bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Epilepsy with Unilateral and Bilateral Malformations of Cortical Development
Authors: Bartolomei Fabrice , Gavaret Martine , Dravet Charlotte , Guerrini Renzo
Published: August 2005

Summary: Purpose: To describe a family in whom two sisters with epilepsy, mental retardation, and microcephaly had different malformations of cortical development detected by magnetic resonance imaging (MRI).

Methods: Clinical investigation of the patients and their family. High‐resolution MRI, cognitive testing, and repeated EEG recording in both patients.

Results: In one patient, the malformation was bilateral and diffuse but much more pronounced in the parietal and occipital regions, with MRI characteristics indicating pachygyria‐polymicrogyria. In the other patient, the abnormality involved the right hemisphere, predominating around the perisylvian region, with MRI more clearly indicative of polymicrogyria. A brother also had severe epilepsy, diffuse EEG abnormalities, mental retardation, and microcephaly, but could not be studied neuroradiologically.

Conclusions: Lack of MRI studies in the parents and brother does not allow a precise hypothesis on the mode of transmission. However, findings from this family indicate that unilateral malformations of cortical development detected during investigations after seizure onset may be genetically based, suggesting that a single genetic abnormality could be responsible for bilateral or unilateral malformations.
Telephone Validation of the Quality of Life in Epilepsy Inventory‐89 (QOLIE‐89)
Authors: Leidy Nancy Kline , Elixhauser Anne , Rentz Anne M. , Beach Robert , Pellock John , Schachter Steven , Willian Mary Kay
Published: August 2005

Summary: Purpose: To assess the psychometric properties of the Quality of Life in Epilepsy Inventory‐89 (QOLIE‐89) administered via telephone and to compare these properties with data gathered through self‐administration.

Methods: A study of 139 patients with epilepsy was undertaken at three clinical sites in the United States. Patients participated in both telephone interview (T) and self‐administration (S). Order effect was controlled through randomization (T‐S and S‐T). Twenty‐eight S‐T subjects participated in an assessment of the 2‐week reproducibility of telephone interviews.

Results: Internal consistency and test‐retest reliability levels of the QOLIE‐89 overall score were very high across method of administration (T = 0.98; S = 0.98; ICC of T = 0.96). Scores were significantly related to mood (Profile of Mood States, r= ‐0.76, for both methods, p > 0.001) and two indicators of epilepsy severity (seizure frequency in the past month, T: r= 0.52, p > 0.0001; S: r= 0.54, p > 0.0001; days since last seizure, T: r= 0.28, p > 0.001; S: r= 0.25, p > 0.01), with no significant differences in coefficients by method of administration. Performance of the measure was consistent for patients with unimpaired and impaired memory, using the River‐mead Behavioural Memory Test, and across level of education.

Conclusions: Results of this study indicate telephone interview is a viable option for evaluating HRQL in persons with epilepsy and support the reliability and validity of the QOLIE‐89 regardless of method of administration.
Distribution of Epilepsy Syndromes in a Cohort of Children Prospectively Monitored from the Time of Their First Unprovoked Seizure
Authors: Shinnar Shlomo , O'Dell Christine , Berg Anne T.
Published: August 2005

Summary: Purpose: To assess the distribution of epilepsy syndromes and their stability in children.

Methods: A cohort of 407 children with a first unprovoked seizure was prospectively recruited and followed up for a mean of 9.4 years. Etiology and epilepsy syndromes were classified by using the International League Against Epilepsy (ILAE) guidelines in the 182 children with two or more seizures. Classification was done both at time of second seizure and at last follow‐up. Two‐year terminal remission also was analyzed by etiology and epilepsy syndrome.

Results: Etiology of epilepsy syndromes was idiopathic in 45 (25%), cryptogenic in 89 (49%), and remote symptomatic in 48 (26%). In the initial classification, 114 (63%) children had a localization‐based epilepsy syndrome including idiopathic in 26, cryptogenic in 34, and symptomatic based on localization or etiology in 54. Twenty‐one (12%) children had a generalized epilepsy syndrome, including 19 with primary generalized epilepsy. Forty‐seven (26%) cases were in the category of undetermined if focal or generalized. At last follow‐up, there was a change in either etiology (n = 16) or the final epilepsy syndrome classification (n = 33) or both (n = 15) in 34 (19%) cases. At time of last follow‐up, 144 (79%) of the children with epilepsy were in 2‐year terminal remission, and 108 (59%) were in 2‐year terminal remission without medications. Factors associated with a favorable prognosis included an idiopathic or cryptogenic etiology and having a localization‐based idiopathic epilepsy syndrome.

