bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral Posterior Parietal Polymicrogyria: A Mild Form of Congenital Bilateral Perisylvian Syndrome?
Authors: Montenegro Maria Augusta , Guerreiro Marilisa M. , Lopes‐Cendes Iscia , Cendes Fernando
Published: March 2003

Summary:  Purpose: The main features of congenital bilateral perisylvian syndrome (CBPS) are pseudobulbar palsy, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies, however, the clinical spectrum of this syndrome is much wider than previously believed and may vary from minor speech difficulties to severely disabled patients. The objective of this study was to present the different imaging and clinical findings of 17 patients with CBPS, their genetic background, and the occurrence of prenatal injury during their pregnancies.

Methods: We evaluated 17 consecutive patients with CBPS and divided them into two groups according to the imaging findings: (a) diffuse polymicrogyria around the sylvian fissure and (b) posterior polymicrogyria at the posterior parietal regions. They were systematically interviewed regarding history of prenatal events during their pregnancies, family history of speech difficulties, epilepsy, or other neurologic abnormality.

Results: There were seven women, ages ranging from 3 to 41 years (mean, 11.5; median, 7 years). Seven patients had bilateral posterior parietal polymicrogyria (BPPP), and 10 had diffuse bilateral perisylvian polymicrogyria. All seven patients with BPPP had only minor speech difficulties, none had epilepsy, and all but one had a family history of epilepsy or cortical dysgenesis. In contrast, 10 patients with diffuse bilateral perisylvian polymicrogyria had pseudobulbar palsy, four had epilepsy, eight had a history of a major prenatal event, and only four had a family history of epilepsy or developmental delay.

Conclusions: These findings suggest that diffuse bilateral perisylvian polymicrogyria appears to be more related to injuries caused by environmental factors, whereas BPPP has a stronger genetic predisposition. In addition, BPPP appears to have a wider clinical spectrum than previously believed, and may represent a milder extreme within the spectrum of CBPS.
A Study of the Effect of Color Photostimulation from a Cathode‐ray Tube (CRT) Display on Photosensitive Patients: The Effect of Alternating Red–Cyan Flicker Stimulation
Authors: Shirakawa Seigo , Funatsuka Makoto , Osawa Makiko , Fujita Michinari , Oguni Hirokazu
Published: March 2003

Summary:  Purpose: In an attempt to establish evidence for developing better guidelines for the production of animation programs that would not induce photosensitive seizures in Japan, we evaluated the effects of red flicker, alternating red/cyan (complementary color to red) flicker stimuli, and of contrast between the red and cyan frames from a cathode‐ray tube (CRT) display in photosensitive patients.

Methods: We studied 35 photosensitive patients. They were exposed to seven types of flicker. The first three types were alternating red/cyan flicker (R/C) with the luminance of cyan set at three different levels, high, equal, and low luminance (65, 20, and 16 cd/m2, respectively) relative to the red (20 cd/m2). The following four types were red, cyan, yellow, and magenta flicker stimuli. EEGs were recorded while the patients watched these stimuli on a CRT display.

Results: Rates of photoparoxysmal response (PPR) provocation were 11.4, 13.7, and 14.0% with high‐, no‐ and low‐contrast R/C flicker, respectively, and 3.7% with red flicker. The differences between red and each of the other R/C flicker stimuli were all statistically significant (p<0.05, 0.01, 0.01). No significant differences were found between the effects by each of the three levels of contrast in alternating R/C flicker (p > 0.05).

Conclusions: These findings suggest that alternating R/C flicker is more provocative than simple red flicker, and that contrast between frames of different colors may play some role in the effects of alternating flicker stimuli from a CRT display in photosensitive patients. Therefore, caution against the use of the combination of red and cyan, in addition to the red flicker stimulus, should be included in any guidelines drawn up to prevent photosensitive seizures.
Vagus Nerve Stimulation for the Treatment of Bilateral Independent Temporal Lobe Epilepsy
Authors: Alsaadi Taoufik M. , Laxer Kenneth D. , Barbaro Nicholas M. , Marks William J. , Garcia Paul A.
Published: March 2003

Summary:  Purpose: We studied the effect of vagus nerve stimulation (VNS) on seizure reduction in patients with intractable epilepsy with bilateral independent temporal lobe foci.

Methods: Ten patients who met the criterion of the presence of two distinctive clinical and ictal EEG seizure patterns were identified and followed up for 1 year.

Results: Six patients had >50% reduction in their seizure frequency that persisted up to ≥1 year of follow‐up, whereas four patients reported small or no reduction in their partial seizures.

