bluuebunny/crossref_metadata_2025 huggingface dataset:
Benign Partial Seizures of Adolescence
Authors: King Mark A. , Newton Mark R. , Berkovic Samuel F.
Published: August 2005

Summary: Purpose: A benign syndrome of partial seizures in adolescents (BPSA) was described by Loiseau et al. in 1978, but confirmation of this syndrome has been lacking. We sought to identify BPSA among teenagers with new‐onset focal seizures enrolled in our prospective first‐seizure study and to assess the EEG and magnetic resonance imaging (MRI) findings.

Methods: We searched the study database for patients aged between 10 and 20 years with focal seizures who did not have idiopathic partial epilepsies, epileptogenic lesions on MRI, or recurrent tonic‐clonic seizures during 2 years of follow‐up.

Results: The database contained 92 adolescents, including 37 with partial epilepsy, of whom eight (22%) patients matched the description of BPSA. All eight patients had seizures with a sensory/motor “march.” Six had a secondarily generalized seizure and two had simple partial seizures alone. Epileptiform abnormalities were documented in five cases but lacked a distinctive morphology or distribution. No lesions were seen on MRI.

Conclusions: BPSA can be provisionally diagnosed in teenagers with unprovoked focal seizures characterized by a march of sensory/motor symptoms, whose MRI is normal. The psychosocial consequences of chronic epilepsy in adolescence are considerable, so early recognition of this benign syndrome is important.
Functional Magnetic Resonance Imaging Identifies Abnormal Visual Cortical Function in Patients with Occipital Lobe Epilepsy
Authors: Masuoka Lorianne K. , Anderson Adam W. , Gore John C. , McCarthy Gregory , Spencer Dennis D. , Novotny Edward J.
Published: August 2005

Summary: Purpose: To determine whether functional magnetic resonance imaging (fMRI) can reliably identify lateralized cortical dysfunction in patients with suspected occipital lobe epilepsy.

Methods: We compared visual cortical function of 10 patients with intractable occipital lobe epilepsy with nine control subjects' fMRI. Visual stimulation by using an alternating checkerboard pattern results in transient increases in the intensity of the proton magnetic resonance signal of water in the occipital lobes during echo‐planar imaging. We used these stimulus‐dependent changes in signal intensity to construct functional activation maps, which we registered onto anatomic images.

Results: After full‐field stimulation, none of the patients with occipital lobe epilepsy had normal activation patterns, whereas eight of the nine control subjects had normal patterns (p = 0.001). Abnormalities consisted of either a markedly asymmetric activation pattern in six of 10 patients (p = 0.04), or a complete absence of activation in four of 10 patients (p = 0.05). The abnormal side of activation was concordant with the side of seizure onset in all six patients with asymmetric activation maps. Half‐field stimulation produced less reliable results. Although more patients had abnormal activation maps than did controls with half‐field stimulation (p = 0.04), the abnormal side was discordant with the side of seizure onset in three of the five patients who had markedly asymmetric activation patterns.

Conclusions: These results suggest that fMRI with full‐field stimulation is a reliable, noninvasive method for identifying areas of abnormal visual cortical function ipsilateral to the epileptogenic region in patients with occipital lobe epilepsy.
Status Epilepticus‐induced Neuronal Injury and Network Reorganization
Authors: Sloviter Robert S.
Published: August 2005

It is now evident that prolonged febrile seizures in childhood, or an episode of status epilepticus at any age, can produce the highly characteristic pattern of hippocampal cell loss and shrinkage that is seen later in life, when patients develop temporal lobe epilepsy. Seizure‐induced and presumably excitotoxic pathology includes neuronal loss, reactive gliosis, aberrant synaptic reorganization of surviving cells, and hippocampal tissue shrinkage that may alter extracellular space and affect ionic homeostasis. Whether any of these pathological effects of prolonged excitation play a causal role in the epileptogenic process that ultimately leads to spontaneous afebrile seizures remains a subject of intense interest. Two hypotheses have been suggested to explain how seizure‐induced neuronal loss might initiate the epileptogenic process. One hypothesis suggests that normal inhibition and excitability is maintained by vulnerable non‐principal cells, and that their loss deactivates inhibitory neurons, rendering principal cells disinhibited and hyperexcitable. The other hypothesis regards the initial loss as a stimulus for normally unconnected principal cells to form aberrant recurrent excitatory connections. Additional influences undoubtedly include a “kindling” process that gradually overcomes polysynaptic inhibition, and changes in extracellular space that may facilitate synaptic and ephaptic depolarization. Identification of the suspected substrates of epileptogenesis will serve as a stimulus for future progress and provide direction for new experimental designs.
Social Phobia: Issues in Assessment and Management
Authors: Connor Kathryn M. , Davidson Jonathan R. T. , Sutherland Suzanne , Weisler Richard
Published: August 2005