Conclusions: After two seizures, childhood‐onset epilepsy can be classified by etiology and epilepsy syndrome. Prognosis is favorable in the majority of cases. However, the apparent syndrome may change with longer follow‐up. The ability to classify these cases early in the clinical course is important if they are to be used for prognostic purposes.
Partial and Generalized Seizures Affect Reproductive Physiology Differentially in the Male Rat
Authors: Edwards Heather E. , Burnham W. McIntyre , MacLusky Neil J.
Published: August 2005

Summary: Purpose: Reproductive dysfunction and endocrine disorders occur frequently among men with epilepsy. This study tested the hypothesis that focal limbic seizures and generalized seizures may both contribute to reproductive dysfunction.

Methods: The rat kindling model was used to mimic focal limbic seizures. Kindling electrodes were placed in the basolateral amygdala. Male rats were either intact, gonadectomized (GDX) or GDX + testosterone (T) replaced and then kindled. Controls were left intact and sham‐kindled. Maximal electro‐convulsive shock (MES) treatment was used to model generalized seizures, by using eight stimulations, one every other day, for 2.5 weeks. Animals were killed either 3 h or 6 weeks after MES treatment to determine short‐ and long‐term effects.

Results: Kindled seizures resulted in an increase in serum testosterone, estradiol, and prolactin in intact males, accompanied by a significant increase in testis, epididymis, and pituitary weight, as well as a significant decrease in prostate weight. MES treatment caused a short‐term reduction in serum testosterone and testis, epididymis, and prostate weight. All parameters were restored to control values within 6 weeks of the last MES seizure, with the exception of pituitary weight and serum prolactin, which remained significantly elevated 6 weeks after MES treatment.

Conclusions: Our results indicate that both focal limbic (amygdaloid) seizures and generalized MES seizures disturb normal reproductive physiology in the male rat. Amygdaloid‐kindled seizures have mixed effects on different parameters of reproductive function, whereas MES seizures induce a transient hypogonadal state. These results suggest that reproductive dysfunction in men with epilepsy may result from seizure‐related interference with the normal functions of the hypothalamic‐pituitary‐testicular axis.
Modulation of Sodium Currents in Rat CA1 Neurons by Carbamazepine and Valproate After Kindling Epileptogenesis
Authors: Vreugdenhil Martin , Wadman Wytse J.
Published: August 2005

Summary: Purpose: To determine the modulation of sodium currents in hippocampal CA1 neurons by carbamazepine (CBZ) and valproate (VPA), before and after kindling epileptogenesis.

Methods: Voltage‐dependent sodium current was measured in isolated hippocampal CA1 neurons, by using the whole‐cell voltage‐clamp technique. CBZ (15–100 μM) or VPA (0.5‐5 mM) was applied by bath perfusion. Cells from fully kindled rats were compared with controls, 1 day and 5 weeks after the tenth generalized seizure.

Results: CBZ did not affect sodium current activation but selectively shifted the voltage dependence of steady‐state inactivation to more hyperpolarized potentials. One day after the last kindled generalized seizure, the shift induced by 15 μM CBZ was 2.1 ± 0.5 mV (mean ± SEM; n = 20) compared with 4.3 ± 0.3 mV (n = 16; p > 0.001) in matched controls. The EC50 of the concentration‐effect relation was 57 ± 6 μM compared with 34 ± 2 μM (p > 0.01) in controls. Five weeks after kindling, these values had recovered to a level not different from control. VPA induces at a relatively high concentration a similar but smaller shift in voltage dependence of inactivation than does CBZ. After kindling, the shift induced by 2 mM VPA (2.8 ± 0.6 mV; n = 19) was not different from controls (3.0 ± 0.5 mV; n = 22). The EC50 for VPA was 2.6 ± 0.3 mM compared with 2.5 ± 0.4 mM in controls.

Conclusions: Both CBZ and VPA selectively modulate the voltage dependence of sodium current steady‐state inactivation and as a consequence reduce cellular excitability. The effect of CBZ was reduced immediately after kindling epileptogenesis, apparently by a reduced affinity of its receptor. In contrast, the shift induced by VPA was not different at any stage after kindling epileptogenesis. The change in CBZ sensitivity after kindling is related to epileptic activity rather than to the epileptic state, because it almost completely recovers in a period without seizures.
Paradoxic Reaction to Lamotrigine in a Child with Benign Focal Epilepsy of Childhood with Centrotemporal Spikes
Authors: Catania Santiago , Cross Helen , Sousa Carlos de , Boyd Stewart
Published: August 2005

Summary: A girl aged 5 years developed nocturnal seizures (mouth twitching, salivation, anarthria, with right arm jerking and occasional secondary generalisation), with frequent focal sharp waves over the left centrotemporal region in her EEG, suggesting benign childhood epilepsy with centrotemporal spikes (BECTS). Seizures became diurnal and frequent, not modified by carbamazepine (CBZ) or valproate (VPA) but responding to VPA and lamotrigine (LTG) with recommended dosage schedules for this combination.