Conclusions: VNS is often effective and well tolerated in this select group of intractable epilepsy patients.
Involvement of the Thalamocortical System in Epileptic Loss of Consciousness
Authors: Kostopoulos George K.
Published: March 2003

Summary:Experiments on putative neuronal mechanisms underlying absence seizures as well as clinical observations are critically reviewed for their ability to explain apparent “loss of consciousness.” It is argued that the initial defect in absences lies with corticothalamic (CT) neuronal mechanisms responsible for selective attention and/or planning for action, rather than with those establishing either the states or the contents of consciousness. Normally, rich thalamocortical (TC)–CT feedback loops regulate the flow of information to the cortex and help its neurons to organize themselves in discrete assemblies, which through high‐frequency (>30 Hz) oscillations bind those distributed processes of the brain that are considered important, so that we are able to focus on what is needed from moment to moment and be aware of this fact. This ability is transiently lost in absence seizures, because large numbers of CT loops are recruited for seconds in much stronger, low‐frequency (∼3 Hz) oscillations of EPSP/IPSP sequences, which underlie electroencephalographic (EEG) spike‐and‐wave discharges (SWDs). These oscillations probably result from a transformation of the normal EEG rhythm of sleep spindles on an abnormal increase of cortical excitability that results in strong activation of inhibitory neurons in the cortex and in nucleus reticularis thalami. The strong general enhancement of CT feedback during SWDs may disallow the discrete feedback, which normally selects specific TC circuits for conscious perception and/or motor reaction. Such a mechanism of SWD generation allows variability in the extent to which different TC sectors are engaged in the SWD activity and thus explains the variable ability of some patients to respond during an absence, depending on the sensory modality examined.
Interactions Between Hormones and Epilepsy in Female Patients
Authors: Bauer Jürgen
Published: March 2003

Summary: Epilepsy and epileptic seizures may influence the release of hormones from the hypothalamus and the pituitary. After complex‐partial seizures or generalized tonic–clonic seizures, serum prolactin increases in about two thirds of cases. Apart from this transient effect, interictal epileptic discharges from the temporal lobe may exert a prolonged influence on hormone release. Changes in luteinizing hormone (LH) pulse frequency and increased prolactin levels have been reported. As a consequence, menstrual cycles may be disturbed. The cyclic change of sex serum hormones during the ovulatory menstrual cycle may have an impact on seizure occurrence during the days of ovulation and/or menstruation (e.g., catamenial seizures). By a supplementation of progesterone during the second half of anovulatory cycles, a decrease of seizure frequency can be achieved.
Long‐Term Safety of Tiagabine
Authors: Kälviäinen Reetta
Published: March 2003

Summary: Tiagabine (TGB) is now registered in >20 countries, and the total number of treated patients approaches 90,000. Short‐term safety data were derived mainly from five placebo‐controlled, add‐on studies in adults with therapy‐resistant partial epilepsy, and two conversion to TGB monotherapy studies. Central nervous system (CNS)‐related adverse effects, most frequently dizziness, were common with TGB treatment during the titration period; the risk became similar to placebo rates during fixed‐dose periods. Other adverse events that were more frequent in TGB‐ than in placebo‐treated patients were asthenia, nervousness, tremor, concentration difficulties, depressive mood, and language problems. TGB doses should be titrated slowly and taken with food to avoid rapid increases in plasma concentrations, thus minimizing the risks of adverse events. Overall, >2,500 patients have been exposed to TGB during clinical trials, with 1,274 patients treated >12 months, the majority of whom received TGB 24–60 mg/day. No idiosyncratic reactions have been linked to the use of TGB, and no abnormalities in hematology or common chemistry values were reported. In all the epilepsy studies combined, 21% of patients discontinued treatment because of adverse events, usually during the first 6 months of treatment. No adverse effects on cognitive abilities were detected when the neuropsychological effects of TGB add‐on therapy and monotherapy were evaluated. TGB does not appear to cause an excess risk of psychosis or increase the incidence of status epilepticus or spike/wave discharges. No evidence of a relationship between visual field constriction and TGB treatment was found in a study of 15 patients converted to TGB monotherapy (mean dose, 22 mg/day; mean duration, 2.5 years) who had a full ophthalmologic evaluation. In conclusion, the characteristics of TGB in the management of partial epilepsy are enhanced by its favorable side‐effect profile in the cognitive area.
Enhanced Anticonvulsant Activity of Neuroactive Steroids in a Rat Model of Catamenial Epilepsy
Authors: Reddy Doodipala S. , Rogawski Michael A.
Published: March 2003

Summary:  Purpose: Perimenstrual catamenial epilepsy may in part be due to withdrawal of the endogenous progesterone‐derived neurosteroid allopregnanolone that potentiates γ‐aminobutyric acidA (GABAA) receptor–mediated inhibition. Here we sought to determine whether the anticonvulsant potencies of neuroactive steroids, benzodiazepines, phenobarbital (PB), and valproate (VPA) are altered during the heightened seizure susceptibility accompanying neurosteroid withdrawal in a rat model of perimenstrual catamenial epilepsy.

Methods: Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5α‐reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50 values for protection against PTZ‐induced clonic seizures in naive young adult female rats.