Social phobia was initially classified with phobic anxiety states and was believed to be quite rare, but it is now gaining due recognition as a widespread and often crippling disorder. The boundaries of social phobia merge into traits of shyness and universal performance anxiety, with symptoms commonly appearing in the teenage years. If left untreated, social phobia is a remarkably persistent condition, leading to potentially lifelong impairment in social development and occupational functioning. It may also give rise to other co‐morbid disorders, particularly dysthymia, depression, obsessive‐compulsive disorder, other phobic disorders, and substance abuse. Over the years, social phobia has been all too frequently viewed as a somewhat trivial, minor form of psychiatric illness and has received little clinical attention. This erroneous perception is now giving way under the mounting evidence in support of the extensive morbidity and disability associated with social phobia and the probable role of genetic and environmental influences. Furthermore, data from multiple controlled clinical trials reveal that this is a treatable condition, responding to both psychosocial and pharmacologic interventions. Here we examine issues to consider in the differential diagnosis of social phobia, review the goals of treatment, and summarize evidence in support of the effectiveness of individual pharmacologic treatments.
Efficacy of Five Days’ Barbiturate Anesthesia in the Treatment of Intractable Epilepsies in Children
Authors: Rantala Heikki , Saukkonen Anna‐Liisa , Remes Mikko , Uhari Matti
Published: August 2005

Summary: Purpose: To analyze the efficacy of barbiturate anesthesia in the treatment of intractable epilepsies in childhood.

Methods: Anesthesia for 4–5 days with thiopentone sodium was used to treat children with intractable epilepsy in the Department of Pediatrics, Oulu, Finland, from November 1980 through December 1995. The number of epileptic seizures, the number and dosage of antiepileptic drugs (AEDs), and psycho‐motor development before and after anesthesia were compared.

Results: Fifty‐four children with intractable epilepsy were treated with barbiturate anesthesia. Twenty‐four children had infantile spasms; 22, Lennox‐Gastaut syndrome; seven, complex partial epilepsy; and one, myoclonic epilepsy. Twentyfour (44.4%) children had complications during the anesthesia. The seizures recurred in 53 of the 54 patients in a median time of 12 days after the anesthesia. In 42 (78%) children, the seizure frequency returned to a level equal to or higher than that before the anesthesia in a median time of 211 days. The number of AEDs was significantly greater after than before the anesthesia (6.33 vs. 4.8; p < 0.001). Seventeen (32.5%) children were treated surgically after the anesthesia.

Conclusions: Although the seizures are eliminated or the seizure frequency decreases for a short period after the barbiturate anesthesia, the anesthesia does not change the long‐term outcome and is therefore inefficient in the treatment of childhood intractable epilepsies.
The Association Between Seizure Clustering and Convulsive Status Epilepticus in Patients with Intractable Complex Partial Seizures
Authors: Haut Sheryl R. , Shinnar Shlomo , Moshé Solomon L. , O'Dell Christine , Legatt Alan D.
Published: August 2005

Summary: Purpose: We examined the association between seizure clustering and convulsive status epilepticus (SE) in patients with intractable complex partial seizures, to identify whether patients whose seizures typically cluster are at high risk for convulsive SE (CSE).

Methods: Seventy‐six patients with intractable complex partial epilepsy who underwent presurgical evaluation in the Montefiore Epilepsy Management Unit from 1993 to 1997 were contacted and interviewed about typical seizure frequency and distribution and history of CSE. Seizure clustering was defined as three or more complex partial seizures within a 24‐h period, with return to baseline between seizures.

Results: Of the 76 patients contacted, 21 (28%) had experienced at least one episode of CSE, and 36 (47%) typically experienced clustered seizures. SE occurred in 16 (44%) of 36 patients with clustered seizures, and in five (12.5%) of 40 patients with nonclustered seizures (p < 0.002). Of 53 patients with temporal lobe epilepsy, CSE occurred in 13 (50%) of 26 patients with clustered seizures, and four (14.8%) of 27 patients with nonclustered seizures (p < 0.006).