Her school performance then deteriorated insidiously, with poor memory and concentration, clumsiness, stuttering, and emotional lability. After 4 months, new episodes, ≥10 per day, occurred. These lasted a few seconds; she stared into space, her jaw dropped, her head dropped to the right, and her eyelids flickered. She usually maintained awareness. Attacks were often provoked by blowing or sneezing. Ictal EEG showed anterior‐predominant 3/s sharp‐slow wave complexes lasting ≥8 s, with bilateral rolandic discharges interictally. Withdrawal of LTG resulted in rapid improvement in cognitive function and gradual remission of the new attacks.

Conclusions: This appears to be a paradoxic reaction to LTG in the setting of BECTS.
Phenytoin Penetration into Brain After Administration of Phenytoin or Fosphenytoin
Authors: Walton Nancy Y. , Uthman Basim M. , El Yafi Karim , Kim Jae Moon , Treiman David M.
Published: August 2005

Summary: Purpose: This study was designed to measure the brain penetration of phenytoin (PHT) after intravenous (i.v.) administration of either standard PHT or fosphenytoin (FPHT), a PHT prodrug. The study was formulated to answer the question whether the time required for FPHT to be converted to PHT in the bloodstream would delay the accumulation of PHT in brain.

Methods: Four rats were sampled at various times after intravenous infusion of 30 mg/kg PHT i.v. or 30 mg/kg PHT equivalents of FPHT i.v. PHT was measured in serum, protein‐free ultrafiltrate, and in brain, by using high‐performance liquid chromatography.

Results: Although the initial PHT‐free fraction was significantly higher for FPHT‐treated rats than it was for PHT‐treated rats, brain PHT levels were significantly reduced after infusion of FPHT.

Conclusions: When FPHT is used for treatment of generalized status epilepticus, it should be anticipated that lower initial brain PHT levels will be achieved than are typically found with standard PHT.
Male Monozygotic Twins Discordant for Periventricular Nodular Heterotopia and Epilepsy
Authors: Sisodiya S. M. , Marques W. , Everitt A. , Sander J. W. A.
Published: August 2005

Summary: Purpose: To determine zygosity and study cerebral structure in apparently identical twins with discordant manifestation of focal epilepsy.

Methods: Male twins in their fifth decade were scanned by using magnetic resonance imaging (MRI) to detect structural abnormalities. Zygosity was determined by using 10 microsat‐ellite markers.

Results: DNA analysis showed that the twins were >99.99% likely to be monozygous; they were discordant for bilateral symmetric periventricular nodular heterotopia (PNH) and epilepsy.

Conclusions: The discordant occurrence of PNH and epilepsy in monozygotic male twins carries implications with respect to somatic mosaicism, currently held to be responsible for PNH in affected male subjects.
Do Reactive Post‐Resection “Injury” Spikes Exist?
Authors: Schwartz Theodore H. , Bazil Carl W. , Forgione Mennato , Bruce Jeffrey N. , Goodman Robert R.
Published: August 2005

Summary: Purpose: New post‐resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post‐resection injury spikes by eliminating the possibility of residual epileptogenic tissue.

Methods: Preresection and post‐resection ECoG was performed on seven patients with an intra‐axial neocortical tumor (glioblastoma multiforme or metastasis) and no history of seizures. All tumors were gross‐totally resected.

Results: The mean age of the patients was 59 years. The tumor location was frontal in four patients, parietal in two, and temporal in one. Two patients had preresection spikes with an average rate of 68 spikes/min that disappeared after surgery. Two different patients had new post‐resection spikes, with an average firing rate of 4 spikes/min, despite normal preresection ECoG. In one of these patients, the new spikes were superimposed over a burst suppression pattern. Neither patient developed seizures after surgery.

