bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Myoclonic Epilepsy of Infancy: Extended Spectrum of GEFS+?
Authors: Singh R. , Andermann E. , Whitehouse W. P. A. , Harvey A. S. , Keene D. L. , Seni M‐H. , Crossland K. M. , Andermann F. , Berkovic S. F. , Scheffer I. E.
Published: March 2003

Summary:  Purpose: Severe myoclonic epilepsy of infancy (SMEI) is an intractable epilepsy of early childhood of unknown etiology. It is often associated with a family history of seizure disorders, but epilepsy phenotypes have not been well described. We sought to characterize the seizure phenotypes of relatives to better understand to the genetic basis of SMEI.

Methods: Probands with SMEI were identified, and systematic family studies were performed. Epilepsy syndromes were characterized in affected family members.

Results: Twelve probands with SMEI were identified. Eleven of the 12 probands with SMEI had a family history of seizures, and the twelfth was the result of a consanguineous marriage. We found that 16.7% of full siblings and 8.3% of parents had definite seizures. A total of 39 affected family members was identified. The most common phenotype was febrile seizures in 14, febrile seizures plus in seven, partial epilepsy in two, and there were single individuals with SMEI, myoclonic–astatic epilepsy, Lennox–Gastaut syndrome, and 13 cases with unclassified or unconfirmed seizures.

Conclusions: The family history of seizures in SMEI is in keeping with the spectrum of seizure phenotypes seen in generalized epilepsy with febrile seizures plus (GEFS+). Our findings suggest that SMEI is the most severe phenotype in the GEFS+ spectrum.
Neuroimaging Findings of Cortical Dyslamination with Cytomegaly
Authors: Lee Sung Kun , Choe Gheeyoung , Hong Keun‐Sik , Nam Hyun‐Woo , Kim Joo‐Yong , Chung Chun‐Kee , Lee Dong‐Soo , Chang Kee‐Hyun
Published: March 2003

Summary:  Purpose: Our aims were to identify (a) the characteristic magnetic resonance imaging (MRI) findings of cortical dyslamination with cytomegaly, including dysplastic and destructive lesions; (b) the relationship between MRI findings and pathologic characteristics; (c) the diagnostic role of functional neuroimaging studies in patients with these pathologies.

Methods: The series consisted of 23 adult patients who had proven cortical dyslamination with cytomegaly. The abnormalities found on MRI were subdivided according to the patterns of involvement. They also were compared with the patients' pathologic characteristics. With visual qualitative analysis, [18F]fluorodeoxyglucose with positron emission tomography (FDG‐PET), and ictal single‐photon emission computed tomography (SPECT), observations were classified as localizing, lateralizing, nonlateralizing, false‐localizing, and false‐lateralizing. The standard for correct localization of neuroimages was defined to be the resected lobe.

Results: Focal abnormalities were found in 14 cases by MRI. Six cases showed typical MRI findings of focal cortical dysplasia, with focal areas of cortical thickening with or without poor grey–white matter differentiation. Focal subcortical high signal intensities on T2‐weighted images occurred in two cases. Six patients had the focal destructive pattern. Three of eight cases with normal MRI and four of eight cases with the nondestructive cortical dysplasia pattern had balloon cells. However, these were not found in six patients with the destructive MRI pattern. FDG‐PET localized the pathologic lobe in 13 (65%) of 20 cases, and ictal SPECT achieved this in 11 (61.1%) of 18 cases. FDG‐PET and ictal SPECT also correctly localized the pathologic lobe in four and two cases with normal MRI, respectively.

Conclusions: Two distinct patterns of abnormal MRI were found in the pathology of cortical dyslamination with cytomegaly. These dysplastic and destructive patterns might reflect different pathogeneses, such as the time of insult. FDG‐PET and ictal SPECT have confirmatory and independent diagnostic roles in localizing epileptogenic foci.
A Case of Ohtahara Syndrome with Olivary–dentate Dysplasia and Agenesis of Mamillary Bodies
Authors: Trinka E. , Rauscher C. , Nagler M. , Moroder T. , Ladurner G. , Irnberger E. , Sperl W. , Pilz P.
Published: March 2003

Summary: We report a patient with early infantile epileptic encephalopathy (EIEE) with suppression‐burst (Ohtahara syndrome) associated with olivary–dentate dysplasia and agenesis of mamillary bodies is reported. Although those with Ohtahara syndrome are a heterogeneous group, virtually all reported cases are secondary to neuronal migrational disorders, sometimes only identified by detailed neuropathologic examination, as in this case report, which describes mamillary body agenesis as a not‐yet‐recognized anomaly associated with Ohtahara syndrome. All children with Ohtahara syndrome should have high‐resolution magnetic resonance imaging (MRI) and detailed postmortem neuropathologic examinations.
Comparison of Hippocampal Volumetry at 1.5 Tesla and at 3 Tesla
Authors: Briellmann Regula S. , Syngeniotis Ari , Jackson Graeme D.
Published: March 2003

Summary:  Purpose: Hippocampal volumetry using magnetic resonance imaging (MRI) is a common clinical study in epilepsy patients. Most clinical MR scans operate at 1.5 tesla (T); however, there is increasing use of scanners of a higher field strength. We analyzed whether control data of hippocampal volumes can be used across different field‐strength scanners.