Conclusions: Patients with intractable complex partial or localization‐related epilepsy who typically experience seizure clustering are at a significantly higher risk for CSE than are patients with nonclustered seizures.
Correlation of Hippocampal Neuronal Density and FDG‐PET in Mesial Temporal Lobe Epilepsy
Authors: Foldvary N. , Lee N. , Hanson M. W. , Coleman R. E. , Hulette C. M. , Friedman A. H. , Bej M. D. , Radtke R. A.
Published: August 2005

Summary: Purpose: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60–80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE.

Methods: Forty‐three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG‐PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal‐Wallis one‐way analysis of variance (ANOVA).

Results: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG‐PET had higher neuronal density in CA2 and CA3 versus patients with normal studies.

Conclusions: This study supports a previous observation that degree of FDG‐PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.
The Pharmacologic Basis of Antiepileptic Drug Action
Authors: Rho Jong M. , Sankar Raman
Published: August 2005

Summary: The development of medications used in the treatment of epilepsy has accelerated over the past decade, and has benefited from a parallel growth in our knowledge of the basic mechanisms underlying neuronal excitability and synchronization. This understanding of the pharmacologic basis of antiepileptic drug (AED) action has, in large part, arisen from recent advances in cellular and molecular biology, coupled with avenues of drug discovery that have departed somewhat from the largely empiric approaches of the past. Physicians now have available to them an ever‐growing armentarium of AEDs, necessitating a firmer appreciation of their mechanisms of action if more rational approaches toward both clinical application and research are to be adopted. An important example in this regard is the concept of rational polypharmacy for patients with epilepsy who are refractory to monotherapy. This review summarizes our current understanding of the molecular targets of clinically significant AEDs, comparing and contrasting their differing mechanisms of action.
Noninvasive Continuous Monitoring of Cerebral Oxygenation Periictally Using Near‐Infrared Spectroscopy: A Preliminary Report
Authors: Adelson P. David , Nemoto Edwin , Scheuer Mark , Painter Michael , Morgan John , Yonas Howard
Published: August 2005

Summary: Purpose: To report on the use of near‐infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures.

Methods: Cerebral hemoglobin oxygen availability was monitored continuously and noninvasively with NIRS in three patients (one in the pediatric intensive care unit (ICU) and two in epilepsy‐monitoring units) in conjunction with continuous EEG monitoring. Ictal events were recorded and compared with the pre‐, intra‐, and postictal periods for cerebral oxygen availability, as defined by oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and the redox state of cytochrome oxidase (cytox).

Results: Several important preliminary observations were made by using this technology. First, a preictal increase in cerebral oxygenation began between 1 and 2 h and <10 h before the ictal event. Second, despite adequate perfusion, based on an observed increased HbO2, reduction in cytox indicates a perfusion‐metabolism mismatch during seizure activity. Third, continued seizure activity and even isolated ictal events were associated with decreased cerebral oxygen availability. Fourth, differences in cerebral oxygen availability were noted between different types of seizures (e.g., electrographic seizures were accompanied by rapid reductions in HbO2 and cerebral blood volume without reduction of cytox, whereas electroclinical seizures were characterized by marked increases in HbO2 with or without reduction of cytox).

Conclusions: In this preliminary report on the use of NIRS for patients with seizures, we believe that NIRS allows continuous and noninvasive monitoring of changes in cerebral oxygenation periictally, thereby permitting investigations into the pathophysiology of seizures and the exploration of the potential of cerebral oximetry as a tool for seizure localization.
Lateralizing Value of Interictal Spikes on Overnight Sleep‐EEG Studies in Temporal Lobe Epilepsy
Authors: Malow Beth A. , Selwa Linda M. , Ross Donald , Aldrich Michael S.
Published: August 2005

Summary: Purpose: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep‐EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non‐rapid eye movement (NREM) sleep than in wakefulness, overnight sleep‐EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs.

Methods: Twenty‐four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep‐EEG recordings. Subjects were seizure free ≤24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long‐term monitoring, brain magnetic resonance images (MRIs), and surgical outcome.

Results: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (<95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal‐onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal‐onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal‐onset regions had good to excellent surgical outcomes.

Conclusions: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.
An Open‐Label Study of Repeated Use of Diazepam Rectal Gel (Diastat) for Episodes of Acute Breakthrough Seizures and Clusters: Safety, Efficacy, and Tolerance
Authors: Mitchell Wendy G. , Conry J. A. , Crumrine P. K. , Kriel R. L. , Cereghino J. J. , Groves L. , Rosenfeld W. E. ,   North American Diastat Group
Published: August 2005

Summary: Purpose: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of ≤5 days.

Methods: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single‐use, prefilled syringe; dosage was determined by age and weight. Maximal use was ≤5‐day intervals, ≥5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly.