Conclusions: Surgical irritation of the neocortex is sufficient to produce reactive post‐resection epileptogenic discharges surrounding an intra‐axial neocortical tumor even in the absence of preoperative seizures and spikes. Injury spikes fire at a slow rate and are not predictive of clinical seizures.
Postictal Central Apnea as a Cause of SUDEP: Evidence From Near‐SUDEP Incident
Authors: So Elson L. , Sam Maria C. , Lagerlund Terrence L.
Published: August 2005

Summary: While undergoing video‐EEG monitoring, a 20‐year‐old woman had a 56‐second convulsive seizure, after which she developed persistent apnea. The rhythm of the electrocardiogram complexes was unimpaired for approximately 10 seconds, after which it gradually and progressively slowed until it stopped 57 seconds later. Evaluation after successful cardiorespiratory resuscitation showed no evidence of airway obstruction or pulmonary edema. The patient had a previous cardio‐respiratory arrest after a complex partial seizure without secondary generalization. Although epileptic seizures are known to be potentially arrhythmogenic to the heart, our observations strongly suggest that one probable mechanism of sudden unexplained death in epilepsy is the marked central suppression of respiratory activity after seizures.
A Multicenter Randomized Controlled Trial on the Clinical Impact of Therapeutic Drug Monitoring in Patients with Newly Diagnosed Epilepsy
Authors: Jannuzzi G. , Cian P. , Fattore C. , Gatti G. , Bartoli A. , Monaco F. , Perucca E. ,   The Italian TDM Study Group in Epilepsy
Published: August 2005

Summary: Purpose: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.

Methods: One‐hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel‐group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10–20 μg/ml for PHT, 15–40 μg/ml for PB, 4–11 μg/ml for CBZ, and 40–100 μg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.

Results: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2‐year follow‐up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p ≤0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12‐month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12‐month remission. Frequency of adverse effects was almost identical in the two groups.

Conclusions: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome, and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.
Chemical Shift Imaging Spectroscopy and Memory Function in Temporal Lobe Epilepsy
Authors: Pauli E. , Eberhardt K. W. E. , Schäfer I. , Tomandl B. , Huk W. J. , Stefan H.
Published: August 2005

Summary: Purpose: Hippocampal neuron loss and associated memory deficits are characteristic of intractable temporal lobe epilepsy (TLE). Proton chemical shift imaging (CSI) spectroscopy is a sensitive tool for detecting neuronal loss. The aim of this study was to investigate the correlation between memory functions and results provided by CSI spectroscopy of the hip‐pocampal structures.

Methods: Ten patients with cryptogenic TLE participated. The study protocol involved both the acquisition of high‐spatial‐resolution CSI spectroscopy and neuropsychological evaluation, including memory testing and intracarotid sodium amytal test (IAT). The analysis of the CSI data was based on normative data obtained in 30 healthy volunteers. Memory functions were represented by verbal, visual, and general memory indices.

Results: A significant correlation was found between CSI spectroscopy of the hippocampal formation and the verbal memory indices for the dominant hemisphere. In addition, there was a significant correspondence of the qualitative judgment “hippocampal pathology indicated by CSI spectroscopy” and both “material specific memory deficit” and “memory deficits in the IAT.”

Conclusions: Our results demonstrate that CSI spectroscopy of the hippocampal structures is strongly related to lateralized memory deficits in patients with TLE. This suggests that CSI spectroscopy may be useful in the prediction of postoperative outcome in respect of seizure control and memory.
Reduction of Epileptiform Activity in Response to Low‐Dose Clonazepam in Children with Epilepsy: A Randomized Double‐Blind Study
Authors: Dahlin Maria , Knutsson Evert , Åmark Per , Nergårdh Arne
Published: August 2005

Summary: Purpose: To evaluate the effect of low‐dose clonazepam (CZP) on the amount of epileptiform activity in children with focal and generalized epilepsy.

Methods: In a single‐blind pilot study, followed by a double‐blind, placebo‐controlled, randomized, crossover study, 15 children with epilepsy were evaluated by using 24‐h long‐term EEG recordings during baseline days and days after injections of placebo and CZP. The drug was given as a single i.m. injection of 0.02 mg/kg BW. Blood samples were obtained regularly for analysis of plasma concentrations of CZP. The number of epileptiform discharges was determined during corresponding periods with the individual child in the same state of alertness, the same real time of day, and with concomitant antiepileptic drugs (AEDs) unchanged.

Results: In the double‐blind study, low‐dose CZP produced a highly significant (p = 0.0015) decrease in the amount of epileptiform activity (mean, ‐69% vs. placebo, ‐2%) obtained during periods when median plasma concentrations ranged from 18 to <14 nM. The maximal plasma level (median, 24 nM) was reached before the start of the analysis periods. The pilot study showed reductions of epileptiform discharges within the same range as the double‐blind study. In the children with daily seizures, a parallel decrease in seizures and the number of epileptiform discharges was seen after the administration of CZP.

