dawson Deborah V.
Published: August 2005

Summary: Purpose: To identify predictors of outcome of epilepsy surgery, using the Duke experience, applying multivariate analysis and validation techniques. To compare the results of different modeling algorithms. Few previous studies have reported multivariate analysis, or validated their results.

Methods: Records of 116 patients with focal resections for intractable epilepsy from January 1, 1980 through June 30, 1989 were analyzed. Primary outcome variable was patient's condition in second postoperative year: seizure free (except auras), or not. Three predictors of biologic interest were specified a priori for confirmatory analysis. Additional predictors were considered within exploratory analysis. Logistic regression techniques were applied to assess relations with pre‐and postoperative predictors. Internal validity was assessed by repeated random selection of training and validation samples, used in conjunction with bootstrap techniques.

Results: By using multivariate analysis, percentage of epileptic EEG activity arising from the site of resection and either imaging localization or lack of use of invasive monitoring were the only statistically significant preoperative predictors for good outcome at 2 years. Presence of seizures'within 2. months of surgery was a significant postoperative predictor for a poor outcome. Adding more variables did not result in significantly improved models. Use of validation techniques reduced the degree of optimism in the predictive value of the models.

Conclusions: Pooling of data from multiple institutions is needed to attain the large sample sizes needed for multivariate analysis with validation.
Reproduction Among Individuals with Idiopathic/Cryptogenic Epilepsy: Risk Factors for Reduced Fertility in Marriage
Authors: Schupf Nicole , Ottman Ruth
Published: August 2005

Summary: Purpose: We wished to determine risk factors for reduced fertility in marriage in men and women with idiopathic/cryptogenic epilepsy and to relate rates of reproduction to the risk of epilepsy in offspring of affected individuals.

Methods: We determined history of pregnancy and child bearing among 863 adults with idiopathic/cryptogenic epilepsy (ascertained from voluntary organizations) who had been married at some time in their lives and from their same‐sex siblings without epilepsy who had been married. We examined the effects of seizure type, age at onset, and family history of epilepsy on fertility. Fertility rates were measured as live births per person‐year of marriage before and after onset of epilepsy and compared with fertility rates among same‐sex siblings without epilepsy by incidence rate ratios (IRR).

Results: For both men and women with epilepsy, reduced fertility was observed after, but not before, onset of epilepsy: Among both men and women with epilepsy, those with partial onset and early age at onset (<10 years) were more reproductively disadvantaged than those with generalized onset and later age at onset. Among those with epilepsy, men with a family history of epilepsy were less reproductively disadvantaged than men without a family history of epilepsy, whereas women with and without a family history of epilepsy did not differ.

Conclusions: We found no evidence of selectively reduced fertility among men with a genetic susceptibility to epilepsy that could account for the higher risk of epilepsy among offspring of affected women than among offspring of affected men.
Characteristics of Seizures in a Population‐Based Series of Mentally Retarded Children with Active Epilepsy
Authors: Steffenburg Ulf , Hagberg Gudrun , Kyllerman Mårten
Published: August 2005

Summary: Purpose: The characteristics of seizures were analysed in a population‐based study of active epilepsy in 6‐to 13‐year‐old mentally retarded children.

Methods: The search procedure included diagnostic registers, EEG registers, and registers of the Education of the Subnormal. Medical files were scrutinized, and clinical examinations and interviews with parents or caretakers or both were performed.

Results: The median age of seizure onset was 1·3 years, 3·1 for children with mild retardation and 0·8 for children with severe retardation. Among the 98 children identified, current seizure groups were partial in 20, generalized in 59, and mixed in 19. The prevailing seizure types were tonic‐clonic, myoclonic, atypical absences, and partial complex seizures, present in 42, 33, 23, and 23 children, respectively. A total of 46 children had more than one seizure type. Seizures every day/week occurred in 44 children. There was a constancy between seizure type at onset and later seizure type. Neonatal seizures (n = 25), infantile spasms (n = 12), and status epilepticus (n = 37) occurred independent of one another. Prognostic factors for poor neurologic outcome were early onset of epilepsy, infantile spasms as onset type, and prior neonatal seizures. Children with only partial seizures less frequently had severe mental retardation, cerebral palsy, and visual impairment than those with only generalized seizures.