Results: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty‐five received two or more treatments (two to 78; median, 8), 0.03–4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months.

Conclusions: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication‐related AEs were seen with repeated DZPRG administration at intervals ≤5 days.
Stiripentol: Efficacy and Tolerability in Children with Epilepsy
Authors: Perez J. , Chiron C. , Musial C. , Rey E. , Blehaut H. , D'Athis P. , Vincent J. , Dulac O.
Published: August 2005

Summary: Purpose: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450′ resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add‐on therapy in children were assessed.

Methods: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single‐blind, placebo‐controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial).

Results: Among the 97 patients who could be analyzed for efficacy in the placebo‐controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p > 0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p > 0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30‐month follow‐up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication.

Conclusions: STP seems to be a promising add‐on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.
Two Different Anticonvulsant Actions of Tiagabine in Developing Rats
Authors: Haugvicová R. , Škutová M. , Kubová H. , Suchomelová L. , Mareš P.
Published: August 2005

Summary: Purpose: Our goal was to study the anticonvulsant action of tiagabine (TGB) at different levels of brain maturation in rats.

Methods: Wistar rats in five age groups (7, 12, 18, 25, and 90 days old) were injected intraperitoneally with TGB at doses of 0.5–32 mg/kg. Thirty minutes later, motor seizures were induced by the subcutaneous adminstration of pentylenetetrazol (PTZ) in a dose of 100 mg/kg for all of the groups except the 18‐day‐old rat pups, which received a 90‐mg/kg dose. The incidence and latency of two types of motor seizures, minimal clonic and generalized tonic‐clonic seizures (GTCSs), were evaluated, and the seizure severity was scored. The time profile of TGB action at the 8‐mg/kg dose was studied in the 12‐ and 25‐day‐old rats.

Results: Minimal clonic seizures were reliably induced in rats 18 days old or older, and the seizures were suppressed by TGB in all of these age groups. Although TGB was very effective against this type of seizure in the 18‐day‐old rats, the efficacy of the drug decreased with the age of the animal. GTCSs were suppressed by TGB in the adult and 25‐day‐old rats, and a U‐shaped dose‐response curve was outlined in these two groups. The 18‐ and 12‐day‐old rat pups exhibited a selective suppression of the tonic phase of GTCSs. A mixture of these two effects was observed in the youngest group. TGB demonstrated a markedly longer action in the 12‐day‐old rats than in the 25‐day‐old rats.

Conclusions: TGB exhibits anticonvulsant action against both minimal seizures and GTCSs. Ontogenetic development of these two actions is markedly different.
Subacute Electrical Stimulation of the Hippocampus Blocks Intractable Temporal Lobe Seizures and Paroxysmal EEG Activities
Authors: Velasco Marcos , Velasco Francisco , Velasco Ana Luisa , Boleaga Bernardo , Jimenez Fiacro , Brito Francisco , Marquez Irma
Published: August 2005

Summary: Purpose: To investigate the clinical, electroen‐cephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyms (SAHCS) on 10 patients with intractable temporal lobe seizures.

Methods: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, anti‐epileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2–3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 130/s in frequency, 450 μs in duration, and 200–400 μA in amplitude. The stimuli were delivered 23 of every 24 h for the 2–3–week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10–second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light‐microscopy studies.

Results: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation program, SAHCS abolished clinical seizures and significantly decreased the number of interictal EEG spikes at the focus after 5–6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow‐wave sleep in surface, depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was administered outside the hippocampus.

Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth‐electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue.

Conclusions: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.
Seizures Provoked by Blows to the Head
Authors: Clear Daniela , Chadwick David W.
Published: August 2005

Summary: The nonepileptic nature of convulsions occurring within seconds of head injury has been commented on. However, we have recently seen a patient in whom relatively trivial blows to the head did seem to give rise to epileptic seizures.
The Anticonvulsant SGB‐017 (ADCI) Blocks Voltage‐Gated Sodium Channels in Rat and Human Neurons: Comparison with Carbamazepine
Authors: Sun Lucy , Lin Stephen S.
Published: August 2005

Summary: Purpose: SGB‐017 (ADCI) is a novel anticonvul‐sant that blocks both voltage‐activated sodium channels and N‐methyl‐d‐aspartate (NMDA)‐receptor‐gated channels. Results by Rogawski et al. suggested that SGB‐017 produces its anticonvulsant action primarily by inhibition of NMDA‐receptor channels. However, SGB‐017 is effective in several animal models of epilepsy that are unresponsive to NMDA antagonists. These results indicate that block of NMDA‐receptor channels is not the only mechanism contributing to its anticonvulsant activity. Thus the effects of SGB‐017 on neu‐ronal sodium channels were investigated.