Conclusions: Our data demonstrate a significant reduction of epileptiform discharges on long‐term EEGs after a single low dose of CZP with concomitant low plasma levels, which were considerably lower than the doses and plasma levels usually recommended. A concomitant reduction of seizures also was seen.
Improved Prediction of Nonepileptic Seizures with Combined MMPI and EEG Measures
Authors: Storzbach D. , Binder L. M. , Salinsky M. C. , Campbell B. R. , Mueller R. M.
Published: August 2005

Summary: Purpose: Nonepileptic seizures (NESs) are frequently mistaken for epileptic seizures (ESs). Improved detection of patients with NESs could lead to more appropriate treatment and medical cost savings. Previous studies have shown the MMPI/MMPI‐2 to be a useful predictor of NES. We hypothesized that combining the MMPI‐2 with a physiologic predictor of epilepsy (routine EEG; rEEG) would result in enhanced prediction of NES.

Methods: Consecutive patients undergoing CCTV‐EEG monitoring underwent rEEG evaluation and completed an MMPI‐2. Patients were subsequently classified as having epilepsy (n = 91) or NESs (n = 76) by using standardized criteria. Logistic regression was used to predict seizure type classification.

Results: Overall classification accuracy was 74% for rEEG, 71% for MMPI‐2 Hs scale, and 77% for MMPI‐2 Hy scale. The model that best predicted diagnosis included rEEG, MMPI‐2, and number of years since the first spell, resulting in an overall classification accuracy of 86%.

Conclusions: The high accuracy achieved by the model suggests that it may be useful for screening candidates for diagnostic telemetry.
Neuropsychological Functions in Idiopathic Occipital Lobe Epilepsy
Authors: Gülgönen Sibel , Demirbilek Veysi , Korkmaz Bariş , Dervent Ayşm , Townes Brenda D.
Published: August 2005

Summary: Purpose: Despite the benign prognoses of idiopathic partial epilepsies, particularly regarding the response of seizures to treatment, some evidence now exists that patients with such disorders may have subtle neuropsychological deficits. This study was designed to investigate several modalities of neuropsychological functioning in a group of 21 patients, ranging from 6 to 14 years of age, with idiopathic occipital lobe epilepsy (IOLE). The case patients were compared with 21 healthy controls matched for age, sex, and socioeconomic status.

Methods: A battery of age‐appropriate neuropsychological tests was administered individually to all the participants. Tests were chosen on the basis of age‐appropriate norms, their ability to represent a wide variety of functional domains, and their appropriateness in a cross‐cultural setting. The tests were selected to measure functioning in six domains: intellectual functioning, attention, memory, academic achievement, visual‐motor functioning, and executive functioning; some were further subdivided by their verbal‐versus‐visual modality of functioning.

Results: The results revealed no significant difference in basic neurophysiological functions between the patient and control groups, although the case patients' performance scores were lower in attention (p <0.01) and memory (p <0.01), as well as in intellectual functioning (p <.05).

Conclusions: The possibility of subtle cognitive deficits in IOLE patients should always be considered, though further studies are necessary to elaborate their precise and long‐term effects.
Antiepileptic Therapies in the Mifi Province in Cameroon
Authors: Preux P.‐M. , Tiemagni F. , Fodzo L. , Kandem P. , Ngouafong P. , Ndonko F. , Macharia W. , Dongmo L. , Dumas M.
Published: August 2005

Summary: Purpose: To evaluate the availability and accessibility of antiepileptic drugs (AEDs) in two health districts in Cameroon.

Methods: The study included 33 patients with epilepsy, 26 physicians, 13 private pharmacists, eight hospital pharmacists, three distributors, and eight traditional healers. Structured questionnaires were used to assess the knowledge of the disease, treatment accessibility, the methods of prescriptions, and the availability and the frequency of delivery of drugs.

Results: Only one of 33 patients did not take modern treatment; 91% of the patients were followed up by a traditional healer, and 78%, by an hospital physician. Phenobarbitone (PB) was the most frequently prescribed drug by 69% of the doctors; 54% of the physicians considered the traditional therapies to be incompatible with modern drug treatment. By pharmacists, PB was delivered regularly. Other drugs went out of stock frequently. The number of packages in stock varied significantly directly with the frequency of delivery. The mean price per package and the mean number of packages in stock were higher in the public hospital pharmacies than in the private pharmacies. A majority of healers explained epilepsy as the presence of excess foam in the abdomen. The remedies proposed were to stop foam secretion.

Conclusions: Availability of AEDs was quite high, but with no strict correspondence between the rate of prescriptions and the supply of the drugs.
Clinical Relevance of Quantified Intracranial Interictal Spike Activity in Presurgical Evaluation of Epilepsy
Authors: Hufnagel A. , Dümpelmann M. , Zentner J. , Schijns O. , Elger C. E.
Published: August 2005

Summary: Purpose: Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone.