Conclusions: Epilepsies in children with mental retardation are characterized by severe seizure manifestations. The brain damage giving rise to mental retardation and epilepsy is probably the main factor in terms of seizure outcome.
Regional Increases in Brain‐Derived Neurotrophic Factor and Nerve Growth Factor mRNAs During Amygdaloid Kindling, But Not in Acidic and Basic Fibroblast Growth Factor mRNAs
Authors: Sato K. , Kashihara K. , Morimoto K. , Hayabara T.
Published: August 2005

Summary: We studied mRNA levels for neurotrophic factors using the amygdaloid kindling model of epilepsy. One hour after stage 5 kindled seizures, there were four‐to fivefold increases in brain‐derived neurotrophic factor (BDNF) mRNA in rat dentate gyrus and perirhinal cortex. Nerve growth factor (NGF) mRNA levels were increased bilaterally in some (but not all) limbic areas. There were no detectable changes in acidic fibroblast GF (aFGF) mRNA or basic fibroblast GF (bFGF) mRNA for 24 h after the kindled seizures. During kindling, levels of BDNF mRNA in the dentate gyrus correlated with projection to generalized seizures, whereas NGF mRNA in the limbic regions continued to increase during seizure development. These results indicate that the induction of mRNAs for neurotrophic factors, especially for BDNF mRNA in the dentate gyrus, corresponds to the increases in metabolic and electrical ictal discharge associated with kindled seizures. The persistent increase observed in NGF mRNA may be related to enhanced synaptic efficacy during kindling, but aFGF and bFGF are presumed to have little relation to the kindling process.
Predictors of Intractable Epilepsy in Childhood: A Case‐Control Study
Authors: Berg Anne T. , Levy Susan R. , Novotny Edward J. , Shinnar Shlomo
Published: August 2005

Summary: Little is known about what factors predict intractable epilepsy at the time of initial diagnosis. We performed a case‐control study to identify early predictors of medically intractable epilepsy in children. Cases were children who had an average of one seizure or more a month over a 2‐year period and who, during that time, had failed trials of at least three different antiepileptic drugs (AEDs). Controls were children who had epilepsy, who had been seizure‐free for 2 years, and who had never, before becoming seizure‐free, met the definition for intractable epilepsy. Strong univariate associations were noted between intractability and several factors: infantile spasms (IS) remote symptomatic epilepsy, a history of status epilepticus (SE) before the diagnosis of epilepsy, neonatal seizures, and microcephaly. Cases were significantly younger than controls at onset (1.8 vs. 5.8 years); this was not due solely to cases with onset during the first year of life but was an association apparent throughout the age range studied. With multiple logistic regression, independent predictors of intractability were IS, odds ratio (OR) = 10.42, p = 0.03; age at onset with a decreasing risk with increasing age, OR = 0.77 per year, p < 0.0001; remote symptomatic epilepsy, OR = 2.24, p = 0.04; and SE, OR = 3.30, p = 0.04. These findings complement those of recent cohort studies of remission of epilepsy and provide useful leads for future prospective studies of intractable epilepsy.
Behavioral Side Effects of Gabapentin in Children
Authors: Lee D. O. , Steingard R. J. , Cesena M. , Helmers S. L. , Riviello J. J. , Mikati M. A.
Published: August 2005

Summary: We report 7 children who received gabapentin (GBP) as adjunctive medication and subsequently developed behavioral side effects. These behavioral changes consisted of intensification of baseline behaviors as well as new behavioral problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioral changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder and developmental delays.
Phenytoin‐Induced Pseudolymphoma: Reevaluation Using Modern Molecular Biology Techniques
Authors: Jeng Yung‐Ming , Tien Hwei‐Fan , Su Ih‐Jen
Published: August 2005

Summary: Patients receiving phenytoin (PHT) may develop pseudolymphoma or, rarely, malignant lymphoma. Previously, distinguishing the two diseases based solely on histopathology has been difficult. The recent introduction of molecular biological techniques has provided a powerful tool to reassess this problem. A 17‐year‐old girl developed systemic lymphadenopathy after receiving PHT for 1 year for generalized tonic‐clonic seizures (GTCS). Biopsy of a cervical lymph node showed diffuse proliferation of large lymphoid cells mimicking a large cell lymphoma. Immunophenotypic, immunoglobulin gene rearrangement, and cytogenetic studies, however, showed polyclonal B‐cell proliferation, consistent with PHT‐induced pseudolymphoma. After PHT discontinuation, lymphadenopathy resolved in 1 month and no recurrence developed in the subsequent 10 months. Obtaining a history of drug use is crucial to recognizing this group of patients. Molecular biology and chromosome studies have become the definitive basis differentiating pseudolymphoma from malignant lymphoma in patients receiving chronic PHT therapy.
Empirical Techniques for Determining the Reliability, Magnitude, and Pattern of Neuropsychological Change After Epilepsy Surgery
Authors: Hermann Bruce P. , Seidenberg Michael , Schoenfeld Jen , Peterson Jacqueline , Leveroni Catherine , Wyler Allen R.
Published: August 2005

Summary: Purpose: We assessed test‐retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression‐based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy.

Methods: Forty patients with complex partial seizures (CPS) who did not undergo epilepsy surgery were administered a comprehensive neuropsychological battery on two. occasions. Their test‐retest data were used to compute both RCIs and regression‐based norms for change for each neuropsychological index. RCIs corrected for practice effects provide a confidence interval (CI) indicating the degree of performance change required to exceed the variability attributable to sources of error (e.g., practice, test‐retest reliability). Regression‐based norms for change also correct for several sources of measurement measurement error and examine observed versus expected test‐retest changes on a common metric, thereby facilitating determination of the degree and relative magnitude of change across cognitive domains.