Methods: Whole cell voltage‐clamp techniques were used to record sodium currents in freshly dissociated rat superior cervical ganglion (SCG) and hippocampal neurons and cultured human NT2 neurons. The effects of SGB‐017 on the amplitude of sodium currents, elicited by a depolarizing pulse to 0 mV from different holding potentials, were measured and compared with those of carbamazepine (CBZ).

Results: SGB‐017 inhibited sodium currents in rat SCG and hippocampal neurons with a similar potency to CBZ. Like CBZ, the inhibition of sodium channels by SGB‐017 was voltage dependent. Its median inhibitory concentration (IC50) for inhibition of sodium channels at depolarized holding potentials is similar to that for its inhibition of NMDA receptor channels. In human hNT2 neurons, SGB‐017 was more potent than CBZ at inhibiting sodium currents.

Conclusions: SGB‐017 produces its anticonvulsant activity by blocking both sodium‐ and NMDA‐receptor channels in a voltage‐ and use‐dependent manner. The combination of these two mechanisms of action makes SGB‐017 an effective AED in several different animal models of epilepsy.
Cyclosporine Induces Epileptiform Activity in an In Vitro Seizure Model
Authors: Wong Michael , Yamada Kelvin A.
Published: August 2005

Summary: Purpose: Cyclosporine (CSA) toxicity represents a common cause of seizures in transplant patients, but the specific mechanisms by which CSA induces seizures are unknown. Although CSA may promote seizure activity by various metabolic, toxic, vascular, or structural mechanisms, CSA also has been hypothesized to modulate neuronal excitability directly. The objective of this study was to determine if CSA exerts direct epileptogenic actions on neurons in an in vitro seizure model.

Methods: Combined hippocampal‐entorhinal cortex slices from juvenile rats were exposed directly to artificial cerebro‐spinal fluid (ACSF) containing either (a) 1.0 mM magnesium sulfate (control), (b) 1.0 mM sodium sulfate (low‐magnesium), or (c) 1.0 mM magnesium sulfate + CSA (1,000–10,000 ng/ml). Spontaneous and evoked extracellular field potentials were recorded simultaneously from the dentate gyrus (DG) and CA3 hippocampal regions. Evoked synaptic responses were elicited by stimulation of the entorhinal cortex/perforant pathway.

Results: CSA elicited spontaneous or stimulation‐induced epileptiform activity in the DG or CA3 region of –40% of slices, consisting of brief repetitive “interictal” discharges or prolonged stereotypical “ictal” discharges. Mean latency to epileptiform activity was –100 min after onset of CSA application. The interictal discharges were inhibited by the non‐NMDA antagonist, NBQX. Similar epileptiform activity was observed in low‐magnesium ACSF without CSA. In control ACSF alone, epileptiform activity was not seen, except for rare spontaneous potentials in the DG.

Conclusions: Direct effects of CSA on neuronal excitability and synaptic transmission may contribute to seizures seen in clinical CSA neurotoxicity.
The Role of Intracranial Electrode Reevaluation in Epilepsy Patients After Failed Initial Invasive Monitoring
Authors: Siegel Adrian M. , Roberts David W. , Thadani Vijay M. , McInerney James , Jobst Barbara C. , Williamson Peter D.
Published: August 2005

Summary: Purpose: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery.

Methods: A series of 110 consecutive patients with partial epilepsy who had undergone intracranial electrode evaluation (by subdural strip, subdural grid, and/or depth electrodes) between February 1992 and October 1998 was retrospectively analyzed. Of these, failed localization of seizure origin was thought to be due to sampling error in 13 patients. Nine of these 13 patients underwent a second intracranial investigation.

Results: Reevaluation with intracranial electrodes resulted in satisfactory seizure‐onset localization in seven of nine patients, and these seven had epilepsy surgery. Three frontal, two temporal, and one occipital resection as well as one multiple subpial transection were performed. Six patients have become seizure free, and one was not significantly improved. The mean follow‐up is 2.8 years. There was no permanent morbidity.

Conclusions: In selected patients in whom invasive monitoring fails to identify the site of seizure origin, reinvestigation with intracranial electrodes can achieve localization of the region of seizure onset and allow successful surgical treatment.
Proton Magnetic Resonance Spectroscopic Imaging Studies in Patients with Newly Diagnosed Partial Epilepsy
Authors: Li Li Min , Dubeau François , Andermann Frederick , Arnold Douglas L.
Published: August 2005

Summary: Purpose: To assess whether the N‐acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr.

