bluuebunny/crossref_metadata_2025 huggingface dataset:
Cause‐Specific Mortality in Epilepsy: A Cohort Study of More Than 9,000 Patients Once Hospitalized for Epilepsy
Authors: Nilsson Lena , Tomson T. , Farahmand B. Y. , Diwan V. , Persson P. G.
Published: August 2005

Summary: Purpose: We studied overall and cause‐specific mortality rates in a large cohort of patients with epilepsy compared with mortality rates of the general population in the same geographic area.

Methods: The cohort consisted of all patients (N = 9,061) aged >15 years admitted with a diagnosis of epilepsy for inpatient care in Stockholm during the years 1980–1989. All patients were followed in the National Cause‐of‐Death Register, from which the causes of death were obtained, until December 31, 1992. Thus, 53,520 person‐years were observed. Mortality rates were compared with those of the general population of Stockholm.

Results: We observed 4,001 deaths in the cohort, compared with an expected number of 1,109 deaths in the general population. This yielded a standardized mortality ratio (SMR) of 3.6 [95% confidence interval (CI) 3.5–3.71] Although highest in the younger patients, the SMR was significantly increased in all age groups. The excess mortality rate in the cohort was due to a wide range of causes of death, including malignant neoplasms [SMR 2.6 (2.4–2.8)], diseases of the circulatory system, [SMR 3.1 (3.0–3.3)], diseases of the respiratory system [SMR 4.0 (3.64.5)], diseases of the digestive system [SMR 5.1 (4.4–5.8)], and injuries and poisoning [SMR 5.6 (5.0–6.3)].

Conclusions: Our results demonstrate that this large subgroup of patients with a diagnosis of epilepsy, once hospitalized and discharged, is a population at risk, with an excess mortality rate due to several different causes.
Central Benzodiazepine/γ‐Aminobutyric AcidA Receptors in Idiopathic Generalized Epilepsy: An [11C]Flumazenil Positron Emission Tomography Study
Authors: Koepp Matthias J. , Richardson Mark P. , Brooks David J. , Cunningham Vin J. , Duncan John S.
Published: August 2005

Summary: Purpose: Previous [11C]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in central benzodiazepine γ‐aminobutyric acid, (GABAA) receptor (cBZR) binding or focal decreases in the thalamus and increases in the cerebellar nuclei with no changes in cerebral cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE patients treated with valproate (VPA) than in cerebral cortex of controls. We now report high‐resolution three‐dimensional [11C]FMZ PET studies in a larger number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudinal design to determine the functional effect of VPA.

Methods: We compared parametric images of [11C]FMZ volume of distribution (FMZVD) in 10 IGE patients before and after addition of VPA and in 20 normal subjects.

Results: Mean FMZVD was significantly higher in the cerebral cortex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal controls. Using statistical parametric mapping, no significant areas of focal abnormality of FMZVD were detected. Addition of VPA was not associated with a significant change in mean FMZVD in any brain area.

Conclusions: Our finding of increased FMZVD in IGE could reflect microdysgenesis or a state of cortical hyperexcitability. Our data suggest that short‐term VPA therapy does not affect the number of available cBZR in patients with IGE.
Significance of Spikes Recorded on Intraoperative Electrocorticography in Patients with Brain Tumor and Epilepsy
Authors: Tran Teresa A. , Spencer Susan S. , Javidan Manoucher , Pacia Steven , Marks David , Spencer Dennis D.
Published: August 2005

Summary: Purpose: Patients with medically intractable epilepsy due to brain tumors may undergo resective surgery for treatment of both the tumor and the epilepsy. In this instance, the extent of surgical resection is sometimes guided by spikes recorded on intraoperative electrocorticography (ECoG). Whether spikes recorded by electrocorticography imply active epileptogenicity has not been addressed adequately.

Methods: We performed preresection and postresection electrocorticography on 36 patients with brain tumor and seizures. There were 3 I low‐grade gliomas, 4 high grade gliomas, and 1 dysembryonic neuroepithelial tumor. Patients had resection of the tumor to normal tissue margins only. No additional surgery was performed, based on electrocorticography findings. Patients were divided into 2 groups: Group I (no seizures or rare seizures after resection) and Group I1 (recurrent seizures). Recorded spikes were analyzed for spike distribution and spike discharge rate.

Results: On preresection ECoG, 85% of patients in Group I and 88% of patients in Group I1 had spikes. In Group I, 70% of patients had spikes over the tumor bed, and 63% of patients had spikes in the surrounding tissue. In Group 11, 55% of patients had spikes over the tumor bed and 89% of patients had spikes in the surrounding tissue. Spike distribution and discharge rate did not correlate with outcome. On postresection ECoG, 60% of patients in Group I and 67% of patients in Group II had residual spikes. In Group I, 46% of patients had spikes along the margin of resection and 26% of patients had extramarginal spikes. In Group 11, 50% had spikes along the margin of resection and 67% of patients had extramarginal spikes.