Methods: We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site.

Results: The following results were obtained: (a) Within a zone ≤2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters.

Conclusions: The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.
Myoclonus Associated with the Use of Gabapentin
Authors: Asconapé Jorge , Diedrich Andrea , DellaBadia John
Published: August 2005

Summary: Purpose: To report on the occurrence of myoclonus in patients receiving gabapentin (GBP) for the treatment of epilepsy.

Methods: Clinic charts of 104 consecutive patients started on GBP were reviewed. All patients were treated by the same physician, and most were specifically asked about the presence of myoclonus.

Results: We found 13 cases of myoclonus. All patients had refractory epilepsy and were taking other antiepileptic drugs (AEDs). Six patients had a severe chronic static encephalopathy; five patients had no medical diagnosis other than seizures. Ten patients developed multifocal myoclonus. Three patients developed focal myoclonus, contralateral to their epileptic focus. Two patients had an exacerbation of preexistent myoclonus. An EEG performed during myoclonus on three patients showed no correlate. The myoclonus tended to persist as long as GBP was maintained, whereas discontinuance of GBP resulted in rapid cessation of the myoclonus. In all cases the myoclonus was subtle and did not significantly interfere with daily activities.

Conclusions: GBP‐associated myoclonus appears to be relatively frequent. It is usually mild and can easily be overlooked. Discontinuation of therapy is not necessary in most cases.
Distribution and Initiation of Seizure Activity in a Rat Brain with Subcortical Band Heterotopia
Authors: Chen Zong‐Fu , Schottler Frank , Bertram Edward , Gall Christine M. , Anzivino Matthew J. , Lee Kevin S.
Published: August 2005

Summary: Purpose: Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies. To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure‐prone mutant rat (tish) exhibiting subcortical band heterotopia.

Methods: Depth electrode recordings and postmortem assessment of regional c‐fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo. Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4‐aminopyridine).

Results: Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex. Spontaneous seizures induce c‐fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions. The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices. Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex.

Conclusions: These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat. Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons. The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex.
Estradiol Facilitates Kainic Acid—Induced, but not Flurothyl‐Induced, Behavioral Seizure Activity in Adult Female Rats
Authors: Woolley Catherine S.
Published: August 2005

Summary: Purpose: This study was designed to determine whether previously demonstrated increases in hippocampal axospinous synapse density and NMDA receptor function induced by estradiol are paralleled by increased susceptibility to limbic (kainic acid induced) or generalized (flurothyl induced) behavioral seizures.

Methods: Kainic acid was injected systemically to ovariectomized adult female rats treated with either estradiol or oil vehicle. The latencies to each of five stages of seizure‐related behaviors (staring, wet‐dog shakes, head waving and chewing, forelimb clonus, rearing, and falling) were recorded for each animal. Flurothyl was administered by inhalation to ovariectomized adult female rats treated with estradiol alone, estradiol followed by short‐term progesterone, or oil vehicle. The latencies to each of three stages of seizure‐related behaviors (first myoclonic jerk, forelimb clonus, wild running and bouncing) were recorded for each animal.

Results: Estradiol treatment decreased the latency to seizure‐related behaviors induced by kainic acid, but neither estradiol alone nor estradiol followed by progesterone had any effect on flurothyl‐induced seizure‐related behaviors.

Conclusions: The same estradiol treatment paradigm known to induce structural and functional changes in the excitatory circuitry of the hippocampus facilitates the progression of kainic acid‐induced seizures, which are known to involve the hippocampus, but has no effect on flurothyl‐induced seizures. The lack of an effect of estradiol alone or estradiol followed by progesterone on flurothyl‐induced seizures indicates that estradiol's effects on seizure susceptibility do not result from increased neuronal excitability throughout the brain, but rather involve action within the limbic system. The data suggest that structural and functional changes in hippocampal circuitry induced by estradiol may contribute to increased susceptibility to limbic seizure activity.
Epilepsy, Vagal Nerve Stimulation by the NCP System, All‐Cause Mortality, and Sudden, Unexpected, Unexplained Death
Authors: Annegers J. F. , Coan Sharon P. , Hauser W. A. , Leestma J.
Published: August 2005

Summary: Purpose: This report concerns the 2‐year extension of the study of mortality and sudden, unexpected, unexplained death in epilepsy (SUDEP) in the cohort of patients receiving vagal nerve stimulation by the NCP System for the treatment of epilepsy.

Methods: A cohort of 1,819 individuals was followed 3,176.3 person‐years from implantation. The 25 deaths that occurred during NCP System activation were reviewed for SUDEP by a panel.