Patients and Methods: Proton magnetic resonance spectro‐scopic imaging (1H‐MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow‐up 1H‐MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging.

Results: Initial 1H‐MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow‐up 1H‐MRSI were seizure‐free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H‐MRSI examination and follow‐up 1H‐MRSIs showed no significant difference (Z= 135, p = 0.893, 2‐tailed) for five seizure‐free patients.

Conclusions: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure‐free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.
Abnormal Wada and Neuropsychological Testing Results Due to Topiramate Therapy
Authors: McCabe Paul H. , Eslinger Paul J.
Published: August 2005

Summary: A 46‐year‐old man experienced intractable seizures since childhood. Due to lack of response to antiepilepsy drugs (AEDs), he underwent a surgical evaluation that was consistent with seizure onset in the left medial temporal lobe. While on topiramate and carbamazepine, his preoperative neuropsychological scores and sodium amytal (Wada) scores were low and may have excluded him from surgery. Repeat testing on lamotrigine and carbamazepine showed improvement in his scores, allowing him to undergo surgery. Physicians must therefore be cautious in evaluating such test scores while a patient is on topiramate.
The Ketogenic Diet Inhibits Epileptogenesis in EL Mice: A Genetic Model for Idiopathic Epilepsy
Authors: Todorova M. T. , Tandon P. , Madore R. A. , Stafstrom C. E. , Seyfried T. N.
Published: August 2005

Summary:Purpose: The ketogenic diet (KD) is a high‐fat, low‐carbohydrate and ‐protein diet that has been used to treat refractory seizures in children for more than 75 years. However, little is known about how the KD inhibits seizures or its effects on epileptogenesis. Several animal models of epilepsy have responded favorably to KD treatment, but the KD has not been studied in animals with a genetic predisposition to seizures. Here we studied the antiepileptogenic effect of the KD in EL mice, an animal model for human idiopathic epilepsy.

Methods: Young male EL mice (postnatal day 30) were randomly separated into two groups fed ad libitum with either the KD (treated, n = 21) or Agway chow (control, n = 19). The mice were weighed and tested for seizures once per week for a total of 10 weeks. The effects of the KD on plasma levels of ketone bodies and glucose were analyzed at several time points throughout the study. Associative learning was compared between treated and control animals using a water maze.

Results: KD treatment delayed seizure onset in young male EL mice by 1 month; however, seizure protection was transient, inasmuch as the treated and control mice experienced a similar number and intensity of seizures after 6 weeks on the diet. Plasma glucose levels and associative learning were similar in the treated and control groups, but the plasma β‐hydroxybutyrate levels were significantly higher in mice on the KD. The level of ketosis, however, was not predictive of seizure protection in EL mice.

Conclusion: The KD delayed seizure onset in EL mice, suggesting a transient protection against epileptogenesis. The KD did not influence plasma glucose levels or associative learning. Therefore, the EL mouse may serve as a good model to study the antiepileptogenic mechanisms of the KD.
The Clinical Usefulness of Ictal SPECT in Temporal Lobe Epilepsy: The Lateralization of Seizure Focus and Correlation with EEG
Authors: Lee Sang Kun , Lee Sung‐Hyn , Kim Seok‐Ki , Lee Dong‐Soo , Kim Ho
Published: August 2005

Summary: Purpose: To analyze the relationship between ictal electroencephalography (EEG) and ictal single‐photon emission computed tomography (SPECT) and to evaluate the diagnostic usefulness of ictal SPECT as an independent presurgical evaluation technique.

Methods: Sixty‐eight patients with temporal lobe epilepsy who underwent temporal lobectomy with good surgical outcome were included in this study. Ictal SPECT was performed during video‐EEG monitoring. The ictal EEG was analyzed in 5‐second intervals from the initiation of the ictal rhythm. Lateralized EEG dominance was determined by the amplitude, frequency, or regional patterns of ictal rhythm for each 5‐second interval. The total ictal EEG was divided into three periods: preinjection (maximum, 30 seconds), the initial part of the postinjection period (30 seconds), and the latter part of the postinjection period (30 to 60 seconds). The results of ictal SPECT were compared with the lateralized EEG dominance of each period and at seizure onset.

Results: Fifty‐four of 68 ictal EEGs correctly lateralized seizure focus ipsilateral to the side of surgery. Ictal SPECT correctly laterlized the epileptogenic temporal lobe in 61 of 68 patients (mean injection time, 29.8 seconds from onset). Multivariate analysis indicated that only the EEG dominance of the prejection period correlated significantly with the concordant hyperperfusion of ictal SPECT. Correct lateralization of ictal SPECT occurred in 10 of 14 patients with nonlateralized ictal EEG.