Results: Mean changes in test‐retest performance were generally modest, but were evident across several test measures. Our data indicate a considerable degree of individual variability in test‐retest Performance.

Conclusions: RCIs and regression‐based norms are complementary indexes and can be particularly useful in examining the test‐retest performance of individual patients who undergo epilepsy surgery as well as in the more general investigation of cognitive outcome after epilepsy surgery.
Incidence of Epilepsy in Rural Iceland: A Population‐Based Study
Authors: Olafsson Elías , Hauser W. Allen , Ludvigsson Pétur , Gudmundsson Gunnar
Published: August 2005

Summary: Purpose: We wished to determine the incidence of epilepsy in the population of rural Iceland.

Methods: Cases were identified through review of records of primary care facilities for the study population, supplemented by review of referrals to EEG facilities and neurologic specialists.

Results: The incidence of epilepsy (recurrent unprovoked seizures) was 47 in 100,000. Age‐specific incidence was bimodal, highest in the youngest and oldest age groups. About one third of the patients had an identifiable etiology, and one third had partial seizures. Integration of imaging and neurophysiologic data did little to modify the distribution of etiology or seizure type.

Conclusions: The present study confirms findings of other recent studies of incidence in Western Countries.
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy: Electroclinical Picture
Authors: Oldani Alessandro , Zucconi Marco , Ferini‐Strambi Luigi , Bizzozero Daniele , Smirne Salvatore
Published: August 2005

Summary: Purpose: Nocturnal frontal lobe epilepsy is a disorder that is difficult to diagnose because its clinical presentation is often limited to motor behavior during sleep. For this reason, a misleading diagnosis of benign nocturnal parasomnias might be possible. Recently, an inherited form of nocturnal frontal lobe epilepsy was described in some families. The aim of our work was to describe the electroclinical pattern of a sample of familial cases with this syndrome.

Methods: We observed 33 patients, all complaining of frequent nocturnal motor attacks, from eight Italian families. The family trees were strongly supportive of autosomal dominant inheritance. We performed a full‐night video‐polysomnographic monitoring in 12 patients.

Results: The recordings showed attacks in all patients, there being a widespread pattern of motor activity. Ictal and interictal EEG abnormalities were often hidden and, unless associated with a video recording, were of no use for the final diagnosis. Intraindividual stereotypy, abrupt onset, and semiology of attacks allowed differentiation from healthy subjects’nocturnal motor behavior.

Conclusions: Autosomal dominant nocturnal frontal lobe epilepsy is probably not uncommon. Full‐night video‐polysomnographic monitoring is fundamental for the differential diagnosis of benign parasomnias and, consequently, for appropriate therapy.
The Ictal Bradycardia Syndrome
Authors: Reeves Andrew L. , Nollet Kenneth E. , Klass Donald W. , Sharbrough Frank W. , So Elson L.
Published: August 2005

: Purpose: Episodic loss of consciousness presents a diagnostic challenge to the neurologist. A perhaps under‐recognized cause of episodic loss of consciousness, which we call the ictal bradycardia syndrome, occurs when epileptic discharges profoundly disrupt normal cardiac rhythm, resulting in cardiogenic syncope during the ictal event. We attempt to determine whether the presence of the ictal bradycardia syndrome provides localizing information regarding the site of seizure onset and to describe the demographics of patients with this syndrome. We also discuss difficulties in diagnosis and treatment.

Methods: We review 23 cases of the ictal bradycardia syndrome from the literature and present four additional cases. Brief histories are provided for the four previously unreported cases. Where data are available, cases are analyzed with respect to age, sex, and site of seizure onset.

Results: Patients with the ictal bradycardia syndrome ranged from 4 months to 72 years (mean 39 years). There was an approximately 5:1 ratio of males to females. Twenty of the 23 patients (87%) whose site of ictal onset could be localized had temporal lobe epilepsy, although no clear lateralizing predominance was apparent.

Conclusions: The ictal bradycardia syndrome should be considered in patients with unusual or refractory episodes of syncope, or in patients with a history suggestive of both epilepsy and syncope. It suggests seizure onset in temporal lobe, and is more commonly diagnosed in males. Diagnosis may be aided by ambulatory EEGECG monitoring. Cardiac pacemaker implantation along with antiepileptic drug therapy may be necessary to minimize the possibility of death.
Cortical Hypometabolism and Delayed Myelination in West Syndrome
Authors: Natsume Jun , Watanabe Kazuyoshi , Maeda Norihide , Kasai Keiko , Negoro Tamiko , Aso Kosaburo , Nakashima Sachie , Tadokoro Masanori
Published: August 2005

Summary: Purpose: We examined the relation between cortical hypometabolism and delayed myelination in patients with West syndrome (WS).