Results: The anticonvulsant activity of allopregnanolone (5 mg/kg, s.c.), pregnanolone (5 mg/kg, s.c.), allotetrahydrodeoxycorticosterone (15 mg/kg, s.c.), and tetrahydrodeoxycorticosterone (10 mg/kg, s.c.) were enhanced by 34–127% after neurosteroid withdrawal. The anticonvulsant activity of PB (65 mg/kg, i.p.) was also enhanced by 24% in neurosteroid‐withdrawn animals. In contrast, the anticonvulsant activity of diazepam (4 mg/kg, i.p.), bretazenil (0.106 mg/kg, i.p.), and VPA (560 mg/kg, i.p.) were reduced or unchanged in neurosteroid‐withdrawn animals.

Conclusions: The anticonvulsant activity of neuroactive steroids is potentiated after neurosteroid withdrawal, supporting the use of such agents in the treatment of perimenstrual catamenial epilepsy.
Progression of Postictal to Interictal Psychosis
Authors: Tarulli Andrew , Devinsky Orrin , Alper Kenneth
Published: March 2003

Summary:  Purpose: To describe a case series of patients with both postictal psychosis (PIP) and chronic interictal psychosis (IIP).

Methods: We retrospectively reviewed the records of 43 patients with PIP from a comprehensive epilepsy center to find evidence of both PIP and IIP in the same patient.

Results: Six (13.9%) of the 43 patients met all the criteria for both PIP and IIP. Five of our six patients had multiple documented PIPs before they became chronically psychotic. The range of length of time between PIP and IIP was 7 to 96 months. Postictal and interictal psychotic behavior was similar or identical in five of six cases.

Conclusions: The results of this study suggest a progression from PIP to IIP: there is a similarity between the symptoms of the two psychoses, a history of multiple PIPs before the first IIP, and a period of months to years between PIP and IIP onset.
Peripheral WBC Count and Serum Prolactin Level in Various Seizure Types and Nonepileptic Events
Authors: Shah A. K. , Shein N. , Fuerst D. , Yangala R. , Shah J. , Watson C.
Published: March 2003

Summary:  Purpose: To analyze effects of different types of seizures and nonepileptic events as well as effects of seizure duration and lapse between the time of seizure and blood collection on serum prolactin level and peripheral white blood cell (WBC) count.

Methods: We prospectively collected blood samples from all patients admitted to our Epilepsy Monitoring Unit at baseline and after an event. Blood samples were analyzed, and serum prolactin level and WBC count were determined. Statistical analyses were performed to evaluate the relation of each type of seizure, its duration, and time lapse between a seizure and collection of blood sample to the serum prolactin level and peripheral WBC count.

Results: Serum prolactin level increases above twice the level at baseline after a complex partial seizure or a generalized seizure. Peripheral WBC count is elevated above the upper limit of normal in about one third of cases after a generalized seizure. In generalized seizures, the length of a seizure is positively associated, whereas the lapse time between the seizure onset and blood draw is negatively correlated with the increase in WBC count. Thus the longer the seizure and quicker the blood draw, the higher the WBC count.

Conclusions: We conclude that complex partial or generalized seizures are associated with an increase in serum prolactin level. Peripheral WBC count increases significantly after a generalized seizure and is probably transient in nature.
Adult‐Onset Idiopathic Generalized Epilepsy: Clinical and Behavioral Features
Authors: Cutting Shawna , Lauchheimer Aaron , Barr William , Devinsky Orrin
Published: March 2003

Summary:  Purpose: To identify and define clinical and behavioral features of patients with adult‐onset idiopathic generalized epilepsy (IGE).

Methods: We reviewed the charts of 313 IGE patients at the NYU Comprehensive Epilepsy Center over the past 5 years to identify patients with adult onset (18 years old or older). We excluded patients with childhood or adolescent symptoms that suggested absence, myoclonic, or tonic–clonic seizures, as well as those with a history of significant head injury or other known causes of localization‐related epilepsy.

Results: Forty‐two (13.4%) patients had a clear onset of IGE in adulthood; average age of onset was early 20s (mean, 23.8 years; range, 18–55 years). Twenty‐one patients had adult myoclonic epilepsy (AME, 50%), and three had generalized tonic–clonic seizures on awakening (GTCS‐A, 7%). More than two thirds (n = 30) are well controlled with current antiepileptic drugs (AEDs), and almost 90% are currently employed (n = 37). One third were diagnosed and treated for mental disorders, including depression (n = 12), anxiety (n = 7), obsessive–compulsive personality disorder (n = 2), and postictal psychosis (n = 1).

Conclusions: Adult‐onset IGE is associated with a good prognosis. An association may exist between psychological disorders, psychotropic medication, and level of seizure control in adults with IGE.
Seizure Semiology and Neuroimaging Findings in Patients with Midline Spikes
Authors: Kutluay Ekrem , Passaro Erasmo A. , Gomez‐Hassan Diana , Beydoun Ahmad
Published: March 2003

Summary:  Purpose: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes.

Methods: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification.

Results: Twenty‐nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases.