Conclusions: The difference in spike distribution in the extramarginal area between the 2 groups was not statistically significant, but showed a trend toward a relationship between postresection spikes and seizure recurrence.
Development of Hippocampal Atrophy: A Serial Magnetic Resonance Imaging Study in a Patient Who Developed Epilepsy After Generalized Status Epilepticus
Authors: Wieshmann Udo C. , Woermann F. G. , Lemieux L. , Free S. L. , Bartlett P. A. , Smith S. J. M. , Duncan J. S. , Stevens J. M. , Shorvon F. D.
Published: August 2005

Summary: Purpose: To investigate changes in hippocampal volume.

Methods: We used serial magnetic resonance imaging (MRI) in a patient who developed chronic epilepsy after having generalized tonic‐clonic status epilepticus (SE). Five MRI investigations were performed during SE and a 58‐month follow‐up period. Hippocampal volumetric measurements and coregistration of scans were performed to detect hippocampal atrophy.

Results: During status both mesiotemporal regions returned a high signal on T,‐weighted images. Two months after the onset of SE, bilateral hippocampal atrophy was detected. Further progressive hippocampal atrophy was detected in the subsequent 58 months by both hippocampal volumetric measurements and coregistration of scans.

Conclusions: Our findings suggest that hippocampal atrophy is a process that may continue after the end of the SE.
Failure of Absorption of Gabapentin After Rectal Administration
Authors: Kriel Robert L. , Birnbaum Angela K. , Cloyd James C. , Ricker Beverly J. , Saete Carolyn Jones , Caruso Kimberly J.
Published: August 2005

Summary: Purpose: We wished to determine the extent of absorption of gabapentin (GBP) after rectal administration to children on maintenance therapy.

Methods: Two children scheduled for extensive surgery received GBP rectally and orally. A pharmacokinetic profile was derived after each route of administration.

Results: Serum GBP levels after rectal administration decreased at a rate similar to their rate of decrease after oral administration. However, GBP concentrations were much lower after rectal administration; therefore, we concluded that the aqueous solution was poorly absorbed rectally. The GBP half–life (t1/2) for the 2 children after oral doses were 4.2 and 4.8 h.

Conclusions: Rectal administration of GBP is not satisfactory when oral administration is interrupted. When oral GBP therapy is temporarily discontinued, clinicians should consider administration of alternative antiepileptic drugs (AEDs) that can be administered parenterally or rectally.
Comparative Epidemiology of Epilepsy in Pakistan and Turkey: Population‐Based Studies Using Identical Protocols
Authors: Aziz H. , Güvener A. , Akhtar S. W. , Hasan K. Z.
Published: August 2005

Summary: Purpose: To determine comparative prevalence rates, demographics, phenomenology, seizure classification, presumptive etiology, treatment status, and selected socioan‐thropological aspects of epilepsy in Pakistan and Turkey.

Methods: A population‐based, cross‐cultural comparative study of epilepsy was designed with identical protocols to be performed simultaneously in Pakistan and Turkey. The essential feature of the design was an unselected population, with reference to their previous medical contact, and use of standardized International Community‐Based Epilepsy Research Group (ICBERG) protocols to assess cross‐cultural differences.

Results: In all, 24,130 persons in Pakistan and 11,497 persons in Turkey (both urban and rural, of all ages and both sexes) were studied. The crude prevalence rate of epilepsy was 9.98 in 1,000 in Pakistan and 7.0 in 1,000 in Turkey (14.8 in 1,000 in rural and 7.4 in 1,000 in urban areas of Pakistan; 8.8 in 1,000 in rural and 4.5 in 1,000 in urban areas of Turkey). In both countries, epilepsy was twice as prevalent in rural areas than in urban areas. Mean age of onset of epilepsy was 13.3 years in Pakistan and 12.9 years in Turkey. Overall frequency of seizure types was similar in both countries, with no urban/rural differences. The frequency distribution in Pakistan and Turkey, respectively, was as follows: generalized tonic‐clonic, 80.5 and 65.4%; simple partial, 5 and 7.4%; complex partial, 5 and 12.3%; generalized absence, 0.8 and 4.9%; tonic and atonic, 5.8 and 3.7% each; and myoclonic, 5.8 and 1.2%. A putative cause for the epilepsy could be attributed in 38.4% of cases in Pakistan and 35.7% of cases in Turkey. Only 3% of patients in Pakistan, but 71% of patients in Turkey, believed that their illness was due to supernatural causes. The treatment status was very poor. In Pakistan, 27.5% of people with epilepsy in urban areas and 1.9% of people with epilepsy in rural areas were receiving antiepileptic drugs (AEDs) at the time of the survey. In, Turkey 30% of patients were receiving AEDs (marginally higher in rural areas).

Conclusions: The prevalence of epilepsy is slightly higher in Pakistan than in Turkey; some marginal differences in age and sex distribution, are not statistically significant. The results are comparable to those in Ecuador, where the same epidemiologic protocol was used.
Protective Effect of Zonisamide, an Antiepileptic Drug, Against Transient Focal Cerebral Ischemia with Middle Cerebral Artery Occlusion‐Reperfusion in Rats
Authors: Minato Hisao , Kikuta Chie , Fujitani Buichi , Masuda Yoshinobu
Published: August 2005

Summary: Purpose: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats.