Results: The mortality rates were lower [standardized mortality ratio (SMR = 3.6)] with the extended follow‐up compared to the previous finding (SMR = 5.3). The SUDEP rates (4.1 vs. 4.5 per 1,000 person‐years) were similar to those in the previous study of this cohort. When the vagal nerve stimulation experience is stratified by duration of use, the rate of SUDEP was 5.5 per 1,000 over the first 2 years, but only 1.7 per 1,000 thereafter.

Conclusions: The mortality and SUDEP rates are similar to those reported from clinical trials of new drugs and cohorts of severe epilepsy. The lower SUDEP rates after 2 years of follow‐up are intriguing, but require further investigation.
Early Recognition of Benign Partial Epilepsy in Infancy
Authors: Okumura Akihisa , Hayakawa Fumio , Kato Toru , Kuno Kuniyoshi , Negoro Tamiko , Watanabe Kazuyoshi
Published: August 2005

Summary: Purpose: The aim of this study is to determine how precisely we can recognize the outcome in infants with epilepsy beginning in the first year of life.

Methods: We performed a prospective 5‐year follow‐up study on 63 patients who developed epilepsy in the first year of life. We first judged that patients met the criteria of “possible benign partial epilepsy in infancy (BPEI)” on enrollment in this study. At 2 years of age, we reevaluated the seizure and developmental outcome in the patients who were diagnosed as having “possible BPEI.” We finally judged that patients met the criteria of “definite BPEI” at age 5 years. “Possible BPEI” was defined as epilepsy meeting all the following conditions: (a) complex partial seizures and/or secondarily generalized seizures; (b) normal psychomotor development and neurologic findings before onset; (c) normal interictal electroencephalograms; (d) normal cranial computed tomography (CT) and magnetic resonance imaging (MRI) findings; and (e) no seizures during the first 4 weeks of life. “Definite BPEI” was defined as epilepsy meeting all the following criteria in addition to those of “possible BPEI”: (a) normal psychomotor development beyond age 5 years, and (b) no seizures beyond age 2 years.

Results: Thirty‐two of the 63 patients met the inclusion criteria completely and were included in the “possible BPEI” group. Twenty‐five of the 32 patients completed the 5‐year follow‐up. At age 2 years, four patients were excluded from the “possible BPEI” group because of seizure recurrence and/or delayed development. By age 5 years, one had a recurrence of seizures, and another exhibited mildly delayed psychomotor development. We finally diagnosed 19 patients as having “definite BPEI.”“Definite BPEI” accounted for 76% of the patients diagnosed as having “possible BPEI” at the first presentation and 90% of those who met the conditions on reevaluation at age 2 years.

Conclusions: Recognition of BPEI is possible, to some extent, at the first presentation, and reevaluation at age 2 years is useful for a more precise diagnosis.
Referral Characteristics of Primary Care Physicians for Seizure Patients
Authors: Moore J. Layne , McAuley James W. , Mott David , Reeves Andrew L. , Bussa Barbara
Published: August 2005

Summary: Purpose: To investigate primary care physicians' behavior with respect to referral patterns, antiepileptic drug (AED) initiation, and level of comfort in managing seizure patients.

Methods: A cross‐sectional descriptive study design was used for collecting and analyzing data. A 20‐item survey was developed and mailed to 8,195 primary care physicians including family practitioners, internal medicine physicians, and obstetrics–gynecologists throughout the state of Ohio; 504 primary care physicians that interact regularly with epilepsy patients responded to the survey.

Results: Two patterns of referral emerged. Data showed that the majority (n = 382) of physicians refer 50% of their patients, but a minority of physicians (n = 122) refer <50% of their patients. Differences between the two groups existed in three of the four research questions asked: who initiates AED therapy, comfort level, and percentage of patients referred to a neurologist. Influence of managed care on decision making was not different between the two groups.

Conclusions: A minority of primary care physicians rate themselves very comfortable with seizure patients. These same physicians refer a minority of their patients to a neurologist. As a whole, however, primary care physicians refer a majority of their seizure patients to a neurologist. Neurologists evaluate most seizure patients because most primary care physicians claim not to be extremely comfortable with evaluation and treatment of seizures. We conclude that neurologists play an essential role in the treatment of most seizure patients.
Validation of a New Quality of Life Measure for Children with Epilepsy
Authors: Sabaz Mark , Cairns David R. , Lawson John A. , Nheu Natalina , Bleasel Andrew F. , Bye Ann M.E.
Published: August 2005

Summary: Purpose: There is no adequate measure of health‐related quality of life (HRQOL) specifically for children with epilepsy. The aim of this study was to develop an epilepsy‐specific HRQOL questionnaire for children, covering five domains: physical function, emotional well‐being, cognitive function, social function, and behavior. Second, we aimed to demonstrate the instrument's reliability and validity, and its sensitivity to differences in epilepsy severity.