Methods: Serial positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) and magnetic resonance imaging (MRI) were performed in 18 patients with WS, first at the onset of epileptic spasms and later at age 10 months. The age at onset of seizures ranged from 2 to 7 months. Ten patients were diagnosed as having cryptogenic WS and 8 as having symptomatic WS.

Results: Cortical hypometabolism was detected in many patients at onset of epilepsy, but disappeared later, whereas delayed myelination tended to become evident with age. PET showed diffuse or focal cortical hypometabolism in 12 patients at onset, but in only 6 patients at age 10 months. MRI showed delayed myelination in only 2 patients at onset of epilepsy, but the number of patients with delayed myelination increased to 12 at age 10 months. Delayed myelination was more often present in patients with cortical hypometabolism. Delayed myelination was noted in 11 (85%) of 13 patients with cortical hypometabolism on first or second PET scans, but in only 1 (20%) of 5 patients who did not show PET abnormalities. Hypometabolism on the first or second PET scan was positively correlated with delayed myelination at age 10 months.

Conclusions: In patients with WS, assessing myelination with MRI again at age 8–10 months is important even when MRI at the onset of epilepsy appears normal. Serial MRI and PET scans disclose more detailed pathophysiology of WS.
Adolescents with Active or Inactive Epilepsy or Asthma: A Comparison of Quality of Life
Authors: Austin Joan K. , Huster Gertrude A. , Dunn David W. , Risinger Michael W.
Published: August 2005

Summary: Purpose: We compared quality of life (QOL) in youth with inactive or active epilepsy with that of a similar sample of youth with asthma. We explored 19 different dimensions in three domains (psychological, social, and school) and also determined differences related to illness severity and gender.

Methods: Subjects were 228 adolescents (117 with epilepsy and 111 with asthma). Data were collected from clinic records and from the adolescents, their mothers, and their teachers through questionnaires and structured interviews. Data were analyzed by analysis of covariance.

Results: The analysis with all 19 QOL variables indicated a significant difference between the total asthma and the total epilepsy samples (multivariate F = 3.36, p = 0.0001). Further evaluation reflected differences between the epilepsy group and the asthma group on 13 of the 19 QOL variables. When active and inactive epilepsy and asthma groups were compared, youth with active epilepsy were faring worse than all other groups in 10 areas. Moreover, youth with inactive epilepsy were faring worse than those with inactive asthma in four areas. Illness severity and sex differences were more strongly related to QOL in the epilepsy sample than in the asthma sample. Sex‐severity interactions suggested that girls with high seizure severity were most at risk for QOL problems.

Conclusions: Youth with active epilepsy generally had the poorest QOL. Severe seizures and female sex were associated with more problems. Sex‐severity interactions should be explored in future research.
Abnormalities in Brain Serotonin Concentration, High‐Affinity Uptake, and Tryptophan Hydroxylase Activity in Severe‐Seizure Genetically Epilepsy‐Prone Rats
Authors: Statnick Michael A. , Dailey John W. , Jobe Philip C. , Browning Ronald A.
Published: August 2005

Summary: We characterized the nature of the deficit in brain serotonin (5‐HT) exhibited by genetically epilepsy‐prone rats (GEPR‐9s) by regionally assessing three markers for 5‐HT terminals/neurons (5‐HT content, 5‐HT uptake into the P2synaptosomal fraction, and tryptophan hydroxylase activity) in GEPR‐9s and nonepileptic control rats. As compared with controls, GEPR‐9s had reduced brain 5‐HT concentration, synaptosomal 5‐HT uptake, and tryptophan hydroxylase activity (measured in vivo and in vitro) in most regions of the forebrain and in selected regions of brainstem. Analysis of kinetic constants for synaptosomal [3H]5‐HT uptake and in vitro tryptophan hydroxylase activity showed that the decrements in these parameters exhibited by GEPR‐9s resulted from reductions in Vmax rather than changes in Km. In general, the reduction in each of the presynaptic markers for 5‐HT terminals/neurons was similar in both magnitude and in their regional distribution in the GEPR‐9 brain. An exception to this was noted in the midbrain tegmentum of GEPR‐9s, which displayed a significant reduction in tryptophan hydroxylase activity without showing alterations in 5‐HT concentration or in high‐affinity 5‐HT uptake. The present findings support the hypothesis that there is a widespread reduction in the number of serotonergic terminals/neurons in GEPR‐9 brain.
Pharmacology of Cortical Epileptic Afterdischarges in Rats
Authors: Kubová H. , Lanštiaková M. , Mocková M. , Mareš P. , Vorlíček J.
Published: August 2005