Methods: Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3‐0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloridenegative stained area of the serial brain sections 1 day after MCAo.

Results: The pre‐ or postischemic treatment with ZNS [(10–100 mgkg P.o.), 30 min before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mgkg p.0. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (VPA 1,000 mgkg p.o. twice) also had no effect.

Conclusions: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.
Maternal Use of Antiepileptic Drugs and the Risk of Major Congenital Malformations: A Joint European Prospective Study of Human Teratogenesis Associated with Maternal Epilepsy
Authors: Samrén E. B. , van Duijn C. M. , Koch S. , Hiilesmaa V. K. , Klepel H. , Bardy A. H. , Mannagetta G. Beck , Deichl A. W. , Gaily E. , Granström I. L. , Meinardi H. , Grobbee D. E. , Hofman A. , Janz D. , Lindhout D.
Published: August 2005

Summary: Purpose: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and poly‐therapy.

Methods: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies.

Results: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2–4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6–15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3–18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4–67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1–57.6). Offspring of mothers using > 1,000 mg VPNday were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed ≥600 mg VPNday (RR 6.8; 95% CI: 1.4–32.7). No difference in risk of MCA was found between the offspring exposed to 601–1,000 mg/day and ≥600 mg/day.

Conclusions: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population‐based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.
Changes in Regional Cerebral Blood Flow Beyond the Temporal Lobe in Unilateral Temporal Lobe Epilepsy
Authors: Rabinowicz Adrian L. , Salas Ezequiel , Beserra Felix , Leiguarda Ramon C. , Vazquez Silvia E.
Published: August 2005

Summary: Purpose: Single photon emission computed tomography (SPECT) is widely used to evaluate functional abnormalities during the epileptic event. Changes in regional cerebral blood flow (rCBF) are well defined in patients with temporal lobe epilepsy (TLE) undergoing surgical resection. Nonetheless, the interpretation of ictal abnormalities in CBF beyond the temporal lobes has not been carefully addressed.

Methods: We assessed 4 patients with pathologically proven unilateral TLE who had significant ipsilateral frontal hypoperfusion in ictal studies with no other abnormalities but chronic epilepsy accounting for such findings. Patients were assessed as candidates for surgery by interictal EEG, neuropsychological studies, brain magnetic resonance imaging, scalp electrode video‐EEG monitoring, and ictal SPECT.

Results: Characteristic hyperperfusion was evident over the temporal lobe ipsilateral to the EEG focus, with significant hypoperfusion over the frontal region in 3 patients. In patient 4, frontal hypoperfusion was not statistically significant.

Conclusions: SPECT demonstrated relative rCBF changes beyond the epileptogenic zone in unilateral TLE. Our findings provide further insight into the pathophysiological changes underlying this condition.
Olfactory Prodromal Symptoms and Unilateral Olfactory Dysfunction Are Associated in Patients with Right Mesial Temporal Lobe Epilepsy
Authors: Lehrner J. , Baumgartner C. , Serles W. , Olbrich A. , Pataraia E. , Bacher J. , Aull S. , Deecke L.
Published: August 2005

Summary: Purpose: We report a patient with mesial temporal lobe epilepsy (MTLE) with olfactory prodromal symptoms manifested as an unpleasant smell of onions, who was found to have an ipsilateral deficit of olfactory naming (olfactory agnosia).

Methods and Results: Preoperative olfactory testing revealed a selective right‐sided olfactory deficit for naming of odors. Olfactory threshold was within the normal range. The patient has been seizure free after selective amygdalohippocampectomy for 4 months. No olfactory prodromal events have occurred since surgery. Olfactory testing 3 months after resection showed that right‐sided odor naming was still impaired.

Conclusions: We conclude that olfactory prodromal symptoms may be associated with unilateral olfactory dysfunction, and lateralization of seizure origin may be possible by unilateral olfactory testing.
Phenytoin‐Induced Teratogenesis: A Molecular Basis for the Observed Developmental Delay During Neurulation
Authors: Bennett Gregory D. , Lau Franciscus , Calvin James A. , Finnell Richard H.
Published: August 2005

Summary: Purpose: We wished to determine whether chronic phenytoin (PHT) exposure could impair neural development and if any morphological alterations could be linked to changes in gene expression.

Methods: Pregnant SWV mice were chronically administered PHT 40 mgkglday from gestational day (GD) 0:12 (day:h) until they were killed at various timepoints throughout neural tube closure (NTC). At each timepoint, embryos from both treated and control dams were collected and scored for their progression through NTC. The neural tubes were then isolated and subjected to in situ transcription (IST) and antisense RNA amplification procedures. Using these techniques, we examined the expression of 10 genes: N‐cadherin (Ncad), collagen type IV (col‐IV), bcl‐2, c‐jun, PAX‐3, collular retinol binding protein‐2 (CRBP‐2), retinoic acid receptor a (RARα), transforming growth factorβ2, (TGFβ2), wee‐1, and EMX‐2.