Conclusions: Preinjection neuronal activity seems to be important for the accurate interpretation of the hyperperfused patterns of ictal SPECT. Ictal SPECT is an independent and confirmatory presurgical evaluation technique.
Seizure Recurrence After a First Unprovoked Seizure in Childhood: A Prospective Study
Authors: Lizana J. Ramos , García E. Cassinello , Marina L. L. Carrasco , López M. Vázquez , Martín González M. , Hoyos A. Muñoz
Published: August 2005

Summary: Purpose: To study the risk of recurrence after a first unprovoked seizure in childhood.

Methods: All consecutive patients aged less than 14 years with one or more unprovoked seizures who were attended between January 1, 1987, and June 1, 1996, were included in a prospective study. Clinical features of patients attended after a first seizure and those attended after two or more seizures were compared. Recurrence risk in both groups was estimated by Kaplan‐Meier curves. Univariate and multivariate analyses of the potential predictors of recurrence risk were performed for the group of patients attended after a first seizure using the Cox proportional hazards model.

Results: Included in the study were 217 children. Kaplan‐Meier estimate of recurrence risk was 64% at 5 years, when only patients being attended after a first epileptic seizure were included, compared with 74% when all patients were included. Significant differences in several clinical features were found between patients attended after a first seizure and those attended after two or more seizures. Univariate and multivariate analyses showed that in the overall cohort of patients attended after a first seizure, a symptomatic etiology increased the risk of recurrence, whereas a patient age of 3 to 10 years decreased this risk. In particular, the recurrence risk was 96% at 2 years for symptomatic seizures, compared with 46% for idiopathic/cryptogenic seizures. In the group of patients with idiopathic/cryptogenic seizures, an abnormal electroencephalogram and the occurrence of seizures during sleep increased the recurrence risk, whereas a patient aged 3 to 10 years reduced it. In the group of patients with symptomatic etiology, univariate analysis revealed that there was a lower recurrence risk for patients aged 3 to 10 years. This last finding was not maintained, however, in multivariate analysis.

Conclusions: The recurrence risk depends on the inclusion criteria for enrolling patients. Several factors enable us to predict the recurrence risk after a first unprovoked seizure; the most important of these factors is the etiology of the seizures.
Enhancement of Progenitor Cell Division in the Dentate Gyrus Triggered by Initial Limbic Seizures in Rat Models of Epilepsy
Authors: Nakagawa Eiji , Aimi Yoshinari , Yasuhara Osamu , Tooyama Ikuo , Shimada Morimi , McGeer Patrick L. , Kimura Hiroshi
Published: August 2005

Summary: Purpose: Mitogenic effects of seizures on granule cell progenitors in the dentate gyrus were studied in two rat models of epilepsy. We investigated which stage of epileptogenesis is critical for eliciting progenitor cell division and whether seizure‐induced neuronal degeneration is responsible for the enhancement of progenitor cell division.

Methods: Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neurogenesis of dentate granule cells was evaluated using the bromodeoxyuridine (BrdU) labeling method, and neuronal degeneration was assessed by in situ DNA fragmentation analysis.

Results: After injection of KA, the number of BrdU‐positive granule cells began to increase at day 3 after the treatment, peaked at day 5, and returned to baseline at day 10. By day 13, the values were lower than control. After kindling, the number of BrdU‐positive cells began to increase after five consecutive experiences of stage I seizures. The increase occurred from day 1 to day 3 after the last electrical stimulation, but returned to baseline by day 7. After generalized seizures were well established, repeated stimulation did not facilitate division of granule cell progenitors. DNA fragmentation was noted in pyramidal neurons in the CA1, CA3, and hilus regions at 18 h after KA injection, but not in the kindling model.