Methods: We studied eight adult healthy controls twice at both 1.5 and 3 T. Bilateral hippocampal volumes were measured by manual outlining. Measurement error was analyzed based on the variability between two measurements at the same field strength, and intrascanner variability was analyzed based on the difference between measurements obtained at 1.5 and at 3 T.

Results: The measurement error was 4.0% (±3.1) at 1.5 T, and 3.4% (±2.5) at 3 T. The intrascanner variability between measurements at 1.5 and at 3 T was 6% (±3.9). The intrascanner variability was not different from the measurement error.

Conclusions: Control hippocampal volume measurements obtained at 1.5 and at 3 T were not different.
Neurosteroid Withdrawal Model of Perimenstrual Catamenial Epilepsy
Authors: Reddy Doodipala S. , Kim Hee‐Yong , Rogawski Michael A.
Published: March 2003

Summary:  Purpose: Perimenstrual catamenial epilepsy, the increase in seizure frequency that some women with epilepsy experience near the time of menstruation, may in part be related to withdrawal of the progesterone metabolite allopregnanolone, an endogenous anticonvulsant neurosteroid that is a potent positive allosteric γ‐aminobutyric acidA (GABAA) receptor modulator. The objective of this study was to develop an animal model of perimenstrual catamenial epilepsy for use in evaluating drug‐treatment strategies.

Methods: A state of prolonged high serum progesterone (pseudopregnancy) was induced in 26‐day‐old female rats by sequential injection of pregnant mares' serum gonadotropin and human chorionic gonadotropin. Neurosteroid withdrawal was induced by treatment with finasteride (100 mg/kg, i.p.), a 5α‐reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Plasma progesterone and allopregnanolone levels were measured by gas chromatography/electron capture negative chemical ionization mass spectrometry. Seizure susceptibility was evaluated with the convulsant pentylenetetrazol (PTZ).

Results: Plasma allopregnanolone levels were markedly increased during pseudopregnancy (peak level, 55.1 vs. control diestrous level, 9.3 ng/mL) and were reduced by 86% 24 h after finasteride treatment (6.4 ng/mL). Progesterone levels were unaffected by finasteride. After finasteride‐induced withdrawal, rats showed increased susceptibility to PTZ seizures. There was a significant increase in the number of animals exhibiting clonic seizures when challenged with subcutaneous PTZ (60 mg/kg) compared with control pseudopregnant animals not undergoing withdrawal and nonpseudopregnant diestrous females. The CD50 (50% convulsant dose) was 46 mg/kg, compared with 73 mg/kg in nonwithdrawn pseudopregnant animals and 60 mg/kg in diestrous controls. The threshold doses for induction of various seizure signs, measured by constant intravenous infusion of PTZ, were reduced by 30–35% in neurosteroid‐withdrawing animals compared with control diestrous females. No change in threshold was observed in pseudopregnant rats treated from days 7 to 11 with finasteride, demonstrating that high levels of progesterone alone do not alter seizure reactivity.

Conclusions: Neurosteroid withdrawal in pseudopregnant rats results in enhanced seizure susceptibility, providing an animal model of perimenstrual catamenial epilepsy that can be used for the evaluation of new therapeutic approaches.
Childhood Epilepsy Due to Neurocysticercosis: A Comparative Study
Authors: Ferreira Lisiane S. , Zanardi Verônica A. , Scotoni Anna E. , Li Li Min , Guerreiro Marilisa M.
Published: March 2003

Summary:  Purpose: To assess the clinical profile of pediatric patients with epilepsy and neurocysticercosis (NC), and compare them with a group of pediatric patients with benign partial epilepsy to determine clinical differences, response to treatment, and prognosis.

Methods: We studied 28 patients (16 girls) with probable or definitive diagnosis of NC and epilepsy and 32 patients (16 girls) with partial benign epilepsy (BE). All patients had normal neurologic examination. We compared NC and BE patients looking for differences in demographics (age at first seizure, gender, family history); clinical presentation (type, frequency, duration, and total number of seizures, duration of epilepsy, status epilepticus, cluster, and postictal deficit); treatment [duration, number of antiepileptic drugs (AEDs), maximal dose, drug association, number of seizure‐free patients, time to obtain control and recurrence after medication discontinuation]; complementary examinations (the first and the last EEG).

Results: The mean follow‐up was 5.4 years for the 28 NC patients and 4.6 years for the 32 BE patients (p = 0.98). We did not find statistical differences between NC and BE in gender, family history, types of seizures, frequency and length of seizures, previous status epilepticus, seizure clustering, and presence of postictal deficits. However, we found that NC compared with BE patients had significant longer AED treatment, more seizures after AED introduction, tried more AEDs and at maximal dose, and in 20%, required polytherapy. The recurrence rate in NC was 54.4% and this was not significantly associated with number of lesions and disease activity seen on CT scans or the presence of EEG abnormalities.