Summary:Afterdischarges (ADS) elicited by electrical stimulation of the sensorimotor cortical area are characterized by rhythmic spikes and spike‐wave complexes in the EEG and by clonic face and forelimb seizures. We studied the sensitivity of such ADS to phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), primidone (PRM), and valproate (VPA) in 78 adult male Wistar rats with implanted electrodes. Neither PHT (30 and 60 mg/kg intraperitoneally, i.p.) nor CBZ (25 and 50 mg/kg i.p.) suppressed cortical ADS. Indeed, ADS were prolonged by higher doses of both drugs. PRM had a similar effect: A dose of 40 mg/kg transiently shortened ADS, but a dose of 80 mg/kg prolonged ADS. PB (20 and 40 mg/kg) and VPA (200 and 400 mg/kg) were effective in suppressing ADS. Higher doses of VPA and PB reduced the intensity of motor phenomena related to the stimuli but had no effect on the motor correlates of ADS. These findings suggest that cortically induced ADS are not a good model of secondarily generalized seizures. The response to VPA and PB suggests that cortical ADS may represent a model of myoclonic seizures.
Clinical Indicators of Genetic Susceptibility to Epilepsy
Authors: Ottman Ruth , Lee Joseph H. , Risch Neil , Hauser W. Allen , Susser Mervyn
Published: August 2005

Summary:We evaluated clinical indicators of genetic susceptibility to epilepsy in the families of 1,957 adults with epilepsy (probands) ascertained from voluntary organizations. Very few of the probands in this series had idiopathic epilepsy syndromes. Among relatives of probands with postnatal CNS insults, risks of epilepsy were no higher than in the general population. Risk was increased in relatives of probands without identified CNS insults (i.e., those with idiopathic/cryptogenic epilepsy) or with neurological deficit presumed present at birth, compared with relatives of probands with postnatal CNS insults. Among relatives of probands with idiopathic/cryptogenic epilepsy, risks were higher in parents and siblings, but not in offspring, of probands with generalized onset as compared with partial onset seizures. Risks in offspring were higher if the probands had onset of idiopathic/cryptogenic epilepsy before age 10 as compared with age 10 years, but risks in parents and siblings were not associated with the proband's age at onset. These results suggest that genetic susceptibility increases risk of some forms of cryptogenic epilepsy and of epilepsy associated with neurological deficit presumed present at birth, but not of postnatal symptomatic epilepsy. The influences on risk in offspring may differ from those in parents and siblings.
Risk Factors of Infantile Spasms Compared with Other Seizures in Children Under 2 Years of Age
Authors: Rantala Heikki , Shields W. Donald , Christenson Peter D. , Nielsen Claus , Buch Dorte , Jacobsen Vibeke , Zachau‐Christiansen Bengt , Uhari Matti , Cherry James D.
Published: August 2005

Summary: To analyze the magnitude of the risk factors for infantile spasms, we evaluated the records of 80 children with infantile spasms, 474 children with other types of epilepsy, 2,196 children with febrile seizures, and 262 children with CNS infections. There was a family history of seizures in 13.8% of children with infantile spasms, 28.5% of children with other forms of epilepsy, 25.5% of children with febrile seizures, and 5.3% of children with CNS infections. Children with a family history of seizures were 2.82 times more likely to have infantile spasms, 7.05 times more likely to have other epilepsy, and 6.08 times more likely to have febrile seizures than controls (children with CNS infections). However, a family history of seizures increased the risk for infantile spasms only in the cryptogenic group. Children with infantile spasms were significantly more likely to have cerebral palsy, microcephaly, hydrocephaly, CNS malformations, neonatal hypoxia, or neonatal seizures than children with other types of epilepsy, febrile seizures, or CNS infections. There was a modest genetic predisposition to seizures in children with infantile spasms. However, our data suggest a much stronger association with underlying neurologic abnormalities, mainly neonatal seizures, neonatal hypoxia, and CNS malformations.
Long‐Term Outcome of West Syndrome: A Study of Adults with a History of Infantile Spasms
Authors: Riikonen R.
Published: August 2005

Summary: To our knowledge, ours is the first study to evaluate the outcome of infantile spasms (IS) in adult patients. We analyzed 214 children born between 1960 and 1976 who had been followed for 20–35 years or until death at 3 months to 30 years of age. Mortality was 31% (67 of 214 patients). Thirty‐six of the surviving patients (24%) had normal (25 patients) or only slightly impaired (11 patients) intelligence as assessed by their educational abilities. Four had academic occupations. Eight were married or living unmarried with a partner. Five had healthy children. At follow‐up, the EEGs of the 25 normal persons were either normal or slightly abnormal, demonstrated focal findings in 9 (36%), and had unspecific changes in 1. Focal abnormalities were not more common in patients with less good outcomes (37%). In patients with normal neurological outcomes, IS had been classified as cryptogenic only in 9 of 25 (36%) cases. Therefore, some patients with IS apparently have normal intelligence and socioeconomic status as adults, including patients whose spasms were either symptomatic or associated with focal EEG findings.
Postictal Pulmonary Edema Requires Pulmonary Vascular Pressure Increases
Authors: Johnston S. Claiborne , Darragh Teresa M. , Simon Roger P.
Published: August 2005