Results: Chronic PHT exposure not only caused a delay in NTC whereby exposed embryos lagged behind the controls at each collection timepoint, but also significantly altered the expression of specific genes at distinct times during NTC. Early in NTC, PHT induced a significant reduction in the expression of N‐cad, col‐IV, and c‐jun in exposed embryos as compared with controls. In contrast, during the midstages of NTC, the only significant molecular alterations observed in the PHT‐exposed embryos was the continued decreased expression of col‐IV and an increase in CRBP‐2 expression. Finally, in the latter stages of NTC, PHT caused a significant reduction in the expression of bcl‐2, RARα, TGFβ2, EMX‐2, and PAX‐3.

Conclusions: These results show that although the effects of PHT are morphologically subtle, causing a delay in the development of the neural tube, this delay is accompanied by alterations in critical genes at crucial times of neural development that may account for the observed neurological deficits often associated with PHT exposure.
Physical Activity, Heath‐Related Fitness, and Health Experience in Adults with Childhood‐Onset Epilepsy: A Controlled Study
Authors: Jalava Merja , Sillanpaa Matti
Published: August 2005

Summary: Purpose: To show any possible associations between childhood‐onset epilepsy and physical activity, health‐related fitness, and health experience.

Methods: A population‐based cohort of 176 patients with epilepsy since childhood was monitored for a mean of 35 years. Patients with recurrent, unprovoked epileptic seizures with no associated initial neurologic impairment or disability, termed those with “epilepsy only” (n = 100), were compared with matched controls for self‐reported physical activity, health experience, laboratory tests, body mass index, and muscle power tests.

Results: On the basis of muscle tests, physical fitness proved to be significantly poorer in patients with “epilepsy only” than in matched controls. During the preceding year, 22% of patients and 24% of controls had reduced their physical activities because of some illness; only 2% reduced their physical activities because of epilepsy. No significant difference was found in blood status, except for a lower serum creatinine level in the patients. Current antiepileptic drug (AED) therapy appeared significantly associated with lower hemoglobin and creatinine levels and higher highdensity lipoprotein values. The patients perceived their health status to be comparable with that of controls, irrespective of physical inactivity, continued seizures, or AED monotherapy. However, patients receiving AED polytherapy perceived their health as rather poor or very poor significantly more often than did controls.

Conclusions: Based on objective muscle tests, adults with childhood‐onset “epilepsy only” have poorer physical fitness than do matched controls, but they have a feeling of good personal health.
Pharmacokinetics and Safety of Tiagabine in Subjects with Various Degrees of Hepatic Function
Authors: Lau Alan H. , Gustavson Linda E. , Sperelakis Rita , Lam Nancy P. , El‐Shourbagy Tawakol , Qian Jiang X. , Layden Thomas
Published: August 2005

Summary: Purpose: To evaluate the pharmacokinetics and safety of multiple oral doses of tiagabine HC1 in subjects with different degrees of hepatic impairment.

Methods: Four subjects with mild hepatic impairment, three subjects with moderate hepatic impairment, and six matched normal subjects received twice daily oral tiagabine HCl for 5.5 days. Serial blood specimens were obtained for 48 h after the final dose. Total and unbound tiagabine plasma concentrations were determined by high‐performance liquid chromatography (HPLC) and ultrafiltration, respectively. Pharmacokinetic parameters were compared between the groups by analysis of covariance.

Results: For total tiagabine concentrations in normal subjects and subjects with mild and moderate hepatic impairment, Cmax values (mean i SD) were 117 ± 54, 172 ± 40, and 172 ± 28 ng/ml; Cmin values were 13 ± 4,27 ± 4, and 28 ± 6 ng/ml; areas under the plasma concentration‐time curve were 396 ± 59, 633 ± 16, and 675 ± 32 ng Wml, and elimination half‐lives (harmonic means) were 7, 12, and 16 h, respectively. Unbound tiagabine coricentrations, area under the unbound plasma concentration‐time curve, and the free fractions were increased in the hepatically impaired subjects. Reduced serum albumin and α1‐acid glycoprotein concentrations may have contributed to increases in the unbound fraction. Adverse events observed included dizziness, tremor, nausea, somnolence, incoordination, and unsteady gait. The frequency of these events was increased in the subjects with liver impairment.

Conclusions: Because of the decreased drug elimination caused by liver function impairment, reduced doses or increased dosing interval or both may be needed to attain therapeutic plasma drug concentrations. Time to reach steady state also may be prolonged. The patients should be monitored closely for potential neurologic adverse events.
Clonidine and Methohexital‐Induced Epileptic Magnetoencephalographic Discharges in Patients with Focal Epilepsies
Authors: Kirchberger K. , Schmitt H. , Hummel C. , Peinemann A. , Pauli E. , Kettenmann B. , Stefan H.
Published: August 2005

Summary: Purpose: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings for focus localization. To increase the number of epileptic discharges required for MEG analysis, we administered methohexital (MHT), a short‐acting barbiturate known to provoke epileptic activity. We also investigated the spike‐provoking properties of clonidine in comparison with MHT.