Conclusions: NC presents with a mild form of epilepsy in terms of seizure severity; however, it is more challenging in regard to drug management and has a less favorable long‐term prognosis in terms of seizure remission. The number of lesions or disease activity seen on computed tomography (CT) as well as EEG abnormalities have no prognostic value in childhood epilepsy due to NC.
Mental Retardation in Pediatric Candidates for Epilepsy Surgery: The Role of Early Seizure Onset
Authors: Vasconcellos Elza , Wyllie Elaine , Sullivan Shawn , Stanford Lisa , Bulacio Juan , Kotagal Prakash , Bingaman William
Published: March 2003

Summary:  Purpose: We sought to determine whether early age at seizure onset is a risk factor for mental retardation, independent of etiology. Assessment of risk for mental retardation with continued uncontrolled seizures plays a role in considerations of timing for epilepsy surgery. Previous studies have indicated that onset of seizures in the first years of life may be a risk factor for mental retardation, but the etiologies of the epilepsies were not included in the analyses.

Methods: Intellectual function was assessed at ages 2–20 years during presurgical evaluation in 100 patients with intractable epilepsy due to focal lesions limited to part of one lobe of the brain. Mental retardation (MR) was defined as Full‐Scale Intelligence Quotient (FSIQ) ≤70. The age at seizure onset and the seizure frequency were obtained retrospectively.

Results: Younger ages at seizure onset were associated with lower FSIQ scores, and mean FSIQ was also significantly lower for patients with onset of epilepsy at ≤24 months of age (74.0 ± 21.5) versus that in patients with onset of epilepsy later in life (87.8 ± 18.8; p = 0.005). The frequency of patients with MR was significantly higher for patients with seizure onset at ≤24 months of age (15 of 33, 46%) than for patients with seizure onset later in life (eight of 67, 12%; p < 0.001). This difference persisted within etiologic subgroups. For patients with focal malformation of cortical development, MR was seen in eight (50%) of 16 patients with seizure onset at ≤24 months versus two (10%) of 20 patients with seizure onset at >24 months (p < 0.001); for patients with tumor, MR was seen in four (50%) of eight patients with seizure onset at ≤24 months versus four (13%) of 30 patients with seizure onset at >24 months (p = 0.003); and for patients with hippocampal sclerosis, MR was seen in two (28%) of seven patients with seizure onset at ≤24 months versus none of 30 patients with seizure onset at >24 months (NS). Within the subgroup with daily seizures, MR was present in 13 (65%) of 20 patients with seizure onset at ≤24 months versus five (17%) of 29 patients with seizure onset later in life (p = 0.001).

Conclusions: These results indicate that onset of intractable epilepsy within the first 24 months of life is a significant risk factor for MR, especially if seizures occur daily. The risk based on early age at seizure onset appeared independent of etiology and persisted within subgroups of patients with focal malformation of cortical development, tumor, or hippocampal sclerosis. Prospective studies will be important to clarify whether early surgical intervention may reduce the risk for subsequent MR in carefully selected infants.
An Incident Case–Control Study of First Unprovoked Afebrile Seizures in Children: A Population‐Based Study of Pre‐ and Perinatal Risk Factors
Authors: Sidenvall R. , Heijbel J. , Blomquist H. K. , Nyström L. , Forsgren L.
Published: March 2003

Summary:  Purpose: The aim of this prospective incident community‐based study was to assess the influence of pre‐ and perinatal risk factors in children in whom an unprovoked afebrile epileptic seizure later developed.

Methods: From November 1, 1985, until June 30, 1987, 75 children aged 0–15 years with a first unprovoked afebrile seizure were identified. After exclusion of cases with neonatal seizures (n = 14), two controls per case were selected from the same province in northern Sweden matched by age and sex. Files from maternity wards and pediatric clinics could be traced for 58 cases and 109 controls. These formed the study group.

Results: In the univariate analysis, the risk for an unprovoked afebrile seizure was significantly elevated for birth order (OR = 9.3; CI, 2.2–39), vaginal bleeding (OR = 17; 95% CI, 3.5–85), onset of hypertension during pregnancy (OR = 4.8; CI, 1.3–17), cesarean section (OR = 18; 95% CI, 3.7–88), short or long gestational age (OR = 6.7; 95% CI, 2.0–22), and an Apgar score ≤6 at any time (OR = 3.8; 95% CI, 1.2–12). None of these six factors was present in 48.3% of the cases and 89% in the controls. A combination of two or more risk factors found to be significant in the univariate analysis showed a pronounced increased risk for seizures (OR = 19; 95% CI, 5.6–65). In the multivariate analysis, the following characteristics remained statistically significant: vaginal bleeding, gestational age, and Cesarean section. Furthermore, smoking also was identified as a risk factor in the multivariate analysis (OR = 3.4; 95% CI, 1.1–10).