Summary: The pathogenesis of neurogenic pulmonary edema has been debated for many years. Whether cardiogenic mechanisms and increased pulmonary vascular pressures are primary or even necessary for the production of pulmonary edema has been argued. We used postictal pulmonary edema to study this problem in a sheep model of neurogenic pulmonary edema with bicucullin‐induced status epilepticus. Seizure‐induced increases in pulmonary vascular pressures were averted with a reservoir system to maintain left atrial pressure (LAP) and pulmonary artery pressure (PAP) at preseizure levels. No increase in lung lymph flow occurred during seizures, in contrast to the doubling of lung lymph flow that occurred during seizures when ictal pulmonary vascular hypertension was not blocked. These data support a primary role of pulmonary vascular pressure increases in the production of neurogenic pulmonary edema.
Implications of Seizure Termination Location in Temporal Lobe Epilepsy
Authors: Spencer Susan S. , Spencer Dennis D.
Published: August 2005

Summary: Where propagating symptomatic seizures terminate has not been studied, but might provide insight into mechanisms of seizure termination as well as localization of epileptogenic tissue. We investigated location of seizure termination in 50 refractory temporal lobe epilepsy (TLE) patients who had intracranial EEG recording of spontaneous seizures and subsequent temporal lobe resection with > 1–year follow‐up. Only seizures that had onset in the resected temporal lobe were included. Location of the electrical termination for each seizure in each patient was categorized as diffuse, localized to the onset location, or localized elsewhere. The proportion of all seizures in each patient in each category was analyzed with respect to the outcome of surgery. Outcome was classified as seizure‐free or persistent seizures. Diffuse seizure termination was noted equally frequently in both outcome groups. However, the 27 patients without seizures postoperatively had a significantly greater proportion of seizures with termination in the onset location (67%) than did the 23 patients with persistent seizures (36%, p < 0.01). The seizure‐free patients also had a significantly lower proportion of seizures with localized termination elsewhere than the onset site (13%) than did patients with persistent seizures (45%, p < 0.005). Localization of the site of termination of seizures of focal origin to cortical regions other than the onset is associated with a poorer surgical prognosis. This observation raises the possibility of additional abnormal epileptogenic cortical regions with impaired seizure‐terminating capabilities.
Will a Critical Level of Hyperventilation‐Induced Hypocapnia Always Induce an Absence Seizure?
Authors: Wirrell Elaine C. , Camfield Peter R. , Gordon Kevin E. , Camfield Carol S. , Dooley Joseph M. , Hanna Brian D.
Published: August 2005

We wished to determine if the degree of hypocapnia correlates with increased frequency of absence seizures and if there is a critical pCO2 at which absence seizures are reliably provoked. Twelve untreated children with newly diagnosed absence epilepsy were continuously monitored by EEG and end‐expiratory CO2 recording during quiet respiration and hyperventilation (to absence seizure or exhaustion) while breathing four gas mixtures: (a) room air, (b) 100% O2, (c) 4% CO2 in room air, or (d) 4% CO2+ 96% O2. In quiet respiration, a reduction in number of spike and wave bursts and total seconds of spike and wave was noted in children breathing supplemental CO2 (gases c and d vs. gases a and b), p < 0.05. Supplemental O2 had no effect. Eight subjects had absence seizures elicited with each trial of hyperventilation. All subjects had their own critical pCO2, ranging from 19 to 28 mmHg. Three children had no seizures, two despite hypocapnia to pCO2 of 19 and 21 and 1 who achieved a pCO2 of only 25. In 1, absence seizures were provoked in only six of nine hyperventilation trials to pCO2 of 17–23. In 67% of subjects, absence seizures were reliably provoked by hypocapnia. Critical pCO2 varied among children with absence. Determination of whether variation in sensitivity to hypocapnia may be helpful in determining response to antiepileptic drugs (AEDs) or remission of seizures will require further study.
Cognitive Effects of Resecting Basal Temporal Language Areas
Authors: Krauss G. L. , Fisher R. , Plate C. , Hart J. , Uematsu S. , Gordon B. , Lesser R. P.
Published: August 2005