Conclusions: These observations indicate that a mechanism in epileptogenesis boosts dentate progenitor cell division, but progenitor cells may become unreactive to prolonged generalized seizures. Pyramidal neuronal degeneration is not necessary for triggering the upregulation. It is suggested that newly born granule cells may play a role in the network reorganization that occurs during epileptogenesis.
Catastrophic Epilepsy in Childhood
Authors: Shields W. Donald
Published: August 2005

Summary: Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as “catastrophic” because the seizures are so difficult to control and because they are strongly associated with mental retardation. The catastrophic childhood epilepsies include uncommon disorders such as early infantile epileptic encephalopathy with suppression burst, severe myoclonic epilepsy of infancy, and epilepsy with myoclonic‐astatic seizures. There are other syndromes that are relatively common such as infantile spasms, Lennox‐Gastaut syndrome, and Sturge‐Weber syndrome. Many children with catastrophic epilepsy have the seizures as a result of underlying brain abnormalities that will inevitably lead to mental retardation whether or not they have seizures. In some patients, however, the mental retardation appears to be caused by the seizures. Developmental plasticity provides children with an opportunity to recover from significant brain injuries. However, the plasticity may also be the cause of the mental retardation. In such patients, control of the seizures may lead to more normal intellectual development. Thus, every effort should be made to control seizures in children with catastrophic epilepsy.
Characterization of Benzodiazepine Receptor Binding in Immature Rat Brain After Kainic Acid Administration
Authors: Rocha Luisa , González‐Trujano M. Eva , Jiménez Graciela , Gaona Andrés , Ondarza Rodolfo
Published: August 2005

Summary: Purpose: To evaluate the effects of status epilepticus on benzodiazepine (BDZ) receptor binding in immature rat brain.

Methods: Twenty‐four immature (15 days old) and six adult (90 days old) rats were used in this study. Status epilepticus was induced in immature animals by administration of kainic acid (7 mg/kg intraperitoneal), whereas adults rats received saline. Animals were killed 72 hours or 35 days after treatment, and their brains were used for in vitro autoradiography experiments to determine BDZ binding.

Results: In basal conditions and compared with the adult group, immature animals presented reduced BDZ binding in the entorhinal cortex, substantia nigra pars reticulata, and periaqueductal gray. Seventy‐two hours after kainic acid–induced status epilepticus, immature rats showed significantly increased BDZ in the frontal (48%), cingulate (39%), sensorimotor (39%), piriform (57%), and entorhinal (59%) cortices, the medial (84%) and basolateral (27%) amygdaloid nuclei, the dentate gyrus (51%), and the substantia nigra pars reticulata (43%). Thirty‐five days after status epilepticus, immature rats displayed decreased BDZ binding in the entorhinal cortex (48%), dentate gyrus (36%), and fields CA1, CA2, and CA3 of Ammon's horn (30%).

Conclusions: The present study demonstrates that status epilepticus and temporal lobe epilepsy produce a characteristic pattern of BDZ binding changes in the immature rat brain that differs from the one previously seen in adults.
Altered Receptor Subunit Expression in Rat Neocortical Malformations
Authors: Hablitz John J. , DeFazio R. Anthony
Published: August 2005

Summary: Purpose: Identification of changes in neurotransmitter function in animal models of epilepsy provides a basis for rational drug development and an understanding of the mechanisms underlying epileptogenesis. We investigated changes in the efficacy of the benzodiazepine type I agonist zolpidem and the polyamine site N‐methyl‐d‐aspartate receptor antagonist ifenprodil in a rat model of microgyria.

Methods: Neonatal freeze lesions were used to produce a microsulcus in the normally lissencephalic rat neocortex with anatomical similarities to human polymicrogyria. Whole‐cell voltage‐clamp recordings were made from visually identified layer 2/3 pyramidal cells in acutely prepared brain slices from nonlesioned and lesioned rats.

Results: The effect of 20 nmol/L zolpidem on the decay time constant of inhibitory postsynaptic currents was significantly less in neurons from brain slices containing the freeze lesion. A higher concentration (100 nmol/L) of zolpidem was equally efficacious in lesioned and nonlesioned cortex. In lesioned cortex, the threshold for evoking epileptiform discharges was significantly increased in the presence of 10 μmol/L ifenprodil. This effect was significant in both intrinsic hyperexcitability and partial disinhibition with 2 μmol/L bicuculline in lesioned cortex. Ifenprodil had significantly less effect on the threshold of discharges evoked in control cortex in the partial disinhibition model.

Conclusions: The decreased sensitivity of γ‐aminobutyric acid A receptors to 20 nmol/L zolpidem in the freeze‐lesion model is consistent with a delayed or arrested maturation in this animal model. These data support a delay in the developmental switch from α2 to α1 subunits in γ‐aminobutyric acid A receptors of neocortical pyramidal cells in lesioned cortex. The increased ifenprodil sensitivity of the threshold for evoking epileptiform discharges in both control and disinhibited slices containing the microsulcus is explained by a delay in the expression of the 2A (NR2A) N‐methyl‐d‐aspartate receptor subunit. Delayed development may be a hallmark of this type of cortical dysplasia.