Conclusions: Both pre‐ and perinatal factors may be associated with later development of epileptic seizures in children. However, in many of the cases, no such factors were identified.
Memory Outcome after Left Anterior Temporal Lobectomy in Patients with Expected and Reversed Wada Memory Asymmetry Scores
Authors: Sabsevitz David S. , Swanson Sara J. , Morris George L. , Mueller Wade M. , Seidenberg Michael
Published: March 2003

Summary:  Purpose: The ideal candidate for anterior temporal lobectomy surgery shows a Wada memory asymmetry (WMA) score characterized by better memory performance in the hemisphere contralateral to the seizure focus relative to the ipsilateral (surgical) hemisphere. However, some surgical candidates show a reversed WMA or better Wada memory performance in the hemisphere of surgical interest relative to the hemisphere contralateral to the seizure focus. To date, no data are available contrasting memory and seizure outcome for these two Wada groups. The present study compared memory and seizure outcome after left anterior temporal lobectomy (L‐ATL) in patients showing expected and reversed WMA scores, and also examined the relationship of the individual hemisphere Wada memory scores for predicting verbal memory outcome after L‐ATL.

Methods: We compared 6‐month postoperative verbal memory change scores and seizure outcome in L‐ATL patients with either an expected (n = 12) or reversed WMA (n = 9) pattern on Wada memory testing.

Results: L‐ATL patients showing a reversed WMA score had a poorer verbal memory outcome and poorer seizure control after surgery compared with patients showing a WMA score in the expected direction.

Conclusions: L‐ATL patients with a reversed WMA score have a greater risk for memory morbidity and poorer seizure outcome than do patients with a WMA score in the expected direction. The WMA score was the best predictor of memory outcome after L‐ATL. When the WMA score is not considered, both individual Wada hemisphere scores (contralateral and ipsilateral) provided significant and independent contribution to predicting postoperative verbal memory functioning. These findings are discussed in the context of the functional reserve and hippocampal adequacy models of memory change after temporal lobectomy.
Postmarketing Experience with Topiramate and Cognition
Authors: Tatum W. O. , French J. A. , Faught E. , Morris G. L. , Liporace J. , Kanner A. , Goff S. L. , Winters L. , Fix A. ,   the PADS Investigators
Published: March 2003

Summary: Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS‐related treatment‐emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double‐blind, placebo‐controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post‐marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open‐label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment.  We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with “better” or “much better” ratings of both seizure and global improvement during treatment.
Lateralized Postictal EEG Delta Predicts the Side of Seizure Surgery in Temporal Lobe Epilepsy
Authors: Jan Mohammed M. S. , Sadler Mark , Rahey Susan R.
Published: March 2003

Summary:  Purpose: The concordance of lateralized EEG postictal polymorphic delta activity (PPDA) to the side of seizure origin in temporal lobe epilepsy (TLE) has received limited study. Our objective was to study the lateralizing value of PPDA in patients with documented TLE.

Methods: A cohort of consecutive adults with TLE, detailed presurgical evaluation before temporal lobectomy, and minimal follow‐up of 2 years were included. One author masked the ictal rhythm of presurgical EEGs and randomly presented 20 s of preictal and the postictal EEG to two electroencephalographers who were blind to all clinical data. They independently assigned PPDA to one of three categories: not present, bilateral, or lateralized (defined as newly appearing or an amplitude >50% of the preictal record).

Results: Eighty seizures from 29 patients were studied. Fifteen patients had a left, and 14 had a right temporal lobectomy. Twenty‐three patients were seizure free or substantially improved (defined as simple partial or nocturnal seizures only). Lateralized PPDA was present in 64% of all EEGs and at least one record from 22 (76%) patients. Lateralized PPDA, when present, was concordant with the side of surgery in 96% of the EEGs.

Conclusions: Lateralized PPDA is highly predictive of the side of ultimate temporal lobectomy, and by inference the side of seizure origin.
Patients Treated with Vigabatrin Exhibit Central Visual Function Loss
Authors: Hilton Emma J. Roff , Cubbidge Robert P. , Hosking Sarah L. , Betts Tim , Comaish Ian F.
Published: March 2003

Summary:  Purpose: To investigate visual function in the central 10 degrees in patients who have undergone vigabatrin (VGB) antiepileptic drug (AED) therapy with the aim of identifying a clinical regimen for assessing central visual function.

Methods: The sample comprised 12 epilepsy patients (mean age, 38.6 ± 11.7 years) who had been treated with VGB (either as monotherapy or polytherapy). A number of central visual‐function tests were carried out for each eye, including high‐contrast LogMAR visual acuity, short‐wavelength automated perimetry (SWAP 10‐2), spatial contrast sensitivity (CSV‐1000), and Farnsworth‐Munsell (FM) 100‐hue colour discrimination.

Results: The group mean cumulative VGB dose was 5,086 ± 3,245 g. The average SWAP 10‐2 mean deviation (MD) for the group was –3.24 ± 3.23 dB; 14 eyes of eight patients showed defects (range, –1.62 to –9.46 dB). The square root of the group mean total error score for FM 100‐hue was 7.42 ± 3.84; nine eyes of five patients were classified as abnormal with an unsolved colour axis suggestive of complex drug interactions. For contrast sensitivity, 15 eyes of eight patients yielded abnormal results in one or more spatial frequencies. Defects were more prominent at higher spatial frequencies. Overall, four patients had defects in all three visual‐function tests, six patients had mixed defects, and two patients were normal.