Conclusions: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.
Significance of Epileptiform Discharges in Patients without Epilepsy in the Community
Authors: Sam Maria C. , So Elson L.
Published: March 2003

Summary:  Purpose: To determine the frequency of recording epileptiform discharges (EDs) in patients without epilepsy in the community and to assess their risk of seizure disorders subsequently developing.

Methods: We identified all outpatient and inpatient EEGs that were recorded in persons residing in Rochester, Minnesota, from 1979 to 1988. Patients with a history of unprovoked seizure disorders before the index EEG were excluded. Periodic lateralized EDs (PLEDs) were not evaluated, because of their well‐established association with seizure disorders.

Results: Five hundred twenty‐one patients in the community had no history of unprovoked seizure disorders before their EEG. Sixty‐four (12.3%) patients had EDs; neither isolated unprovoked seizure nor epilepsy developed during 230.8 person‐years of follow‐up. Forty‐seven (73.4%) of the 64 patients had acute or progressive cerebral disorders when EEG detected EDs. Seizures that were acutely provoked by the underlying disorder (enlarging brain tumor, cerebral infarct, or bilateral subdural hematoma, in one patient each) subsequently developed in three (6.3%) of the 64 patients. Seizures of any type did not develop in the 17 patients without acute or progressive cerebral disorders.

Conclusions: In a community setting, EDs are sometimes observed in patients without epilepsy. However, nearly three fourths have underlying acute or progressive cerebral disorders. Acutely provoked seizures may develop in a small proportion of patients. Although none of our patients developed isolated unprovoked seizures or epilepsy, a longer period of follow‐up is needed to determine their risks relative to the general population.
Modification of Slow Cortical Potentials in Patients with Refractory Epilepsy: A Controlled Outcome Study
Authors: Kotchoubey B. , Strehl U. , Uhlmann C. , Holzapfel S. , König M. , Fröscher W. , Blankenhorn V. , Birbaumer N.
Published: March 2003

Summary:  Purpose: To compare self‐regulation of low‐frequency EEG components (slow cortical potentials, SCPs) with other methods of seizure control for patients with drug‐refractory partial epilepsy and to separate the real anticonvulsive effect from placebo effects.

Methods: Results of a treatment program of SCP self‐regulation (experimental group) are compared with two groups of patients, one of which learned self‐control of respiratory parameters (end‐tidal CO2 and respiration rate: RES group); the other received medication with new anticonvulsive drugs (AEDs) in combination with psychosocial counseling (MED group). Clinical, cognitive, behavioral, and personality measures were assessed before and after treatment. In addition, to control for placebo responses, patients repeatedly estimated their beliefs in the efficiency of the respective treatment, their satisfaction and expectations, and the quality of the relationship with their therapists.

Results: SCP and MED groups showed a significant decrease of seizure frequency, but the RES group did not. Clear positive changes in the sociopsychological adjustment were obtained in all three groups, with the maximal improvement being attained in the RES group.

Conclusions: All kinds of therapy result in considerable improvement of patients' emotional state, which may in part be due to potential placebo effects; however, this improvement is not related to the quality of the therapeutic effect proper (i.e., seizure reduction). Traditional double‐blind control group designs are inappropriate for behavioral interventions or treatments with psychoactive pharmacologic drugs. Rather, specific tests can be developed to control the placebo effect and to separate it from the genuine therapeutic effects.
Frontal Lobe Seizure Propagation: Scalp and Subdural EEG Studies
Authors: Blume Warren T. , Ociepa Dorota , Kander Veena
Published: March 2003

Summary:  Purpose: To study propagation properties of focally originating frontal lobe seizures: principally direction and promptness of ictal spread.

Method: Forty‐eight scalp EEG–recorded and 17 subdurally recorded seizures in two separate groups of patients were visually scrutinized.

Results: Initial propagation was directed more commonly to contiguous frontal cortex than to the opposite hemisphere in both studies: 58% and 86% for scalp and subdural recordings, respectively. Eighteen (38%) of scalp EEG seizures propagated within 5–10 s of apparent onset, whereas 16 (33%) did so after 11–20 s; no evidence of propagation could be discerned in the remaining 14 (29%). Of subdurally recorded attacks, only four (24%) propagated in the first 4 s; six (35%) did so after a delay of 5–10 s; six (35%) either failed to propagate or did so after ≥20‐s latency. Latency to initial propagation was between 5 and 20 s in 41 (63%) of the 65 seizures in both studies. Ictal activity remained within the frontal lobe of origin for ≥10 s in 39 (81%) of scalp‐recorded seizures and 11 (65%) of subdural seizures. It remained so confined for ≥15 s in 26 (54%) and nine (53%), respectively. Twenty‐four (50%) of scalp‐recorded seizures displayed evidence of opposite hemisphere (bisynchronous or other contralateral) involvement, occurring 5–10 s after onset in eight (17%) seizures and 10–20 s after onset in 16 (33%). Similarly, the subdural study documented spread to the opposite hemisphere in 11 (65%) of seizures with a latency ranging from 1 to 45 s.