Methods: The subjects were guardians of children with refractory epilepsy, whose syndrome had been defined by using video‐EEG monitoring. Each family completed the developed epilepsy‐specific HRQOL scale for children and two standard, generic measures of HRQOL.

Results: The results indicated that each of the scales of the questionnaire had good internal consistency reliability. Furthermore, each scale correlated more highly with theoretically similar scales on established, generic health measures than with theoretically dissimilar scales (construct validity). The sensitivity of the questionnaire to differences in epilepsy severity also was demonstrated. As seizure severity increased, HRQOL subscale scores decreased, independent of age, gender, age of seizure onset, and IQ. Further, there was a negative relation between the number of antiepileptic medications taken and measures of memory and language performance, which was independent of age, gender, age of seizure onset, IQ, and seizure severity.

Conclusions: This study demonstrated that the developed HRQOL instrument is a reliable and valid measure and is sensitive to differences in epilepsy. These results indicate that this new instrument may be a viable medical or surgical outcome measure for children with epilepsy.
Intractable Seizures of Frontal Lobe Origin: Clinical Characteristics, Localizing Signs, and Results of Surgery
Authors: Jobst B. C. , Siegel A. M. , Thadani V. M. , Roberts D. W. , Rhodes H. C. , Williamson P. D.
Published: August 2005

Summary: Purpose: We analyzed the clinical characteristics of seizures of frontal lobe (FL) origin with particular emphasis on establishing different categories and determining if these categories had any localizing or lateralizing value. In addition, results of surgery are reported.

Methods: Seizure characteristics were established by historical review and electroencephalographic/videotape analysis of 449 seizures in 26 adult patients with refractory seizures of FL origin.

Results: No outstanding risk factor was identified for seizures of FL origin. Seizures were frequent (7.1 per week), brief (mean duration, 48.3 seconds), and had a nocturnal preponderance in 58% of the patients. Status epilepticus was reported in 54%, and generalized convulsions as a prominent seizure type were reported in 26% of patients. The most common reported aura was a nonspecific sensation, often localized to the head (35%). Early forced head and eye deviation was not a consistent lateralizing sign, whereas late head and eye deviation always occurred contralateral to the site of seizure origin. Early asymmetric tonic posturing occurred consistently contralateral to the side of seizure origin. Clinical seizure patterns did not consistently localize to specific regions of the frontal lobe, although there were some noticeable trends: focal clonic seizures were associated with seizure origin in the frontal convexity; tonic seizures were most often associated with origin in the supplementary motor area but also occurred with origin in other parts of the frontal lobe; seizures resembling typical temporal lobe seizures with oroalimentary automatisms were observed with seizure origin in the orbitofrontal region; and seizures with hyperactive, frenetic automatisms were not associated with any specific region within the frontal lobes. Eighty percent of patients had favorable seizure outcome after surgery (class I/II).

Conclusion: Although certain clinical features are characteristic for seizures of frontal lobe origin and some have lateralizing value, they do not localize to specific areas within the FL. After careful presurgical evaluation, both lesional and non‐lesional patients benefit from epilepsy surgery.
A Double‐Blind, Placebo‐Controlled Study of Topiramate in Adult Patients with Refractory Partial Epilepsy
Authors: Yen Der‐Jen , Yu Hsiang‐Yu , Guo Yuh‐Cherng , Chen Chien , Yiu Chun‐Hing , Su Ming‐Shung
Published: August 2005

Summary: Purpose: The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double‐blind, placebo‐controlled study.

Methods: A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8‐week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placcbo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial.

Results: In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a 50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group.

Conclusions: TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.
A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures
Authors: Aldenkamp A. P. , Baker G. , Mulder O. G. , Chadwick D. , Cooper P. , Doelman J. , Duncan R. , Gassmann‐Mayer C. , de Haan G. J. , Hughson C. , Hulsman J. , Overweg J. , Pledger G. , Rentmeester T. W. , Riaz H. , Wroe S.
Published: August 2005

Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil‐ity and prevents cognitive impairment.

Methods: The study is a multicenter, randomized, observer‐blinded, parallel‐group clinical trial with VPA or TPM given as first‐line add‐on therapy to steady‐state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25‐mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach.

Results: For the 10 baseline‐to‐end point comparisons, one test measuring short‐term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline‐to‐titration comparisons also show one statistically significant difference, again for a test measuring short‐term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration.

Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).