Conclusions: Visual‐function deficits in epilepsy patients treated with VGB are present in the central 10 degrees of the retina. We recommend a battery of investigations, including SWAP 10‐2 and spatial contrast sensitivity testing, to assess central visual function.
Basic Mechanisms of Psychotropic Drugs
Authors: Ebert Ulrich
Published: March 2003

Summary: Many epilepsy patients, particularly those with complex partial seizures, also develop psychiatric disorders during the course of their illness and have to be treated with psychotropic drugs in addition to their antiepileptic medication. However, the brains of epileptic patients can be considered pathologically altered and psychotropic drugs may thus have profound and stronger effects on seizure threshold or unwanted side effects than in purely psychiatric patients. Thus, the knowledge of the mechanisms of psychotropic drugs is necessary to predict their effects in epilepsy patients. In this review, current concepts of the mechanisms of neuroleptic, antidepressant, and anxiolytic drugs emerging from basic and preclinical research are summarized, and the potential impact of using these drugs in epilepsy patients is discussed.
Atypical Antipsychotics and Serotoninergic Antidepressants in Patients with Epilepsy: Pharmacodynamic Considerations
Authors: Torta Riccardo , Monaco Francesco
Published: March 2003

Summary:  Purpose: To discuss the pharmacodynamic aspects of the administration of atypical antipsychotics (APs) and serotoninergic antidepressants (SSRIs) to patients with epilepsy.

Methods: This article represents an overview of all studies concerning the administration of APs and SSRIs to people with epilepsy. In particular, it deals with the relationship between neuroleptics (NLTs), APs, SSRIs, serotonin, and dopamine, with special focus on the possible epileptogenic role of psychoactive drugs.

Results: NLTs may induce seizures by blocking D2, H1, and .1 receptors, or by sexual hormone activation or a pharmacologic kindling mechanism. The difference among APs in their ability to induce seizures is related mainly to the percentage of D2‐receptor occupancy and possibly also to their action on neurosteroids. Seizures occur at SSRIs therapeutic doses, with a 0.1–4% incidence. Coversely, in animal studies fluoxetine was claimed to exert an anticonvulsant action.

Conclusions: The study of the pharmacodynamic aspects of the administration of APs and SSRIs to patients with epilepsy can help to evaluate the importance of some mechanisms of action of several psychoactive drugs in relation to their pro‐ or anticonvulsant activity.
When is it Inappropriate to Prescribe Psychotropic Medication?
Authors: Besag Frank M. C.
Published: March 2003

Summary: Psychotropic medication can be of great value in the treatment of people with epilepsy, but there are situations in which it is not appropriate and other strategies are needed. A number of different strategies, usually not involving psychotropic medication, are required for the behavioural disturbance associated with prodromal mood changes, anxiety‐provoking auras, focal discharges, frequent absence seizures, adverse reactions to antiepileptic medication or adverse reactions to antiepileptic drug interactions, difficulties arising from uneven cognitive profiles, reactions to the epilepsy, and causes that are not related to the epilepsy. The first step should always be to determine the cause or causes of behavioural disturbance. A systematic approach to the assessment of the behavioural or psychiatric problems, using a structured diagnostic framework of possible causes, provides the basis for correct diagnosis and management. This systematic approach assists the clinician in deciding when other strategies are preferable to the prescription of psychotropic medication.
Effect of Electrical Stimulation of the Nucleus of the Solitary Tract on the Development of Electrical Amygdaloid Kindling in the Cat
Authors: Magdaleno‐Madrigal Victor M. , Valdés‐Cruz Alejandro , Martínez‐Vargas David , Martínez Adrián , Almazán Salvador , Fernández‐Mas Rodrigo , Fernández‐Guardiola Augusto
Published: March 2003

Summary:  Purpose: This work analyzed the effect of electrical stimulation of the nucleus of the solitary tract (NTS) on the development of electrical amygdaloid kindling (AK) in freely moving cats.

Methods: Nine male adult cats with implanted electrodes in both amygdalae (basolateral nucleus), both lateral geniculate bodies, left NTS, and both prefrontal cortices were used. Electromyogram and electrooculogram also were recorded. The AK was performed every 24 h (1‐s train, 1‐ms pulses, 60 Hz, 300–600 μA). The NTS was stimulated previously for 1 min (0.5‐ms pulses, 30 Hz, 150–300 μA), just before the AK at 10:00 a.m., and then every 60 min, 4 times, from 11:00 a.m. to 2:00 p.m. On different days, all NTS stimulation was suspended, and AK was continued until stage VI kindling was reached.

Results: Behavioral changes produced by the stimulation of the NTS were blinking, immobility periods with upward sight, licking, and swallowing. Animals with simultaneous stimulation of NTS and AK did not reach stage VI, remaining in behavioral stages I–III. Stage VI was reached after NTS stimulation was intentionally suspended. The amplitude, duration, and the propagation of the amygdaloid afterdischarge did not exhibit progressive evolution during NTS stimulation. A regression analysis was performed between the number of days with only AK stimulation and days with simultaneous NTS stimulation, which showed a positive correlation (values of r = 0.84).