Conclusions: Frontal lobe seizures in this study propagated less promptly than reputed, and initial spread occurred more commonly to the frontal lobe of origin than to the opposite hemisphere. Such properties underlie the good lateralizing value of clinical semiology of frontal lobe seizures.
Dipole Localization for Identification of Neuronal Generators in Independent Neighboring Interictal EEG Spike Foci
Authors: Ochi Ayako , Otsubo Hiroshi , Chitoku Shiro , Hunjan Amrita , Sharma Rohit , Rutka James T. , Chuang Sylvester H. , Kamijo Ken‐ichi , Yamazaki Toshimasa , Snead O. Carter
Published: March 2003

Summary:  Purpose: We evaluated dipole localizations of independent neighboring interictal spike foci using scalp electroencephalogram (EEG) to identify neuronal generators of epileptic discharges.

Methods: Three pediatric patients with extratemporal lobe epilepsy who had two independent neighboring interictal spike foci on scalp EEG were studied. Prolonged video EEG was digitally recorded from 19 scalp electrodes, whose positions were registered using a three‐dimensional digitizer. Interictal spikes were visually selected based on negative phase reversals on bipolar montages. We analyzed the dipole position and moment of each spike using a single moving dipole and three‐shell spherical head model. The dipoles were overlaid onto magnetic resonance (MR) images and divided into two groups based on two spike foci.

Results: The dipoles of the two groups were oriented either tangentially or radially to the scalp in close proximity to each other. The dipoles oriented radially were located underneath the electrode with a negative peak; those oriented tangentially were between electrodes with a negative and positive peak. The positions of tangential dipoles were more concentrated than those of radial dipoles. The epileptogenic regions corresponded to the dipole localizations. Surgical excisions were performed based on the results of electrocorticography. After surgery, two patients were seizure free, and one had rare seizures (follow‐up period, 13–31 months).

Conclusions: We showed that dipoles in close proximity but with different orientations projected two negative maxima on scalp EEG in three patients with extratemporal localization‐related epilepsy. Equivalent current dipole analysis of individual interictal spikes can provide useful information about the epileptogenic zone in these patients.
Ring 20 Chromosome Syndrome with Epilepsy and Dysmorphic Features: A Case Report
Authors: García Dolores María , Ortiz Rosario , Gómez Alicia , Barriuso Enrique
Published: March 2003

Summary: Relatively few cases of the 20 ring chromosome [r(20)] syndrome have been reported. Epileptic seizures, behavioral problems, mental retardation, and absence of definite dysmorphic features characterize this syndrome. We present a patient with the classic genetic and phenotypic findings. A 42‐month‐old boy with mild dysmorphic features and psychomotor retardation has had generalized tonic–clonic seizures, resistant to antiepileptic drug therapy since he was 26 months old. Electroencephalography (EEG) was performed on several occasions, as were brainstem auditory evoked potentials (BAEPs), magnetic resonance imaging (MRI), and cytogenetic studies. The EEG showed slow waves in anterior regions intermingled with spikes in temporal areas. The BAEPs were abnormal, and neuroimaging studies were normal. The chromosome r(20) appeared in 100 metaphases studied. Parental chromosomes were of normal karyotype. The genetic and EEG finding from this patient strongly suggest that epilepsy associated with 20 ring chromosome syndrome is a distinct new entity, although the clinical manifestations may be broader than previously recognized.
Altered Activities of Rat Brain Metabolic Enzymes in Electroconvulsive Shock—Induced Seizures
Authors: Eraković V. , Župan G. , Varljen J. , Laginja J. , Simonić A.
Published: March 2003

Summary:  Purpose: Electroconvulsive shock (ECS) induces generalized seizure activity and provides an excellent experimental model for studying the effects of global electrical stimulation on various biochemical parameters. The aim of this work was to investigate the influence of a single or repeated ECS‐induced seizures on rat brain metabolism.

Methods: Experiments were carried out on female Hannover—Wistar rats divided into four groups: (a) the control group, which was intact; (b) the 1ECS group, which was killed 2 h after single ECS; (c) the 5ECS group with 24 h rest, which was killed 24 h after the fifth daily ECS; and (d) the 10ECS group with 48 h rest, which was given ECS every 48 h and killed 24 h after the tenth ECS. Activities of glutamate dehydrogenase (GLDH), aspartate‐aminotransferase (AST), alanine‐aminotransferase (ALT), γ‐glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK) in the frontal cortex, cerebellum, hippocampus, and pons/medulla regions were determined.

Results: Increased AST, ALP, LDH, and CK activities were detected in all examined regions of the 1ECS and 5ECS groups. ALT activity was increased in both these groups, except in the hippocampus of the 5ECS group, where increased GGT activity was detected. In the hippocampus of 1ECS group, GLDH activity was decreased. Increased hippocampal AST and cortical CK activities, together with increased LDH activities in the cortex, cerebellum, and pons/medulla, were found.