Methods: Patients were briefly anesthetized with intravenously administered MHT after being premedicated orally with clonidine. Numbers and locations of epileptic MEG discharges were assessed after clonidine premedication as well as during MHT anesthesia. Results were compared with baseline MEG recordings.

Results: MHT increased the frequency of focal epileptic discharges in 8 of 13 patients (1 of the 14 patients did not receive MHT after premedication with clonidine). Premedication with clonidine also increased focal epileptic discharges in 9 of 14 patients. The numbers of epileptic signals and numbers of spikes contributing to MEG source localizations were significantly increased in MEG recordings under both treatment conditions (clonidine premedication and MHT anesthesia) as compared with baseline MEG recordings.

Conclusions: Our results confirmed the selective proconvulsive effects of MHT on the epileptic focus, as previously suggested by EEG and electrocorticographic (ECoG) investigations. However, our present data establish for the first time that clonidine increases epileptic activity in patients with seizure disorders and indicate that clonidine is suitable as an activating agent for localization of epileptogenic foci by MEG. This effect of clonidine on specific epileptic activity also indicates that specific care must be taken when clonidine is used as an antihypertensive drug in patients with seizure disorders.
Rolandic Epilepsy: An Incidence Study in Iceland
Authors: Astradsson Arnar , Olafsson Elias , Ludvigsson Petur , Björgvinsson Hilmar , Hauser W. Allen
Published: August 2005

Summary: Purpose: We wished to determine incidence, clinical features, and prognosis of benign rolandic seizures (BRS) and benign rolandic epilepsy (BRE) in a total population.

Methods: Cases were ascertained through review of all EEG records, and diagnosis was verified by review of medical records. Follow‐up information regarding seizures and treatment was obtained from parents and treating physicians.

Results: In the Icelandic population aged 3–15 years, the incidence of BRS is 6.2 and BRE 4.7 in 100,000. Five years after onset 95% were seizure‐free. At last follow‐up, all were seizure free and had not been treated with antiepileptic drugs (AEDs) for at least 1 year.

Conclusions: Our study demonstrates that BRS is a common entity in children. The prognosis is excellent and treatment is not necessary in all cases. It is important to identify BREBRS correctly and distinguish it from other types of epilepsy.
Epilepsy in Patients with Multiple Sclerosis: Radiological‐Clinical Correlations
Authors: Moreau Th. , Sochurkova D. , Lemesle M. , Madinier G. , Billiar Th. , Giroud M. , Dumas R.
Published: August 2005

Summary: Purpose: To determine potential mechanisms of epilepsy in patients with multiple sclerosis (MS).

Methods: Among 402 patients with clinically and radiologically defined MS, including de novo cases, presenting to the Neurology Service, University Hospital of Dijon, we identified 17 with epileptic seizures (4.25%). Among them, the percentage with partial seizures (50%) was greater than that in the reference population.

Results: In most of the patients with MS, plaques were localized in the frontal region, associated with frontal and callosal atrophy, a frontal syndrome, and severe disability status (as assessed by a standard scale). Magnetic resonance imaging (MRI) showed numerous subcortical plaques. Seizures generally were well controlled with antiepileptic drugs (AEDs).

Conclusions: Our data suggest that the subcortical plaques of MS underlie seizure activity in patients with MS and epilepsy.
Long‐Term Survival of People with Unprovoked Seizures: A Population‐Based Study
Authors: Olafsson Elias , Allen Hauser W. , Gudmundsson Gunnar
Published: August 2005

Summary: Purpose: Few population‐based studies of longterm survival in people with seizures or epilepsy have been made.

Methods: Between January 1, 1960 and December 31, 1964, we identified 224 incidence cases of unprovoked seizures in Iceland and determined survivorship status and date of death for the cases as of January 1, 1996. We compared survivorship with that expected based on data from age‐/sex‐specific life tables from the country for 1961–1990 and calculated the standardized mortality ratio (SMR).

Results: By 30 years after diagnosis, there were 45 deaths among patients with unprovoked seizures as compared with an expected 28 deaths [standardized mortality ratio (SMR) 1.6; 95% confidence interval (CI) 1.2–2.21. Patients with unprovoked seizures of unknown etiology did not have a significant increase in mortality overall (SMR 1.3, 95% CI 0.8–1.9) or in any time interval. For patients with remote symptomatic un provoked seizures, mortality was increased (SMR 2.3, 95% CI 1.4–3.5). This increase was attributable to excess mortality for the first 15 years after diagnosis (SMR 4.1, 95% CI 2.4–6.6), and SMR was not different after that time.

Conclusions: Survivorship was decreased for the population of patients with unprovoked seizures. The increased mortality was primarily due to excess mortality in patients with remote symptomatic seizures, occurring in the first 15 years after diagnosis. Overall mortality for idiopathic unprovoked seizures was not significantly increased.
Status Epilepticus Causes Long‐Term NMDA Receptor‐Dependent Behavioral Changes and Cognitive Deficits
Authors: Rice Ann C. , Floyd Candace L. , Lyeth Bruce G. , Hamm Robert J. , DeLorenzo Robert J.
Published: August 2005

Summary: Purpose: The role of N‐methyl‐d‐aspartate (NMDA)‐receptor activation on behavioral and cognitive changes after status epilepticus (SE) is unknown. In this study, behavioral and cognitive changes after SE were evaluated in the short and long term and in rats in which the NMDA receptor was inactivated during SE.