Conclusions: Our results suggest that NTS stimulation interferes with the development of convulsive evolution and secondary generalization. This delay effect may be due to the activation of the locus ceruleus and some areas of the midbrain reticular formation, among other structures, which has been demonstrated to inhibit experimental convulsive seizures.
Topiramate Kinetics during Delivery, Lactation, and in the Neonate: Preliminary Observations
Authors: Öhman Inger , Vitols Sigurd , Luef Gerhard , Söderfeldt Birgitta , Tomson Torbjörn
Published: March 2003

Summary:  Purpose: To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate.

Methods: TPM concentrations in plasma and breast milk were measured with fluorescence polarization immunoassay (FPIA) in five women with epilepsy treated with TPM during pregnancy and lactation. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions (24, 48, and 72 h) after delivery. Blood and breast milk also were collected from mothers 2 weeks, and 1 and 3 months postpartum. Blood samples also were drawn from the infants during breast‐feeding. Three of the mother–infant pairs were studied both at delivery and during lactation; two contributed with data from delivery only.

Results: The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of TPM. The mean milk/maternal plasma concentration ratio was 0.86 (range, 0.67–1.1) at 2–3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar (0.86 and 0.69, respectively). Two to 3 weeks after delivery, two of the breast‐fed infants had detectable (>0.9 μM) concentrations of TPM, although below the limit of quantification (2.8 μM), and one had an undetectable concentration.

Conclusions: Our limited data suggest free passage of TPM over the placenta and an extensive transfer into breast milk. Breast‐fed infants had very low TPM concentrations, and no adverse effects were observed in the infants.
Various Findings in Surgically Treated Epilepsy Patients with Dysembryoplastic Neuroepithelial Tumors in Comparison with Those of Patients with Other Low‐grade Brain Tumors and Other Neuronal Migration Disorders
Authors: Degen Rolf , Ebner Aloys , Lahl Rainer , Leonhardt Stephanie , Pannek Heinz W. , Tuxhorn Ingrid
Published: March 2003

Summary:  Purpose: To determine whether dysembryoplastic neuroepithelial tumors (DNTs) that belong to the neuronal migration disorders (NMDs) are to be classified with them or with “other low‐grade brain tumors” regarding several etiologic, clinical, magnetic resonance imaging (MRI), and EEG findings.

Methods: These findings of 21 DNT patients were compared with those of 13 consecutive patients with other low‐grade brain tumors and 41 NMD patients.

Results: The result is absolutely clear: nearly all findings in DNT patients (complications during pregnancy, birth, the newborn period and the postnatal period, age at first seizure, epileptic syndrome, seizure type, febrile seizures, retarded milestones, intellectual and neurologic deficits, MRI, interictal and ictal EEG findings) being similar or in agreement with those of other low‐grade brain tumors, not with those of other NMDs.

Conclusions: Regarding various clinical features including surgery outcome, MRI, and EEG findings, DNTs should be classified with the other low‐grade brain tumors, rather than with NMDs.
Interrater Reliability among Epilepsy Centers: Multicenter Study of Epilepsy Surgery
Authors: Haut Sheryl R. , Berg Anne T. , Shinnar Shlomo , Cohen Hillel W. , Bazil Carl W. , Sperling Michael R. , Langfitt John T. , Pacia Steven V. , Walczak Thaddeus S. , Spencer Susan S.
Published: March 2003

Summary:  Purpose: To measure the interrater reliability of presurgical testing and surgical decisions among epilepsy centers.

Methods: Seven centers participating in an ongoing, prospective multicenter study of resective epilepsy surgery agreed to conform to a detailed protocol regarding presurgical evaluation and surgery. To assess quality assurance, each center independently reviewed 21 randomly selected surgical cases for preoperative study lateralization and localization, and surgical decisions. Interrater reliability was assessed by using intraclass correlation coefficients (ICCs), validated for use with multiple raters, and calculated in a two‐way random model based on absolute agreement.

Results: Agreement for ICC values: ≥0.75, excellent; 0.60–0.74, good; 0.40–0.59, fair; ≤0.39, poor. One center was excluded for missing data. Agreement was excellent for extracranial EEG lateralization (0.8039), magnetic resonance imaging (MRI) lateralization (0.9521) and localization (0.9130), Wada lateralization (0.9453), and intracranial EEG localization (0.7905). Agreement was good for extracranial EEG localization (0.7384) and neuropsychological testing lateralization (0.7178) and localization (0.6891). Consensus about the decision to perform intracranial monitoring was fair (0.5397), in part reflecting one center's tendency toward intracranial monitoring. Overall agreements on whether to perform surgery (0.8311) and specific surgery recommended (0.8164) were excellent.