Conclusions: ECS treatment induces region‐specific changes in metabolic activity. Neither a 24‐h nor a 48‐h rest period between two ECSs was sufficient for complete brain recovery, although most of the observed increased enzyme activities present in 1ECS and 5ECS were not present in 10ECS.
Efficacy of Clobazam as Add‐On Therapy in Patients with Refractory Partial Epilepsy
Authors: Montenegro M. A. , Cendes F. , Noronha A. L. A. , Mory S. B. , Carvalho M. I. , Marques L. H. N. , Guerreiro C. A. M.
Published: March 2003

Summary:  Purpose: Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first‐line drug in the treatment of epilepsy. We evaluated the efficacy of CLB as add‐on therapy in patients with refractory partial epilepsy.

Methods: This was an open, retrospective study, conducted at the epilepsy clinic of our university hospital. All patients had chronic epilepsy and were being evaluated for epilepsy surgery. CLB was introduced as add‐on therapy (starting with 10 mg/day) in patients with previous failure of at least two AEDs. Information was obtained from clinical notes and follow‐up visits.

Results: We evaluated 97 patients, 37 men and 60 women. Ages ranged from 15 to 70 years (mean, 35.8 years). Etiology of epilepsy was hippocampal atrophy in 67 (69%), cortical dysgenesis in nine (9.3%), and other etiologies in nine (9.3%). In 12 (12.3%) patients, the etiology of epilepsy was not identified despite clinical and neurologic investigation. Patients used CLB for a period ranging from 1 month to 7 years and 9 months (mean, 16.7 months) with doses ranging from 10 to 60 mg/day (mean, 29.7 mg/day). Seven (7.2%) patients were seizure free, 48 (49.4%) had ≥50% of improvement in seizure control, 39 (40.2%) had <50% of improvement in seizure control, and in three (3.1%), no data were available.

Conclusions: We conclude that CLB may have efficacy equivalent to that of the new AEDs when used as add‐on therapy in patients with refractory epilepsy. CLB should be considered an economic alternative in the treatment of patients with refractory epilepsy.
Tiagabine: Efficacy and Safety in Adjunctive Treatment of Partial Seizures
Authors: Crawford P. , Meinardi H. , Brown S. , Rentmeester TH. W. , Pedersen B. , Pedersen P. C. , Lassen L. C.
Published: March 2003

Summary:  Purpose: To assess the efficacy and safety of tiagabine (TGB), a new antiepileptic drug (AED), as add‐on therapy in patients with refractory partial seizures.

Methods: This response‐dependent study used an open‐label screening phase (in which patients were titrated to their optimal TGB dose, ≤64 mg/day) followed by a double‐blind, placebo‐controlled, crossover phase. Initial eligibility criteria included (a) seizures inadequately controlled by existing AEDs, and (b) six or more partial seizures during an 8‐week baseline period. Patients showing benefit from TGB (≥25% reduction in total seizure rate relative to baseline) were eligible for randomization into the double‐blind phase, which comprised two 7‐week assessment periods separated by a 3‐week crossover period.

Results: Forty‐four (50%) of the 88 enrolled patients entered the double‐blind phase of the study during which there were significant reductions compared with placebo in all partial (p < 0.01), complex partial (p < 0.001), and secondarily generalized tonic–clonic seizure rates (p < 0.05). Thirty‐three percent of patients experienced a reduction of ≥50% in the all partial seizure rate. Eight (22%) patients receiving TGB during the double‐blind phase reported adverse events, of which dizziness and incoordination were the most frequent. Three patients withdrew from treatment during the double‐blind phase because of adverse events; two during treatment with TGB and one during treatment with placebo. TGB did not affect plasma concentrations of other coadministered AEDs.

Conclusions: TGB was significantly better than placebo in terms of seizure rate reduction and was generally well‐tolerated in patients with difficult to control seizures.
Social Functioning, Psychological Functioning, and Quality of Life in Epilepsy
Authors: Suurmeijer Theo P. B. M. , Reuvekamp Marieke F. , Aldenkamp Bert P.
Published: March 2003

Summary:  Purpose: Part of our research intended to explain “Quality of Life” (QoL) differences between people with epilepsy. To this end, a series of already existing generic and disease‐specific health status measures were used. In this study, they were considered as determinants of people's QoL, whereas QoL itself was conceived as a general “value judgment” about one's life.

Methods: From the records of four outpatient clinics, 210 persons with epilepsy were randomly selected. During their visit to the outpatient clinic, they completed a questionnaire assessing, among other things, health perceptions and social and psychological functioning. Additional information about their medical and psychosocial status was gathered from the patient files. Data were analysed by using a hierarchical regression analysis.