Methods: Pilocarpine (350 mg/kg) was injected to induce SE. Inhibition of the NMDA receptor during SE was achieved with MK‐801 (4 mg/kg). Seizure intensity during SE was monitored by electroencephalography (EEG). After SE, behavioral studies were performed to identify abnormal behavior by using behavioral tests adapted from Moser's funetional observational battery. Cognitive changes were assessed by using the Morris Water Maze (MWM).

Results: Pilocarpine–treated animals scored significantly higher on two of the behavioral tests: the Touch test and the Pick‐Up test. These behavioral changes occurred very soon after SE, with the earliest changes observed 2 days after SE and persisting for the life of the animal. Inhibition of the NMDA receptor with MK‐801 completely inhibited these behavioral changes under conditions that did not alter the duration of SE. In addition, pilocarpine‐treated animals exhibited cognitive deficits as determined by using the MWM. Six weeks after SE, the animals displayed significantly longer latencies to locate the hidden platform on this test. The impaired performance on the MWM also occurred as early as 5 days after SE. These cognitive deficits were prevented in animals treated with MK‐801 during SE.

Conclusions: The results indicate that behavioral and cognitive changes occur soon after SE, are permanent, and are dependent on NMDA‐receptor activation during SE. NMDA receptor activation may play an important role in causing cognitive and behavioral morbidity after recovery from SE.
Effects of Phenytoin, Carbamazepine, and Gabapentin on Calcium Channels in Hippocampal Granule Cells from Patients with Temporal Lobe Epilepsy
Authors: Schumacher Thekla B. , Beck Heinz , Steinhauser Christian , Schramm Johannes , Elger Christian E.
Published: August 2005

Summary: Purpose: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage‐dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy.

Methods: Acutely isolated human hippocampal granule cells were examined by using the whole‐cell configuration of the patch‐clamp technique.

Results: PHT and CBZ produced a reversible, concentrationdependent inhibition of high‐voltagectivated (HVA) Ca2+ currents without affecting voltage‐dependent activation. The concentration‐response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with halfmaximal inhibition being obtained at 89 and 244 μM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole‐brain concentration of 80 μM. In ontrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady‐state inactivation. PHT, 80 μ4, shifted the potential of half‐maximal inactivation by ‐3.1 ± 0.5 mV (p < 0.05). GBP, which was recently found to bind to the à2 subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances.

Conclusions: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.
Interictal Cardiovascular Autonomic Responses in Patients with Epilepsy
Authors: Isojärvi Jouko I. T. , Ansakorpi Hanna , Suominen Kalervo , Tolonen Uolevi , Repo Marja , Myllylä Vilho V.
Published: August 2005

Summary: Purpose: To evaluate the interictal autonomic nervous system function in 84 patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy, and 47 patients receiving long‐term carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure disorder.

Methods: We assessed autonomic control of the cardiovascular regulatory system, by standardized cardiovascular reflex tests measuring changes in heart rate (HR) and blood pressure (BP) at rest and after certain stimuli.

Results: The HR and BP responses were similar to those of control subjects in patients with newly diagnosed epilepsy. However, HR variation during normal breathing and maximum systolic BP increase in isometric work were diminished in patients, who had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time. Diminished HR responses to the Valsalva maneuver were noted in patients receiving CBZ as monotherapy and during deep breathing in patients receiving CBZ combined with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses in isometric work. When analyzed in relation to epilepsy type, suppressed HR responses in normal breathing were associated with primary generalized epilepsy (PGE), whereas diminished BP responses in isometric work were associated with partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1 patient receiving long‐term CBZ monotherapy for partial epilepsy had two abnormal cardiovascular response test results.

Conclusions: Our results show that cardiovascular responses mediated by both the parasympathetic and sympathetic nervous system are diminished in patients with epilepsy. However, the changes appear to be clinically significant in only a few of them and appear to be associated with CBZ medication. Further studies are needed to detect the underlying complex interactions and clinical significance of autonomic nervous system dysfunction in patients with epilepsy.
Nonepileptic Posttraumatic Seizures
Authors: Barry Elizabeth , Krumholz Allan , Bergey Gregory K. , Chatha Herlene , Alemayehu Shimellis , Grattan Lynn
Published: August 2005

Summary: Purpose: Epileptic posttraumatic seizures (PTSs) are a well‐recognized consequence of head injury (HI), but HI and nonepileptic seizures (NESs) have not been related. We describe a significant subset of patients with NESs who had their seizures attributed to HI.

Methods: We reviewed the records of all patients diagnosed with NES at the University of Maryland Medical Center over a 6‐year period (1989–1995) and selected patients with seizures attributed to a head injury occurring ≥3 years before the onset of their seizures.