Summary: Electrical stimulation of the basal temporal region of the dominant hemisphere before partial temporal lobectomy for epilepsy sometimes produces temporary interruption of language function, but the significance of removal of this area is unknown. We evaluated the correlation between resection of the basal temporal language areas (BTLA) and certain types of postoperative language deficits. In a population of 25 patients, we mapped the inferolateral temporal lobe with cortical electrical stimulation, verifying the positions of the stimulating electrodes with three‐dimensional computed tomography (CT). Eighty percent of the patients developed transient language deficits with stimulation, particularly with tests of confrontation naming and comprehension. BTLA was primarily located in the fusiform gyrus, from 1 to 9 cm from the temporal tip. At testing 6–12 months after operation, patients with BTLA resection performed worse (mean 9% decrease) than those with no BTLA resection (mean 4% improvement) on tests of confrontation naming (p = 0.03). Resection size accounted for less of the variance in decrease in confrontation naming than did resection of the BTLA. Tests of performance I.Q. (PIQ), verbal I.Q. (VIQ), or recognition memory for word and verbal learning showed no significant difference between these groups. Most patients do not have language decrease with removal of basal temporal lobe 5–6 cm from the tip, even with removal of BTLA. Some patients, however, have persistent decrease in naming.
Effect of Valproate on Cerebral Metabolism and Blood Flow: An18F‐2‐Deoxyglusose and15O Water Positron Emission Tomography Study
Authors: Gaillard William D. , Zeffiro Thomas , Fazilat Shahin , DeCarli Charles , Theodore William H.
Published: August 2005

Summary:We compared the effect of valproate (VPA) on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF), measured with18F‐2–deoxyglucose (I8FDG) and15O water positron emission tomography (PET), in 10 normal volunteers. Mean VPA dose was 17.7 mg/kg, and mean VPA level was 82.1 mg/L (±16.5) for 4 weeks. VPA reduced global CMRGlc by 9.4% (9.60 2 0.76 vs. 8.59 ± 1.02 mg Glc/min/100 g, p < 0.05) and regionally in all anatomic areas (p < 0.05 for 11 of 26 areas). VPA diminished global CBF by 14.9% (56.55 ± 6.70 vs. 47.48 ± 4.42 ml/min/100 g, p < 0.002) and regionally in all anatomic areas (p < 0.05 for 12 of 26 areas). No significant correlation was noted between VPA level and either global CMRGlc or CBF. The effect of VPA on global CMRGlc is similar to that of carbamazepine (CBZ) and phenytoin but less than that of phenobarbital, Valium, or combination therapy with VPA and CBZ. VPA reduced regional CBF (rCBF) but not CMRGlc in the thalamus, an effect that may be associated with VPA's mechanism of action against generalized seizures.
Postictal Psychosis: A Comparison with Acute Interictal and Chronic Psychoses
Authors: Kanemoto Kousuke , Kawasaki Jun , Kawai Itsuo
Published: August 2005

Summary: We studied 30 patients with postictal psychosis and compared them with 33 patients with acute interictal psychosis and 25 patients with chronic psychosis. All patients had either complex partial seizures (CPS) or EEG temporal epileptogenic foci. Patients with postictal psychosis had a high incidence of psychic auras and nocturnal secondarily generalized seizures. The most striking feature that distinguished postictal psychosis from both acute interictal and chronic psychoses was phenomenological: the relatively frequent occurrence of grandiose delusions as well as religious delusions in the setting of markedly elevated moods and feeling of mystic fusion of the body with the universe. In addition, postictal psychosis exhibited few schizophreniform psychotic traits such as perceptual delusions or voices commenting. Reminiscence, mental diplopia, and a feeling of impending death were also fairly frequent complaints of patients with postictal psychosis. Interictal acute psychosis and chronic epileptic psychosis were psychopathologically similar. Although acute interictal and chronic epileptic psychoses could simulate schizophrenia, postictal psychosis results in a mental state quite different from that of schizophrenic psychosis.
A Brief Questionnaire to Screen for Quality of Life in Epilepsy The QOLIE‐10
Authors: Cramer Joyce A. , Perrine Kenneth , Devinsky Orrin , Meador Kimford
Published: August 2005

Summary: Purpose: To evaluate a brief questionnaire to screen aspects of health‐related quality of life for persons with epilepsy.

Methods: A study of 304 adults with epilepsy was undertaken at 25 seizure clinics in the United States. It was used for derivation of a brief screening tool from a longer instrument (QOLIE‐89).

Results: The 10–item questionnaire (QOLIE‐10) covers general and epilepsy‐specific domains, grouped into three factors: Epilepsy Effects (memory, physical effects, and mental effects of medication), Mental Health (energy, depression, overall quality of life), and Role Functioning (seizure worry, work, driving, social limits). Scale scores were significantly different among seizure groups (p = 0.003).