Conclusions: High interrater reliability among six epilepsy centers was present for interpretation of most components of presurgical testing. Although consensus for the decision to perform intracranial monitoring was only fair, agreements for the ultimate decision about resective surgery and specific choice of resection were excellent. We believe that this study demonstrates the feasibility of implementing multicenter protocols for neurologic management, especially those involving localization, as well as protocols combining study results with clinical decision making.
Psychoses and Epilepsy: Are Interictal and Postictal Psychoses Distinct Clinical Entities?
Authors: Adachi Naoto , Matsuura Masato , Hara Tsunekatsu , Oana Yasunori , Okubo Yoshiro , Kato Masaaki , Onuma Teiichi
Published: March 2003

Summary:  Purpose: To evaluate further the relevance of designating psychotic episodes as either postictal or interictal, we compared several biologic variables between epilepsy patients with and without psychosis.

Methods: The study subjects comprised 282 patients with psychosis (36 with postictal psychosis, 224 with interictal psychosis, and 22 with both postictal and interictal psychoses, i.e., bimodal psychosis), and 658 epilepsy patients without psychosis. The clinical characteristics of these patients were reviewed retrospectively by experienced neuropsychiatrists. Factors predicting the development of each type of psychosis were determined by serial multivariate logistic regression analyses.

Results: Factors that were comparable between postictal and interictal psychoses were intellectual function, family history of psychosis, epilepsy type, and the presence of complex partial seizures. In contrast, age at the onset of epilepsy and at the onset of psychosis and the presence of generalized tonic–clonic seizures differed for the three types of psychosis. Patients with bimodal psychosis showed characteristics associated with both postictal and interictal psychoses.

Conclusions: This study documented conditions, including both general factors and epilepsy‐related factors, common to epilepsy patients with psychosis, regardless of chronologic distinctions. Certain epileptic processes appear to have equal influence on postictal and interictal psychoses. However, some differences between postictal and interictal psychoses suggest that these chronologic descriptors are valid. Our findings confirmed that psychosis associated with epilepsy should not be defined as a single, simple condition but rather as a complex condition with several possible subcategories.
Do Nonspecific Focal EEG Slowing and Epileptiform Abnormalities Favor One Hemisphere?
Authors: Doherty Michael J. , Walting Paul J. , Morita Denise C. , Peterson Rich A. , Miller John W. , Holmes Mark D. , Watson Nathaniel F.
Published: March 2003

Summary:  Purpose: Several EEG‐based studies suggest that epileptiform activity originates from the left more than the right hemisphere. In contrast, other pathophysiologies such as stroke lateralize relatively symmetrically. Study of focal slowing and other EEG abnormalities allows assessment of favoring as well as referral and interpretation bias.

Methods: The 1,331 consecutive adult EEG reports were reviewed for epileptiform discharges (EDs) and nonepileptiform focal slowing. Side of slowing or EDs, interpreting electoencephalographer, and whether the patient was undergoing long‐term monitoring or routine EEG were tallied. Results were statistically analyzed.

Results: Focal slowing occurred symmetrically; EDs favored the left hemisphere (p < 0.01).

Conclusions: The left hemisphere may be more prone to epileptiform abnormalities in adults, but not to the nonspecific pathophysiologic processes that cause slowing. These findings suggest that potential interpretation bias does not influence left hemispheric favoring of EDs and instead may implicate a biologic etiology.
Video‐EEG Monitoring in the Elderly: A Review of 94 Patients
Authors: McBride Alexandra E. , Shih Tina T. , Hirsch Lawrence J.
Published: March 2003

Summary:  Purpose: We sought to determine the utility and results of video‐EEG monitoring in elderly patients. There is an increased incidence of epilepsy in the elderly population. Few studies have assessed the characteristics of epileptic and nonepileptic seizures in this age group. Diagnostic evaluation with video‐EEG monitoring is a means to distinguish these different types of events.

Methods: The authors reviewed all patients aged 60 years and older who were admitted to the epilepsy monitoring unit at Columbia–Presbyterian Medical Center from January 21, 1991, to April 12, 1999.

Results: A total of 94 patients and 99 patient admissions were identified, accounting for 8% of all admissions. The average age was 70 years, and the mean length of stay was 3.8 days. Typical events were recorded in 75 of the 99 patient admissions. A total of 118 seizures was recorded in 46 patients, and 98 nonepileptic events were seen in 27 patients. Of the patients with nonepileptic events, 13 had psychogenic seizures. The majority of patients with nonepileptic events were taking antiepileptic medication. Whereas 76% of the patients with epileptic events had interictal epileptiform discharges, 26% of the patients with nonepileptic events had epileptiform discharges as well.

Conclusions: Video‐EEG monitoring in the elderly leads to a definitive diagnosis in the majority of patients in a relatively short time. Interictal recordings are inadequate in determining the nature of paroxysmal events. Nonepileptic events are common in the elderly, including psychogenic seizures, and these are often misdiagnosed and mistreated as epileptic seizures.
Lidocaine‐dependent Early Infantile Status Epilepticus with Highly Suppressed EEG
Authors: Sawaishi Yukio , Yano Tamami , Enoki Masamichi , Takada Goro
Published: March 2003

Summary: We report an early infantile patient characterized by intractable hyponatremia, progressive megalencephaly, and epileptic seizures with an EEG pattern that alternated between interictal low‐voltage background and ictal burst activity. Repeatedly all the abnormal findings improved in a lidocaine‐dependent manner. Given the pharmacologic mechanisms of lidocaine as a sodium channel blocker, we speculate that our patient had a sodium channel dysfunction.
Treatment of Refractory Status Epilepticus with Pentobarbital, Propofol, or Midazolam: A Systematic Review
Authors: Claassen Jan , Hirsch Lawrence J. , Emerson Ronald G. , Mayer Stephan A.
Published: March 2003

Summary:  Background: New continuous infusion antiepileptic drugs (cIV‐AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients.

Methods: We performed a literature search of studies describing the use of MDL, PRO, or PTB for the treatment of RSE published between January 1970 and September 2001, by using MEDLINE, OVID, and manually searched bibliographies. We included peer‐reviewed studies of adult patients with SE refractory to at least two standard AEDs. Main outcome measures were the frequency of immediate treatment failure (clinical or electrographic seizures occurring 1 to 6 h after starting cIV‐AED therapy) and mortality according to choice of agent and titration goal (cIV‐AED titration to “seizure suppression” versus “EEG background suppression”).

Results: Twenty‐eight studies describing a total of 193 patients fulfilled our selection criteria: MDL (n = 54), PRO (n = 33), and PTB (n = 106). Forty‐eight percent of patients died, and mortality was not significantly associated with the choice of agent or titration goal. PTB was usually titrated to EEG background suppression by using intermittent EEG monitoring, whereas MDL and PRO were more often titrated to seizure suppression with continuous EEG monitoring. Compared with treatment with MDL or PRO, PTB treatment was associated with a lower frequency of short‐term treatment failure (8 vs. 23%; p < 0.01), breakthrough seizures (12 vs. 42%; p < 0.001), and changes to a different cIV‐AED (3 vs. 21%; p < 0.001), and a higher frequency of hypotension (systolic blood pressure <100 mm Hg; 77 vs. 34%; p < 0.001). Compared with seizure suppression (n = 59), titration of treatment to EEG background suppression (n = 87) was associated with a lower frequency of breakthrough seizures (4 vs. 53%; p < 0.001) and a higher frequency of hypotension (76 vs. 29%; p < 0.001).

Conclusions: Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV‐AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.
Temporal Lobe Epilepsy Surgery: Outcome, Complications, and Late Mortality Rate in 215 Patients
Authors: Salanova V. , Markand O. , Worth R.
Published: March 2003

Summary:  Purpose: We studied the surgical outcome, complications, and the late mortality rate in a large group of patients with medically refractory temporal lobe epilepsy (TLE).

Methods: Two‐hundred fifteen patients with TLE were treated surgically between 1984 and 1999 after a comprehensive presurgical evaluation. Patients were followed up at 6 weeks, 3–6 months, and yearly thereafter. In addition, questionnaires were sent on the anniversary of their surgery. Surgical outcome (Engel's classification), complication rate, and factors contributing to late mortality were analyzed. Standardized mortality ratios (SMRs) were calculated.

Results: There was no surgical mortality. Two (0.9%) had mild hemiparesis, one (0.4%) had a hemianopia, seven (3.2%) had transient cranial nerve palsies, and eight (3.7%) had transient postoperative language difficulties. One hundred forty‐eight (69%) became seizure free, 43 (20%) had rare seizures, 14 (6.5%) had worthwhile seizure reduction, and 10 (4.6%) had no improvement (follow‐up, 1–15 years). Three (2%) of 148 seizure‐free patients died during follow‐up, compared with eight (11.9%) of 67 not seizure‐free patients. The mean duration of epilepsy before surgery for the surviving patients was 17.8 years, and for those patients who died, 25.9 years (p < 0.05). Six (5.7%) of 104 patients with right‐sided resections died during follow‐up, compared with five (4.5%) of 111 with left‐sided resections.

Conclusions: Eighty‐nine percent of patients became seizure free or had rare seizures, with low morbidity, and no surgical mortality. The late mortality occurred predominantly in patients with persistent seizures (SMR, 7.4). Those patients who died had a longer duration of epilepsy before surgery. In contrast, among those patients who became seizure free, the mortality rate was much lower, and similar to the general population of Indiana (SMR, 1.7).
Mild Generalized Epilepsy and Developmental Disorder Associated with Large Inv Dup(15)
Authors: Chifari Rosanna , Guerrini Renzo , Pierluigi Mauro , Cavani Simona , Sgrò Vincenzo , Elia Maurizio , Canger Raffaele , Canevini Maria Paola
Published: March 2003

Summary:  Purpose: Several studies attempted to clarify the genotype–phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader–Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult‐onset epilepsy. This report may help to define the milder spectrum of the syndrome.

Methods: A 25‐year‐old girl with mild mental retardation had a 6‐year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike–wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27‐year‐old man with mild mental retardation, had a 5‐year history of rare generalized tonic–clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video‐EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control.

Results: Molecular analysis revealed a large inv dup15 in both patients.

Conclusions: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear‐cut etiology.