Results: Of 157 patients with video‐EEG confirmed NES, 37 (24%) had the onset of their seizures attributed to an HI. Their average age was 34 years (range, 15–56 years); 68% were women. Nonepileptic PTS usually developed within the first year after HI (89%). Convulsive symptoms were present in 54%. Whereas epileptic PTSs characteristically follow severe HI, the majority (78%) of our patients with nonepileptic PTSs sustained only mild HI. Before their HI, 76% of our patients were employed, working in the home, or students, but only 11% could continue those activities after developing nonepileptic PTSs.

Conclusions: Nonepileptic PTSs are frequently mistaken for epileptic PTSs and result in serious disability. The misdiagnosis of nonepileptic PTSs leads to ineffective and inappropriate treatment. Patients with intractable seizures after HIS, articularly mild HIS, should be carefully evaluated for NESs.
Lamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy
Authors: Guerrini Renzo , Dravet Charlotte , Genton Pierre , Belmonte Anna , Kaminska Anna , Dulac† Olivier
Published: August 2005

Summary: Purpose: In severe myoclonic epilepsy of infancy (SME), multiple drug‐resistant focal and generalized seizure types occur. Lamotrigine (LTG), found effective in many generalized and partial seizures, has been little used in severe childhood epilepsy syndromes with multiple seizure types. We studied the effects of LTG in SME.

Methods: Twenty‐one patients with SME, aged 2–18 years, were treated with LTG, 20 in add‐on and one in monotherapy. LTG was started at 0.2–2.5 mg/kg/day and increased to 2.5–12.5 mg/kg/day. For each seizure type, excluding atypical absences, >50% variations compared with the 2 months preceding LTG were considered indicators of response, also taking into account the degree of disability each seizure type produced.

Results: LTG induced worsening in 17 (80%) patients, no change in three, and improvement in one. There was >50% increase in convulsive seizures in eight (40%) of 20 patients. Myoclonic seizures worsened in six (33%) of 18 patients. Of five patients improving in at least one seizure type, four had concomitant worsening of more invalidating seizures. Clear‐cut worsening appeared within 3 months in most patients but was insidious in some. LTG was suspended in 19 patients after 15 days‐5 years (mean, 14 months) with consequent improvement in 18.

Conclusions: The pronounced seizure deterioration during LTG treatment was not attributable to the natural course of the disease and could be a direct effect of therapeutic LTG doses. LTG treatment seems inappropriate in SME.
EEG Background as Predictor of Electrographic Seizures in High‐Risk Neonates
Authors: Laroia Nirupama , Guillet Ronnie , Burchfiel James , McBride Margaret C.
Published: August 2005

Summary: Purpose: Experience with continuous EEG monitoring in 29 consecutive infants at risk of neonatal seizures demonstrated that background abnormalities on the initial EEG were strongly associated with electrographic seizures in the subsequent 18–24 h. To test this association prospectively, we examined the relationship between EEG background and the presence of electrographic seizures in the next 22 at‐risk infants monitored for seizures.

Methods: A standard EEG was recorded for each infant at risk for seizures. Based on specific criteria, the background was graded as normal; immature for age; or mildly, moderately, or severely abnormal. The EEG was then monitored continuously until no electrographic seizures were recorded for 18–24 h.

Results: Findings in the retrospective group of 29 infants and the prospective group of 22 infants did not differ. For the combined 51 infants, a normal or immature initial EEG background predicted the absence of seizures in the subsequent 18–24 h with a sensitivity of 96% [confidence interval (CI) 0.88, 1.01 and specificity of 81% (CI 0.67, 0.96). Administration of antiepileptic drugs (AEDs) before the start of the EEG recording did not affect this association.

Conclusions: In 51 consecutively monitored infants at risk for neonatal seizures, a normal or immature EEG background strongly predicted the absence of electrographic seizures in the subsequent 18–24 h; background abnormalities strongly predicted the occurrence of electrographic seizures concomitantly or in the subsequent 18–24 h of recording. Screening infants at risk for neonatal seizures with a routine EEG allows identification of infants at highest risk for seizures, thus conserving resources required for continuous EEG monitoring and facilitating early intervention for seizures.
Oral Health and Dental Treatment Needs in Nigerian Patients with Epilepsy
Authors: Ogunbodede E. O. , Adamolekun B. , Akintomide A. O.
Published: August 2005

Summary: Purpose: We determined the prevalence of oral disorders and the dental treatment needs of outpatients with epilepsy.

Methods: A questionnaire was administered to 56 consecutive patients (35 males, 21 females) presenting to an outpatient clinic. All patients underwent dental examinations. The clinical and diagnostic features of each patient's epilepsy were also obtained.

Results: The mean age (±SD) of the patients was 25.1 ± 12.1 years (range, 12–56 years). Of 9 patients receiving phenytoin (PHT) monotherapy, 3 (33.3%) had gingival hypertrophy; 15 of 18 (83.3%) patients receiving PHT in combination with phenobarbital (PB) manifested the disorder. Traumatized anterior teeth were found in 26 (46.4%) patients with the males significantly more affected than females (p = 0.02). When the dental treatment needs were considered, 24 (42.9%) patients required dental prophylaxis with oral hygiene instruction, and an equal number required various types of restorative treatments. Only 13 patients (23.2%) had previously visited a dental clinic; the 43 (76.8%) who had never sought dental treatment claimed they did not see any need for it.