Conclusions: The QOLIE‐10 can be completed by a patient in several minutes and reviewed rapidly by the physician. This screening tool could provide potentially useful information for initial assessment or follow‐up of problem areas that are not commonly evaluated during routine clinical visits with patients with epilepsy.
Magnetic Resonance Spectroscopy
Authors: Duncan John S.
Published: August 2005

Magnetic resonance spectroscopy (MRS) is noninvasive and may be readily combined with magnetic resonance imaging (MRI). Attention has focussed on proton (1H) and phosphorus (31P) MRS, and studies have been undertaken by using single voxels or many voxels simultaneously (chemical‐shift imaging, magnetic resonance spectroscopic imaging). The latter is more difficult and prone to artefact but potentially yields significantly more information. 1H MRS has principally yielded data on concentrations of N‐acetyl aspartate (NAA), choline, creatine, and phosphocreatine. NAA is located primarily within neurons, and reduction of the ratio of NAA to choline, creatine, and phosphocreatine is a marker of neu‐ronal loss and dysfunction. This technique may be useful as a noninvasive tool for localizing epileptogenic foci, but its role requires further evaluation. As with all functional imaging methods, coregistration with high‐quality MRI is essential for interpreting data. 1H MRS can be used also to estimate cerebral concentrations of several neurotrans‐mitters: glutamate, glutamine, and γ‐aminobutyric acid (GABA). This may prove useful for characterizing the neurometabolic profiles of patients with different epilepsy syndromes and for evaluating the effects of medical and surgical treatments. 31P MRS can detect adenosine tri‐phosphate, phosphodiesters, phosphomonoesters, phosphocreatine, and inorganic phosphate, and estimate intra‐cerebral pH. Abnormalities that have been associated with epileptogenic brain areas include increased inorganic phosphate, reduced phosphomonoesters, and increased pH. Only small numbers of patients have been studied, however, so that conclusions are not definitive, and the clinical role of this technique is not yet established.
Coupling of Cortical and Thalamic Ictal Activity in Human Partial Epilepsy: Demonstration by Functional Magnetic Resonance Imaging
Authors: Detre John A. , Alsop David C. , Aguirre Geoffrey K. , Sperling Michael R.
Published: August 2005

Summary: Purpose: To localize metabolic coupling between a cortical seizure focus and other brain regions by using functional magnetic resonance imaging (fMRI) data of ictal events obtained in a patient with frequent partial seizures involving his right face.

Methods: Cross‐correlation analysis was used to examine time‐dependent alterations in regional signal intensity that correlated with signal‐intensity changes from a well‐characterized cortical seizure focus in a patient with frequent partial seizures.

Results: Signal changes in the left ventrolateral thalamus showed a high degree of temporal correlation with signal changes in the left frontal cortical seizure focus, demonstrating close corticothalamic coupling of metabolism.

Conclusions: A significant role for thalamocortical interactions in the pathophysiology of epilepsy has been suggested by studies in animal models and human patients. This finding provides further support for the integral involvement of the thalamus in human focal epilepsy and underscores the potential for identifying neuronal networks by using cross‐correlation analysis of fMRI data.
Subdural Recording of Ictal DC Shifts in Neocortical Seizures in Humans
Authors: Ikeda Akio , Terada Kiyohito , Mikuni Nobuhiro , Burgess Richard C. , Comair Youssef , Taki Waro , Hamano Toshiaki , Kimura Jun , O.Lüders Hans , Shibasaki Hiroshi
Published: August 2005

Summary: Purpose: Invasive ictal EEG recording is often necessary to delineate epileptogenic areas in patients with intractable partial epilepsy, but even intracranial ictal recordings often reveal ill‐defined onset zones in neocortical epilepsy. We studied the physiologic significance of ictal direct current (DC) potentials recorded intracranially in human epilepsy.

Methods: We made intracranial ictal EEG recordings in three patients with intractable partial seizures arising from frontal, lateral temporal, and parietal neocortical areas by using closely spaced subdural electrodes (platinum in two patients and stainless steel in one patient) with both standard (1.5 Hz) and open (0.016 Hz) low‐frequency filter (LFF) settings.

Results: The initial ictal pattern was localized to two to nine subdural electrodes and characterized by very low voltage and high‐frequency rhythmic activity (“electrode‐cremental pattern”). A slow‐rising negative potential (DC potential) was seen in a slightly more restricted area (two to six electrodes) and occurred 1–10 s before the initial ictal EEG discharges in two patients.

Conclusions: These results agree with those of previous studies of ictal DC shifts in animals and suggest that ictal DC shifts may be helpful in delineating the epileptogenic area more precisely in human epilepsy.
Effect of L‐Carnitine Supplementation on Acute Valproate Intoxication
Authors: Murakami K. , Sugimoto T. , Woo M. , Nishida N. , Muro H.
Published: August 2005

Summary: We analyzed urinary valproate (VPA) metabolites and carnitine concentrations in a child who accidentally ingested 400 mg/kg VPA. The concentration of 4‐en VPA, the presumed major factor in VPA‐induced hepato‐toxicity, was markedly increased, without liver dysfunction or hyperammonemia. The other major abnormality was decreased β‐oxidation and markedly increased ω‐oxidation. After L‐carnitine supplementation, VPA metabolism returned to normal. The level of valproylcarnitine was not increased and therefore was not affected by L‐carnitine. L‐Carnitine may be useful in treating patients with coma after VPA overdose.