Results: In decreasing order of importance, “psychological distress,”“loneliness,”“adjustment and coping,” and “stigma perception” appeared to contribute most significantly to the outcome QoL as judged by the patients themselves, regardless of their physical status. In the final model, none of the clinical variables (onset, seizure frequency, side effects of antiepileptic drugs) contributed significantly anymore to the patients' “quality‐of‐life judgement.” Apparently the effect of other variables such as seizure frequency and health perceptions, medication and side effects, life fulfilment, self‐esteem, and mastery is mediated by these variables.

Conclusions: Because all of the variance in QoL of the patients was explained by the psychosocial variables included in this study, health professionals should be aware of the significance of the psychosocial functioning of the patients and the role it plays in the achievement of a good QoL. Both informal and professional support may be an adjunct to conventional treatment. In future research, this issue should be given high priority.
Long‐Term Valproate and Lamotrigine Treatment May Be a Marker for Reduced Growth and Bone Mass in Children with Epilepsy
Authors: Guo Chun‐Yuan , Ronen Gabriel M. , Atkinson Stephanie A.
Published: March 2003

Summary:  Purpose: To determine whether long‐term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism.

Methods: Twenty‐seven boys and 26 girls, aged 3 to 17 years (9.2 ± 3.9, mean ± SD), with epilepsy treated with VPA and/or LTG for ≥2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism.

Results: Twenty‐three (43.4%) of the children had a body height below the 10th percentile. Z‐scores for BMD below –1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z‐score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25‐hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z‐score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25‐dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG‐alone, VPA‐alone, and LTG‐plus‐VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA‐plus‐LTG treatment group.

Conclusions: Long‐term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.
Lack of Association Between an Interleukin 1 Beta (IL‐1β) Gene Variation and Refractory Temporal Lobe Epilepsy
Authors: Buono Russell J. , Ferraro Thomas N. , O'Connor Michael J. , Sperling Michael R. , Ryan Stephen G. , Scattergood Theresa , Mulholland Nicole , Gilmore Joan , Lohoff Falk W. , Berrettini Wade H.
Published: March 2003

Summary:  Purpose: We attempted to confirm recent findings of Kanemoto et al. that demonstrated a positive association (p < 0.017) between a polymorphism in the promoter region of the interleukin 1‐β (IL‐1β) gene and the clinical phenotype of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS).

Methods: We determined the frequency of this polymorphism in a group of 61 TLE+HS patients of European ancestry and compared it with that found in 119 ethnically matched control subjects.

Results: Analysis of genotype and allele frequencies showed no statistically significant difference in the distribution of the polymorphism between the two groups (p = 0.10).

Conclusions: These data suggest that this IL‐1β promoter polymorphism does not act as a strong susceptibility factor for TLE+HS in a population of individuals of European ancestry.
Long‐Term Seizure Outcome and Antiepileptic Drug Treatment in Surgically Treated Temporal Lobe Epilepsy Patients: A Controlled Study
Authors: Bien Christian G. , Kurthen Martin , Baron Karin , Lux Silke , Helmstaedter Christoph , Schramm Johannes , Elger Christian E.
Published: March 2003

Summary:  Purpose: To evaluate the long‐term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE).

Methods: Comparison of seizure outcome and AED us in operated‐on TLE patients (n = 148) and nonsurgically treated TLE patients (n = 94) at a baseline visit and a follow‐up visit after a mean period of 4.8 years.

Results: At follow‐up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure‐ free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated‐on and 3.2% of the not operated‐on patients had been seizure‐free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow‐up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated‐on than in non–operated‐on patients. Further subgroup analysis revealed that not only the continuously seizure‐free surgical patients, but also the operated‐on patients with ongoing seizures took fewer AEDs than their respective non–operated‐on counterparts.

Conclusions: This controlled study for the first time provides comprehensive information on long‐term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure‐free patient subgroup.
Low Serum Biotinidase Activity in Children with Valproic Acid Monotherapy
Authors: Schulpis K. H. , Karikas G. A. , Tjamouranis J. , Regoutas S. , Tsakiris S.
Published: March 2003

Summary:  Purpose: Valproic acid (VPA) is an effective antiepileptic drug (AED), which is associated with dose‐related adverse reactions such as skin rash, hair loss (alopecia), etc. Profound as well as partial biotinidase deficiency causes dermatologic manifestations similar these. Therefore, it was of interest to evaluate serum biotinidase activity in patients receiving VPA monotherapy.

Methods: Seventy‐five patients with seizures, mean age, 8.6 years (±1.9 years) were divided into three groups. Group A (n = 25) was treated with VPA 28.7 ± 8.5 mg/kg/24 h, group B (n = 25) with 41.6 ± 4.9 mg/kg/24 h, and group C with 54.5 ± 5.8 mg/kg/24 h. Their “trough” VPA serum levels were 40.9 ± 13.2, 86.25 ± 11.5, and 137 ± 14.5 μg/ml, respectively. Fifty healthy children were the controls. Patients and controls underwent clinical and laboratory evaluations including liver function data, complete blood counts, NH3, and so on, after 45 days of VPA treatment. Biotinidase serum levels were evaluated fluorometrically.