Conclusions: Our study showed an increased predilection to anterior dental injuries in patients with epilepsy as compared with the prevalence earlier reported for those without epilepsy in Nigeria (p = 0.00). There is a clear need for effective interaction between medical and dental practitioners in the management of epilepsy.
Surgical Outcome in Patients with Epilepsy with Occult Vascular Malformations Treated with Lesionectomy
Authors: Abson Kraemer Diana L. , Griebel May L. , Lee Namsoo , Friedman Allan H. , Radtke Rodney A.
Published: August 2005

Summary: Purpose: This retrospective study reports the long‐term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure.

Methods: Fifteen patients with medically intractable epilepsy and angiographically occult vascular malformations (AOVMs) were treated surgically with lesionectomy at Duke University Medical Center. Lesionectomy consisted of removal of the AOVM and surrounding hemosiderin‐stained brain only, without the use of electrocorticography (ECoG) to guide resection.

Results: Eleven (73%) patients are seizure free after lesionectomy. Three showed no significant improvement, and one patient died, presumably after a seizure. Age of onset, duration of seizures, age at resection, and gender did not affect outcome. All patients with neocortical AOVMs in whom EEG findings correlated with the site of the lesion were seizure free after lesional resection. Treatment failures were associated with the presence of multiple intracranial lesions, poorly localized or diffuse EEG findings, discordant positron emission tomography (PET) imaging, or with a lesion in close proximity to the limbic system.

Conclusions: Lesionectomy, with removal of surrounding hemosiderin‐stained brain, can be considered the procedure of choice in carefully selected patients with epilepsy with occult vascular malformations.
Longitudinal Quantitative Hippocampal Magnetic Resonance Imaging Study of Adults with Newly Diagnosed Partial Seizures: One‐Year Follow‐Up Results
Authors: Van Paesschen W. , Duncan J. S. , Stevens J. M. , Connelly A.
Published: August 2005

Summary: Purpose: We wished to establish whether hippocampal changes occur in 1 year in adults with newly diagnosed partial seizures and, if so, to identify possible causes and mechanisms.

Methods: Thirty‐six adult patients with newly diagnosed partial seizures underwent a magnetic resonance imaging (MRI) scan of the brain including hippocampal volume and T, relaxation time (HCT2) measurement and had a follow‐up quantitative MRI scan ∼1 year after the baseline MRI scan.

Results: At baseline, 4 patients (11%) had hippocampal sclerosis (HS), 4 (11%) had abnormalities other than HS, and 28 had a normal MRI scan (78%). Twenty‐three patients (64%) had recurrent seizures in the period between the two MRI scans. One of the 4 patients with HS, who had daily seizures, had significantly increased HCT2 values on follow‐up, possibly reflecting progressive hippocampal damage. None of the 32 patients with MRI findings other than HS at baseline progressed to HS on follow‐up. However, 2 of the 32 patients had significant hippocampal changes, probably related to resolution of inflammatory swelling or edema after seizures were controlled.

Conclusions: Subtle changes in hippocampi can occur in 1 year in adults with newly diagnosed partial seizures, which could be due to resolution of edema after seizure control or to hippocampal changes associated with frequent and daily seizures. Follow‐up of the studied cohort for several years will be required to settle the question of whether progressive hippocampal damage occurs in temporal lobe epilepsy (TLE).
Fixation‐Off and Eyes Closed Catamenial Generalized Nonconvulsive Status Epilepticus with Eyelid Myoclonic Jerks
Authors: Ming Xue , Kaplan Peter W.
Published: August 2005

Summary: Purpose: Eyelid myoclonic jerks have been described in fixation‐off‐sensitive (FOS) epilepsy, but their relationship to nonconvulsive status epilepticus (NCSE) or to catamenial exacerbations is little reported.

Methods: We describe a woman of normal intelligence with catamenial periods of prolonged NCSE who exhibited various intra‐ and interseizure thresholds of polyspike suppression when her eyes were open, with particular visual inputs and with antiepileptic drug (AED) treatment.

Results: In one episode, on the first day of the woman's menstrual period, bursts of bilateral synchronous polyspike activity were briefly suppressed with visual fixation but were more lastingly suppressed after administration of lorazepam (LZP). During another period of NCSE, the SE was completely suppressed by visual fixation on objects and patterned checkerboard screens and by ocular convergence, was incompletely suppressed when her eyes were open in a dark room and when her eyes were open without visual fixation, but was not suppressed by mental activation alone.

Conclusions: FOS polyspike bursts with eyelid myoclonic jerks may exhibit catamenial exacerbations, varying from completely suppressible with visual fixation to nonsuppressible during NCSE. These findings suggest an interplay between humoral factors, AEDs, and seizure threshold in this condition.