Results: Liver function data were found elevated in the groups B and C. On the contrary, biotinidase activity was significantly statistically lowered (p < 0.001) in groups B and C (1.22 ± 1.11, 0.97 ± 0.07 mmol/min/L respectively), as compared with controls (5.20 ± 0.90 mmol/min/L). Strong inverse correlations were observed between liver enzymes and VPA blood levels with the activity of the enzyme. Additionally, no inhibitory effect on biotinidase activity was found, when the enzyme was incubated in vitro with high (1.2 mM) concentrations of the drug. Skin lesions (seborrheic rash, alopecia) were improved in our patients after biotin (10 mg/day) supplementation.

Conclusions: It is suggested that VPA impairs the liver mitochondrial function, resulting in a low biotinidase activity and or biotin deficiency. Biotin supplementation could restore some of the side effects of the drug.
Seizures after Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Passero Stefano , Rocchi Raffaele , Rossi Símone , Ulivelli Monica , Vatti Giampaolo
Published: March 2003

Summary:  Purpose: To characterize seizures after intracerebral hemorrhage (ICH), evaluating the risk of occurrence and relapse, predisposing factors, and prognostic significance, and to assess the utility of antiepileptic drug (AED) therapy as used in clinical practice.

Methods: The study sample consisted of 761 patients with spontaneous, nonaneurysmal, supratentorial ICH. Seizures were classified as immediate (within 24 h of ICH) and early (within 30 days of ICH). Baseline variables and clinical events were compared in the seizure and nonseizure group by using a multivariate regression model of failure time data.

Results: Fifty‐seven patients had one or more seizures. The 30‐day actuarial risk of a post‐ICH seizure was 8.1%. Lobar location and small volume of ICH were independent predictors of immediate seizures. Early seizures were associated with lobar location and neurologic complications, mainly rebleeding. In patients with lobar ICH, the risk of early seizures was reduced by prophylactic AED therapy. Among seizure patients, history of alcohol abuse increased the risk of status epilepticus. Immediate and early seizures were not independent predictors of in‐hospital mortality.

Conclusions: Patients with ICH are exposed to a substantial risk of seizures; however, short‐term mortality was not affected, and the risk of epilepsy was lower than previously thought. The likelihood of immediate seizures is influenced by factors that are inherent characteristics of ICH, whereas the chance of developing early seizures is influenced not only by certain characteristics of ICH, but also by unpredictable events. A brief period of therapy soon after ICH onset may reduce the risk of early seizures in patients with lobar hemorrhage.
Epileptic Spikes: Magnetoencephalography versus Simultaneous Electrocorticography
Authors: Oishi Makoto , Otsubo Hiroshi , Kameyama Shigeki , Morota Nobuhito , Masuda Hiroshi , Kitayama Masaomi , Tanaka Ryuichi
Published: March 2003

Summary:  Purpose: To test the sensitivity of extracranial magnetoencephalography (MEG) for epileptic spikes in different cerebral sites.

Methods: We simultaneously recorded MEG and electrocorticography (ECoG) by using subdural electrodes with 1‐cm interelectrode distances for one patient with lateral frontal epilepsy and one patient with basal temporal epilepsy. We analyzed MEG spikes associated with ECoG spikes and compared the maximal amplitude and number of electrodes involved. We estimated and evaluated the locations and moments of the equivalent current dipoles (ECDs) of MEG spikes.

Results: In patient 1, MEG detected 100 (53%) of 188 ECoG lateral frontal spikes, including 31 (46%) of 67 spikes that activated three subdural electrodes. MEG spike amplitudes correlated with ECoG spike amplitudes and the number of electrodes activated (p < 0.01). ECDs were perpendicular to the superior frontal sulcus. In patient 2, MEG detected 31 (26%) of 121 ECoG basal temporal spikes, but none that activated only three subdural electrodes. ECDs were localized in the entorhinal and parahippocampal gyri, oriented perpendicular to those basal temporal cortical surfaces. The ECD strength was 136.6 ± 71.5 nAm in the frontal region, but 274.5 ± 150.6 nAm in the temporal region (p < 0.01).

Conclusions: When lateral frontal ECoG spikes extend >3 cm2 across the fissure, MEG can detect >50%, correlating with spatial activation and voltage. In the basal temporal region, MEG requires higher‐amplitude discharges over a more extensive area. MEG shows a significantly higher sensitivity to lateral convexity epileptic discharges than to discharges in isolated deep basal temporal regions.
Gabapentin Increases Slow‐wave Sleep in Normal Adults
Authors: Foldvary‐Schaefer Nancy , De Leon Sanchez Isabel , Karafa Matthew , Mascha Ed , Dinner Dudley , Morris Harold H.
Published: March 2003

Summary:  Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid‐eye‐movement (REM) sleep, slow‐wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep.

Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow‐up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test.

Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP‐treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects.

Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption.