bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsant Actions of Anticholinergic Drugs in Soman Poisoning
Authors: Capacio Benedict R. , Shih Tsung‐Ming
Published: November 2007

Summary: The acute effects of the organophosphorous cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, bi‐periden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman‐induced hypersecretions and convulsions. Male rats were injected with the oxime HI‐6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman (180 μg/kg, s.c; equivalent to 1.6 × the median lethal dose) that produced 100% convulsions. Signs of intoxication as well as the time‐to‐onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 μmol/kg for scopolamine HBr, biperiden, trihexyphenidyl, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order of potency for inhibition of hypersecretions among these compounds was observed. Parallel studies with quaternary analogs of atropine sulfate and scopolamine HBr demonstrated, however, that these charged compounds afford no protection against soman‐induced hypersecretions and convulsions. The results indicate that tertiary anticholinergic compounds afford protection against soman‐induced convulsions and hypersecretions and that the beneficial anticonvulsant effects are mediated through the central cholinergic system. Excitatory amino acid neurotransmitter systems may be involved in the effectiveness of these compounds.
Scalp and Limbic P3 Event‐Related Potentials in the Assessment of Patients with Temporal Lobe Epilepsy
Authors: Puce Aina , Bladin Peter F.
Published: November 2007

Summary: Auditory oddball scalp and limbic P3s were recorded from 18 patients with unilateral temporal lobe epilepsy (TLE) prior to seizure surgery. Limbic P3s were unilaterally absent ipsilateral to the seizure focus and were present in the nonepileptogenic temporal lobe in all 18 cases studied. Scalp P3s, recorded from C3 and C4, on the other hand, were elicited bilaterally and there was no significant difference in amplitude or latency between the epileptogenic and nonepileptogenic sides. These data concur with studies of scalp P3 performed following surgery and suggest that the assessment of the contribution of limbic P3 to scalp P3 may be masked by volume conduction effects and other generators of P3. We conclude that the P3 recorded from central scalp sites, unlike its limbic counterpart, offers little clinical information in the presurgical assessment of patients with TLE.
Magnetoencephalographic Localization of Subdural Dipoles in a Patient with Temporal Lobe Epilepsy
Authors: Rose Douglas F. , Sato Susumu , Ducla‐Soares Eduardo , Kufta Conrad V.
Published: November 2007

Summary: We report magnetoencephalographic localization of subdural electrode dipoles placed at the basal and mesial surfaces of the temporal lobe in a patient with temporal lobe epilepsy. The locations of the three dipoles were predicted from their magnetic fields with a computer model of the head as a conducting sphere. The predicted locations were within 1,3, and 4 mm of the actual locations. These results, obtained in an area of the brain from which epileptiform discharges are frequently recorded, strongly support the capability of magnetoencepha lography to accurately localize electrical events in this brain region.
Benign Partial Epilepsy of Childhood with Monomorphic Sharp Waves in Centrotemporal and Other Locations
Authors: Drury Ivo , Beydoun Ahmad
Published: November 2007

Summary: We reviewed EEGs from children whose history and clinical course was compatible with benign partial epilepsy of childhood with centrotemporal spikes. In 21% of patients with a single EEG focus, the discharge was outside the centrotemporal area. In 37.5% of patients with more than one focus, one was in the centrotemporal area while the other was not. We suggest that the typical EEG features of this syndrome are the normal background, the stereotypic morphology of the sharp waves, and their activation by drowsiness and sleep, not their exclusive location in the centrotemporal regions. Insistence on a centrotemporal location for the EEG discharges in this syndrome may lead to a misclassification of the type of epilepsy in some children with implications for therapeutic decisions and prognostic statements.
Outcome for West Syndrome Following Surgical Treatment
Authors: Uthman Basim M. , Reid S. A. , Wilder B. J. , Andriola M. R. , Beydoun Ahmad A.
Published: November 2007

Summary: We report the case of an 18‐month‐old child with infantile spasms and a hypsarrhythmic electroencephalogram (EEG) pattern associated with a porencephalic cyst. Surgical removal of the cyst and its surrounding tissue was performed following failure of medical therapy. Postoperatively, the patient has béen frée of infantile spasms for 12 months and the EEG has normalized. He has béen maintained on the same preoperative antiepileptic medications. This case suggests that surgical treatment is helpful in selected patients with infantile spasms and focal CNS lesions.
Epilepsy in Children with Mental Retardation: A Cohort Study
Authors: Goulden Keith J. , Shinnar Shlomo , Koller Helene , Katz Mindy , Richardson Stephen A.
Published: November 2007

Summary: The cumulative risk of seizures and epilepsy was investigated in a prospectively identified cohort of 221 children with mental retardation (MR) born between 1951 and 1955 in Aberdeen, Scotland. By age 22 years, 33 (15%) had epilepsy. An additional 16 (7%) had had at least one seizure, but did not meet the criteria for epilepsy. The cumulative risk of epilepsy was 9, 11, 13, and 15% at 5, 10, 15, and 22 years, respectively. In children with MR and no associated disabilities, the cumulative risk of epilepsy was only 2.6, 3.2, 3.9, and 5.2% at 5, 10, 15, and 22 years. In children with MR and cerebral palsy (CP), the cumulative risk was 28, 31, and 38% at 5, 10, and 22 years. Children with a postnatal injury associated with MR had a cumulative risk of epilepsy of 53, 66, and 66% at 5, 10, and 15 years after the injury. By age 22 years, 39% had achieved 5‐year seizure‐free remission, including 56% of children with MR without associated disability, 47% of children with MR and CP, and 11% of children with a postnatal injury. We conclude that, in the absence of associated disability or postnatal injury, the risk of epilepsy in the retarded population is low. Epilepsy in this population also will frequently enter remission in later life.
The Influence of Electroencephalographic Focus Laterality on Efficacy of Carbamazepine in Complex Partial and Secondarily Generalized Tonic‐Clonic Seizures
Authors: Defazio Giovanni , Lepore Vito , Specchio Luigi M. , Pisani Francesco , Livrea Paolo
Published: November 2007

Summary: Forty‐five outpatients with chronic epilepsy with complex partial seizures (CPS) alone or associated with secondarily generalized tonic‐clonic seizures (SGTCS) were treated with carbamazepine (CBZ) monotherapy. All patients had only a unilateral scalp electroencephalographic (EEG) focus. Left‐ (n = 29) and right‐(n = 16) sided foci patients were comparable for age, sex, duration, and etiology of epilepsy as well as total and free CBZ serum levels. CBZ significantly improved CPS irrespective of the side of the EEG focus, whereas SGTCS were controlled for >1 year in 15 of 19 patients with left focus and in three of 11 patients with right focus. When patients with poorly controlled seizures discontinued CBZ and changed to other therapies, they achieved a significant reduction in number of SGTCS, whereas the number of CPS was unchanged. The side of EEG focus seemed to be relevant to the control of SGTCS by CBZ. Interhemispheric neurotransmitter asymmetries may be involved in the EEG focus side‐dependent CBZ response.
Clinical Trials of Investigational Antiepileptic Drugs: Monotherapy Designs
Authors: Pledger Gordon W. , Kramer Lynn D.
Published: November 2007

Summary: The standard designs for safety and efficacy trials of investigational antiepileptic drugs are placebo‐controlled, add‐on trials and active control equivalence studies. These designs, motivated by medical ethics, have serious evidential limitations. Add‐on trials are frequently criticized as insensitive and difficult to interpret in the presence of drug interactions; active control equivalence studies are not probative of test drug activity. As an alternative, we describe two trial designs: a placebo‐control design with inpatients who in undergoing a presurgery seizure evaluation have had all antiepileptic drugs discontinued; and an active‐control design aimed at showing the test drug superior to the control treatment, thus avoiding the interpretational difficulties of no‐difference outcomes. A critical feature of these new designs is the limitation of subject exposure to unacceptable treatments. This is accomplished through protocol criteria–corresponding to therapeutic failure–which both terminate a subject's trial participation and form the basis of efficacy comparisons.
Relationship Between Platelet and Brain GABA Transaminase Inhibition by Single and Multiple Doses of Vigabatrin in Rats
Authors: Valdizán Elsa M. , Armijo Juan A.
Published: November 2007

Summary: Vigabatrin (‐γ‐vinyl‐GABA, GVG) is an inhibitor of brain GABA transaminase (GABA‐T) that also inhibits platelet GAB A‐T in rats and humans. We have compared the effects of single and multiple doses of GVG on both enzymes in 19 groups of 10 adult male Wistar rats, treated with increasing GVG doses (0–1,600 mg/kg/ day) for 1, 8, and 28 days. The platelet GABA‐T was more sensitive to the inhibitory effects of GVG than the brain enzyme was especially with low dosages of GVG. After 8 days of treatment, higher GVG plasma levels and a higher inhibition of both enzymes were shown. However, after 28 days, lower GVG plasma levels and similar inhibition of both enzymes compared to the eighth day were found. Correlations between platelet and brain GABA‐T for individual rats were statistically significant after 1 day (r= 0.40, p < 0.01) but not after 8 and 28 days of treatment because of the total inhibition of platelet GABA‐T and only partial inhibition of brain GABA‐T. We concluded the following: (a) platelet GABA‐T is more inhibited than brain GABA‐T when low doses of GVG are used and (b) multiple doses reach a higher inhibition of both enzymes than single doses, which could be explained by an increase in GVG concentrations.
Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio
Authors: Sakai S. , Baba H. , Sato M. , Wada J. A.
Published: November 2007

SUMMARY: The effect of DN‐1417, a thyrotropin‐releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4–5 days. A study of the transcallosal response also showed a long‐lasting attenuation of the early positive wave (PI) amplitude (peak latency, 5–10 ms) elicited by a single stimulus after cisternal injection of DN‐1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.

L'effet du DN‐1417, un analogue de la TRH, sur la photosensibilité et les crises après kindling cortical, a étéétudié chez sept babouins sénégalais Papio papio. L'administration intraveineuse de 2 mg/kg n'a pas eu d'effet, ni sur la photosensibilité, ni sur les crises après kindling cortical. Cependant, lorsque cet agent a été administré par voie intraventriculaire, la réponse photomyoclonique et les crises induites par kindling cortical ont été supprimées pendant 4 à 5 jours. Une étude de la réponse transcalleuse a également montré une atténuation prolongée de la pointe positive précoce (Iatence du pic, 5–10 ms) provoquée par une stimulation isolée après injection intracisternale de DN‐1417. Ces constatations confirment l'hypothèse selon laquelle la TRH endogène est impliquée dans la suppression des crises épileptiques.

En 7 babiones senegaleses Papio papio, se ha estudiado el efecto de la DN‐1417, un análogo de la hormona liberadora de tirotropina (TRH), sobre lafotosensibilidad de los ataques condi‐cionados corticalmente (kindled). La administración intravenosa de 2 mg/kg no produjo ningún efecto sobre la fotosensibilidad ni sobre los ataques condicionados corticalmente. Cuando este agente se administró intracistemalmente la respuesta fotomio‐clónica y los ataques condicionados corticalmente se suprimieron durante 4–5 días. Un estudio de la respuesta transcallosa también mostró una atenuación prolongada de la amplitud (latencia pico, 5–10 msec) producida por un estímulo único después de la inyección cisternal de DN‐1417. Estos hallazgos están de acuerdo con la presunción de que la TRH endógena participa en la supresión de ataques epilépticos.
Dreams and Epilepsy
Authors: Reami Denilce O. , Silva Délrio F. , Albuquerque Marly , Campos Carlos J. R.
Published: November 2007

SUMMARY: The relationship between dreams and epilepsy is illustrated by two patients whose awake epileptic seizures and recurrent dreams during night sleep had similar content. In both of our cases the EEG showed right anterior temporal spike discharge, suggesting a role for the temporal lobe in the association between dreams and seizures.

La relation entre les rêves et l'épilepsie est illustrée par deux observations dans lesquelles le contenu subjectif était le même lors des crises survenant à la veille et lors des rêves répétés au cours de la nuit. Dans les deux cas rapportés l'EEG a mis en évidence des décharges de pointes‐ondes temporales antérieures droites, ce qui suggère que le lobe temporal joue un rôle dans l'association entre rêves et crises.

La relación entre sueños y epilepsía se ilustra en dos casos en los que, durante los ataques epilépticos y los sueños recurrentes durante la noche, tenían un contenido semejante. En estos dos casos el EEG mostró un foco de descargas de puntas en la región temporal anterior derecha que sugiere la participación del lóbulo temporal como asociación entre sueños y ataques.

Die Beziehung zwischen Träumen und Epilepsie wird an zwei Fallbeispielen dargestellt, bei welchen ahnliche Inhalte er‐schienen, entweder bei Anfällen im Wachzustand oder Träumen im Schlaf. In unseren beiden Fällen zeigte das EEG rechts temporal vorne spike‐Entladungen, so daβ eine Beteiligung des Temporallappens gleichermaβen bei Träumen und bei Anfällen vermutet wird.
Overview of the Clinical Efficacy of Lamotrigine
Authors: Richens A. , Yuen A. W. C.
Published: November 2007

Summary: Testing the efficacy of lamotrigine (LTG) in epileptic patients has been approached in several ways. The first pilot study examined the effect of a single dose of LTG in patients with frequent interictal spikes, and a reduction in spike frequency was observed. Subsequently, single doses reduced photosensitivity in appropriate patients. Single‐blind administration of LTG for 1 week in addition to the patients' regular antiepileptic drugs (AEDs), in patients with refractory seizures, reduced seizures despite the short duration of therapy. This regimen was continued using a placebo‐controlled crossover study with 1‐week duration of treatment. Efficacy in partial and tonic‐clonic seizures was subsequently confirmed in four double‐blind crossover studies; a meta‐analysis of these four studies showed a 30% reduction in partial seizures despite the intractable nature of the seizures in the patients included. Current studies aim at evaluating the drug as monotherapy and in different seizure types.
Effect of Non‐Sex Hormones on Neuronal Excitability, Seizures, and the Electroencephalogram
Authors: Holmes Gregory L.
Published: November 2007

Summary: : Several of the non‐sex hormones have been found to be useful in the treatment of seizures. These hormones have an effect on seizures, and seizures have an effect on these hormones. Adrenocorticotropic hormone (ACTH) and corticosteroid drugs have been found to be useful in the treatment of infantile spasms and other seizure disorders. Unfortunately, there is no clear consensus regarding superiority of ACTH versus prednisone in regard to efficacy and long‐term benefits, dosage, or duration of treatment. There is also considerable debate regarding reasons why ACTH and prednisone are useful in infantile spasms, their mechanism of action, and their long‐term effects on brain development. Thyrotropin‐releasing hormone also has been used in the treatment of infantile spasms and other seizure types in children, with modest success. As with ACTH and prednisone, the mechanisms of action remain unclear.
The Effect of Seizures on Hormones
Authors: III Paul B. Pritchard
Published: November 2007

Summary: Serum prolactin (HPR) levels are influenced by waking and sleep states, as reflected by surges in serum concentrations during daytime naps and nocturnal sleep. Other physiological causes of hyperprolactinemia include sexual activity, pregnancy, and lactation. Drugs may stimulate or inhibit HPR secretion. Pathological causes for HPR secretion include destructive lesions of the hypothalamus, prolactin‐secreting neoplasms of the pituitary gland, lesions of the spinal cord, and occasionally Parkinson's disease. The most predictable postictal changes are increased serum Cortisol levels and hyperprolactinemia. Serum HPR rises after virtually all generalized tonic‐clonic seizures, most complex partial seizures, and some simple partial seizures. Absence and myoclonic seizures do not affect serum HPR levels. Repeated epileptic seizures and electroconvulsive therapy treatments produce successively less marked rises in serum HPR. The postictal elevation of serum Cortisol has a longer latency than for HPR and follows an earlier rise in serum ACTH. Other postictal hormonal changes are much more variable. Because of the normal diurnal variation in serum Cortisol levels and the relative delay in the postictal elevation of serum Cortisol, HPR is more useful as a diagnostic measure of epileptic seizures. This application of HPR requires an understanding of other factors that influence serum HPR and the use of baseline serum HPR levels for comparison. HPR data must be correlated with behavioral and electroencephalographic events.
Pregnancy and Epilepsy
Authors: Yerby Mark S.
Published: November 2007

Summary: : Women with epilepsy account for approximately 0.5% of all pregnancies. Their pregnancies are high risk because of an increased frequency of maternal seizures, complications of pregnancy, and adverse pregnancy outcomes. The increase in seizure frequency is associated with a progressive decline in antiepileptic drug (AED) levels during pregnancy even with constant dosing. Fetal deaths after a generalized seizure, although rare, have been reported, and a marked decline in fetal heart rate has been demonstrated after such seizures during delivery. AEDs have been implicated in causing a twofold increase in the rate of congenital malformations, a variety of minor physical anomalies, mostly involving the midface, and a neonatal hemorrhagic disorder. The clinician caring for a pregnant woman with epilepsy is therefore faced with a dilemma and must carefully chart a middle ground providing effective seizure control while minimizing fetal exposure to AEDs
Innovative Designs of Controlled Clinical Trials in Epilepsy
Authors: Gram Lennart , Schmidt Dieter
Published: November 2007

Summary: Uncontrolled noncomparative clinical observations of investigational antiepileptic drugs (AEDs) often lead to overoptimistic efficacy results and are therefore of very limited value for clinical AED development. The classic add‐on trial with placebo as control treatment, in contrast, has provided unequivocal evidence of the efficacy of classic and new AEDs and has also identified less useful AEDs. Drug interactions, carryover effects, difficulty in analyzing individual drug action, and the recognition that monotherapy is by far the more common way of prescribing AEDs have led to the development of classic active control monotherapy trials. A major problem of these trials is a no‐difference outcome, which allows no useful interpretation. Recently, two alternative monotherapy designs have been developed to avoid the deadlock of a no‐difference outcome. In these designs the active control drug is administered in an attenuated form (low dosage or low concentration) or a placebo control is used when standard treatment is discontinued during presurgical evaluation. Both designs have produced unequivocal evidence of the efficacy of the investigational AED during monotherapy. Ethical concerns are minimized by the introduction of preset escape criteria for patient protection. These designs are valuable new supplements for the clinical development of investigational AEDs for monotherapy in epilepsy. In our opinion, alternative monotherapy designs should be preceded by more than one pivotal add‐on, placebo‐controlled trial.
Felbamate in the Treatment of Lennox‐Gastaut Syndrome: Results of a 12‐Month Open‐Label Study Following a Randomized Clinical Trial
Authors: Dodson W. Edwin.
Published: November 2007

Summary: Felbamate (FBM) is a new antiepileptic drug (AED) that has been evaluated in partial seizures and in the Lennox‐Gastaut syndrome (LGS). When tested against placebo in an add‐on, randomized, double‐blind trial in 73 children with LGS, FBM significantly reduced the frequencies of astatic (atonic) seizures and generalized tonic‐clonic seizures plus total seizure counts. In addition, FBM‐treated subjects improved significantly on a parent‐rated global evaluation and had fewer injuries. Overall, ˜50% of subjects experienced a 50% or greater reduction in total seizure frequency and a dose‐response relationship was apparent. The improvement that occurred in the double‐blind study has been sustained for at least 12 months in subsequent open‐label follow‐up studies. In the first month of FBM treatment, 62% of the subjects who had previously received placebo had a reduction in total seizure frequency of >50%. By the 12‐month follow‐up point, approximately half of the patients had a 50% reduction in total seizure count. Astatic seizures responded even better, with two‐thirds of patients having a reduction of >50% in astatic seizure frequency after 12 months of treatment. Based on adverse experience reports thus far, FBM appears to be well tolerated. FBM is the first drug to be shown effective in the LGS in randomized controlled trials. Although few subjects with LGS became seizure free, the frequency of the most severe seizure types decreased and the patients' global functioning improved.
Convulsive Status Epilepticus in Children
Authors: Gross‐Tsur Varda , Shinnar Shlomo
Published: November 2007

Summary: Status epilepticus (SE) occurs most commonly in infancy and childhood. Children with prior neurological abnormalities are most susceptible. More than 90% of cases are convulsive and the majority are generalized. SE may occur in the setting of an acute illness, in patients with established epilepsy or as a first unprovoked seizure. The etiology can be classified as idiopathic, remote symptomatic, febrile, acute symptomatic, or associated with a progressive encephalopathy. The morbidity and mortality of status have dramatically declined in recent years. Overall mortality in recent pediatric series was 3–10%, with almost all fatalities associated with acute central nervous system insults or progressive neurologic disorders. Neurological sequelae in children with idiopathic or febrile status are rare. Neurologically normal children with SE as their first unprovoked seizure have the same risk of experiencing subsequent seizures of any type as children who present with a brief first seizure. The risk of recurrent episodes of convulsive SE approaches 50% in neurologically abnormal children but is very low in neurologically normal children. The favorable outcome of SE in children may be related to advances in therapy and to the resistance of the immature brain to damage from seizures.
Generalized Convulsive Status Epilepticus in the Adult
Authors: Treiman David M.
Published: November 2007

Summary: Status epilepticus (SE) is denned as recurrent epileptic seizures without full recovery of consciousness before the next seizure begins, or more‐or‐less continuous clinical and/or electrical seizure activity lasting for more than 30 min whether or not consciousness is impaired. Three presentations of SE are now recognized: recurrent generalized tonic and/or clonic seizures without full recovery of consciousness between attacks, nonconvulsive status where the patient appears to be in a prolonged “epileptic twilight state,” and continuous/repetitive focal seizure activity without alteration of consciousness. Generalized convulsive status epilepticus (GCSE) encompasses a broad spectrum of clinical presentations from repeated overt generalized tonic‐clonic seizures to subtle convulsive movements in a profoundly comatose patient. Thus, GCSE is a dynamic state that is characterized by paroxysmal or continuous tonic and/or clonic motor activity, which may be symmetrical or asymmetrical and overt or subtle but which is associated with a marked impairment of consciousness and with bilateral (although frequently asymmetrical) ictal discharges on the EEG. Just as there is a progression from overt to increasingly subtle clinical manifestations of GCSE, there is also a predictable sequence of progressive EEG changes during untreated GCSE. A sequence of five patterns of ictal discharges has been observed: discrete electrographic seizures, waxing and waning, continuous, continuous with flat periods, and periodic epileptiform discharges on a relatively flat background. A patient actively having seizures or comatose who exhibits any of these patterns on EEG should be considered to be in GCSE and should be treated aggressively to stop all clinical and electrical seizure activity to prevent further neurological morbidity and mortality.
Pathophysiological Mechanisms of Brain Damage from Status Epilepticus
Authors: Wasterlain Claude G. , Fujikawa Denson G. , Penix LaRoy , Sankar Raman
Published: November 2007

Summary: Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electrotonic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N‐methyl‐d‐aspartate (NMDA) and non‐NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
Epileptogenic Effects of Status Epilepticus
Authors: Lothman Eric W. , III Edward H. Bertram
Published: November 2007

Summary: Determining whether and under what conditions status epilepticus (SE) leads to undesirable long‐term sequelae has major clinical ramifications. In addition to structural brain damage and enduring neurological deficits following SE, it has been suggested that SE can establish a chronic condition of active epilepsy. These three residua (epileptic brain damage, neurological deficits, and epilepsy) have been especially linked to protracted SE. The older clinical literature indicates that these sequelae are especially likely if SE occurs in an immature brain, but this point has been challenged in recent studies. Clinical and animal model work that examines the issue of chronic nervous system deficits arising as a consequence of SE is reviewed, with particular attention to the question of the epileptogenic effect of SE. Because of the inherent problem of not being able to exclude occult neurological disease antecedent to SE in brain, animal model work promises to be especially relevant to the issues at hand. Work done on adult rats has shown that a previously normal brain can be “converted” after a bout of SE to an epileptic brain, as manifest both by epileptic brain damage resembling that found in the hippocampus of patients with intractable temporal lobe epilepsy and by spontaneous recurrent seizures registered in the hippocampus. A two‐step model is proposed: morphological brain injury takes place first and this change, in turn, promotes seizures. This model is offered as one way in which chronic active epilepsy can be established by a transient episode of SE. Although some findings from work with animal models have been interpreted as not supporting the idea that the immature brain is sensitive to a chronic epileptogenic influence initiated by SE, the majority of such work is consistent with this idea. On the other hand, a considerable amount of animal work indicates that the brains of immature animals are quite resistant to SE‐induced brain damage, in contrast to those of adults. Thus, under these circumstances, a different process of epileptogenesis than the two‐step model may be operational. It is concluded that, under appropriate conditions, SE does exert an epileptogenic effect that persists.
Treatment of Status Epilepticus
Authors: Ramsay R. Eugene
Published: November 2007

Summary:Status epilepticus, particularly the convulsive form, is a medical emergency, warranting prompt and aggressive treatment. To do this, one must have a thorough understanding of the pharmacology of the anticonvulsant agents. Therapy should be directed toward rapid termination of the status epilepticus, prevention of seizure recurrence, and treatment of any underlying cause. Most importantly, one should establish and adhere to a standard treatment protocol for best results.
Developing a Model of Quality of Life in Epilepsy: The Contribution of Neuropsychology
Authors: Hermann Bruce P.
Published: November 2007

Summary: Three specific issues must be considered in the development of a quality‐of‐life in epilepsy model and psychometric instrument. These issues are: (a) whether to adopt a narrow versus broad model of quality of life, (b) whether to rely on patient self‐reports of quality of life or reports garnered from proxies, and (c) whether to develop a generic versus disease‐specific measure of quality of life. In reviewing these issues the contributions of the health services research field, research pertaining to the psychological and social effects of epilepsy, and especially neuropsychology, are pertinent.
Research Use of the New Quality‐of‐Life in Epilepsy Inventory
Authors: Meador Kimford J.
Published: November 2007

Summary: Epilepsy is a heterogeneous disease with variable onset and prognosis. In general, patients with epilepsy have neuropsychological impairments. Their educational and occupational achievements may be lower than might be expected for their level of cognition. Some epilepsy patients suffer emotional distress, interictal behavioral disorders, and extreme social isolation. It is obvious that epilepsy and its sequelae impact on the patient's quality of life. What is not clear is the degree to which different factors contribute and the causes for extreme variance across patients. For example, the patients' perceptions of their disease affects quality of life more than actual seizure severity, but the mechanisms underlying this effect are not known. Quality‐of‐life research in epilepsy is in its infancy. In the future, such research will play an important role in assessing patient suffering, demonstrating the efficacy of treatments and interventions, and influencing medical economic decisions.
A Clinimetric Approach to Assessing Quality of Life in Epilepsy
Authors: Cramer Joyce A.
Published: November 2007

Summary: Clinimetrics is a concept involving the use of rating scales for clinical phenomena ranging from physical examinations to functional performance. Clinimetric or rating scales can be used for defining patient status and changes that occur during long‐term observation. The scores derived from such scales can be used as guidelines for intervention, treatment, or prediction of outcome. In epilepsy, clinimetric scales have been developed for assessing seizure frequency, seizure severity, adverse effects related to antiepileptic drugs (AEDs), and quality of life after surgery for epilepsy. The VA Epilepsy Cooperative Study seizure rating scale combines frequency and severity in a weighted scoring system for simple and complex partial and generalized tonic‐clonic seizures, summing all items in a total seizure score. Similarly, the rating scales for systemic toxicity and neurotoxicity use scores weighted for severity for assessing specific adverse effects typically related to AEDs. A composite score, obtained by adding the scores for seizures, systemic toxicity, and neurotoxicity, represents the overall status of the patient at a given time. The Chalfont Seizure Severity Scale also applies scores relative to the impact of a given item on the patient, without factoring in seizure frequency. The Liverpool Seizure Severity Scale is a patient questionnaire covering perceived seizure severity and the impact of ictal and postictal events. The UCLA Epilepsy Surgery Inventory (ESI‐55) assesses quality of life for patients who have undergone surgery for epilepsy using generic health status instruments with additional epilepsy‐specific items. The need is apparent for a single comprehensive instrument that assesses all aspects of epilepsy (e.g., effects of seizures and AEDs on patient medical status, psychosocial function, and quality of life). Quality‐of‐life assessment should come primarily from the patient, with ancillary material provided by family and health care providers. Only the patient can evaluate his or her current status vis‐à‐vis expectations. The balance between perceived and desired status is the essence of the quality‐of‐life equation.
Current Treatment Strategies in Selected Situations in Epilepsy
Authors: Treiman David M.
Published: November 2007

Summary: Several special situations in the management of epilepsy require specific treatment strategies. Recurrence rates after a single seizure vary between 26 and 71%. Antiepileptic drug (AED) therapy should be initiated after a first seizure only when a definitive diagnosis of epilepsy can be made. Although several AEDs have been shown to be antiepileptogenic in animal models, no data yet prove the efficacy of any AED in preventing the development of post‐traumatic or postoperative epilepsy. Therefore, there is no rational basis for prophylactic treatment with AEDs. The incidence of epilepsy rises dramatically after the age of 50 years. Simultaneously, many physiological changes increase the potential for adverse effects and drug interactions when AEDs are used in the elderly. Careful attention to changing pharmacokinetic parameters is necessary when that group of patients is being managed. Pregnancy also brings about physiological changes that may either increase or decrease the seizure frequency. The risk of fetal malformations is approximately double in children born to mothers with epilepsy compared with children born to nonepileptic mothers. The risk is dose‐dependent and increases with the number of AEDs. All AEDs may cause fetal malformations; valproate and carbamazepine increase the risk of spina bifida. Nonetheless, the best AED for a woman who wants to become pregnant is the AED that best controls her seizures, which should be given at the lowest possible effective dose. Discontinuation of AEDs can be considered after 2–4 years of complete seizure control. Most of the risk of relapse occurs within the first 6 months. Status epilepticus (SE) is a medical emergency. The most common form of SE is generalized convulsive status epilepticus, in which the patient may present with either overt or subtle convulsions. Because of the potential for neuronal damage, all electrical as well as clinical seizure activity must be completely stopped for treatment of SE to be considered successful.
Advances in the Pharmacotherapy of Epilepsy
Authors: Ramsay R. Eugene
Published: November 2007

Summary: Three new antiepileptic drugs (AEDs) are likely to be approved in the United States by the Food and Drug Administration in the near future. In general, all three have good safety profiles, causing only mild, well‐tolerated side effects. Felbamate (FBM) is effective in the treatment of partial seizures and Lennox‐Gastaut epilepsy. FBM appears to have a broader spectrum of antiepileptic activity than carbama‐zepine (CBZ) or phenytoin (PHT). Gabapentin (GBP) was designed to be a structured analogue of γ‐aminobutyric acid (GABA). GBP is most effective in the maximal electroshock model of seizures but may have a different mechanism of action than CBZ and PHT. Unique pharmacokinetic properties (no hepatic metabolism and no protein binding) may make GBP especially useful for certain patients, such as those with hepatic disease and elderly patients who are receiving multiple medications. The overall profile of activity of la‐motrigine (LTG) is similar to that of PHT and may act on voltage‐sensitive sodium channels to stabilize neuronal membranes. LTG is effective in partial seizures, and there is some indication that LTG may be helpful in primary generalized seizures. The long half‐life and lack of effect on other AEDs will make LTG easy to dose and add to a patient's existing regimen. These new agents will provide physicians with more effective medications from which to choose in the treatment of the patient with epilepsy.
Complex Genetic Disease: Can Genetic Strategies in Alzheimer's Disease and New Genetic Mechanisms Be Applied to Epilepsy?
Authors: Roses Allen D. , Pericak‐Vance Margaret A. , Saunders Ann M. , Schmechel Donald , Goldgaber Dmitry , Strittmatter Warren
Published: November 2007

Summary: Strategies used in molecular genetics have changed modern neurology. The gene or genes responsible for several major neurologic diseases have now been identified using “reverse” or positional genetics. Unexpected new genetic mechanisms have been discovered in human neurologic diseases, including (a) identical mutations of the prion protein gene in Creutzfeldt‐Jakob disease and fatal familial insomnia with the phenotypic expression directed by an accompanying polymorphism; (b) stable duplications of chromosome 17 in Charcot‐Marie‐Tooth disease (type 1 A) that involve many genes, only one of which appears to cause neuropathy; and (c) highly variable, dynamic mutations in myotonic dystrophy, fragile X syndrome, and Kennedy's syndrome that modulate variable expressivity in multiple tissues. There is growing recognition that neurologic diseases are often complex genetic diseases with multifactorial rather than simple modes of inheritance. For example, genetic association/linkage strategies have interacted with biochemistry and immunopathology studies to produce new insights into the disease mechanism of late‐onset Alzheimer's disease. The role of apolipoprotein E in late‐onset Alzheimer's disease is an example of how new analytical techniques of genetic disease can be applied to dissect multiple genes. Similar research strategies are suggested for the study of epilepsy as a complex disease.
Progress in Mapping Human Epilepsy Genes
Authors: Delgado‐Escueta Antonio V. , Serratosa Jose M. , Liu Amy , Weissbecker Karen , Medina Marco T. , Gee Manyee , Treiman Lucy J. , Sparkes Robert S.
Published: November 2007

Summary: The chromosomal loci for seven epilepsy genes have been identified in chromosomes lq, 6p, 8q, 16p, 20q, 21q, and 22q. In 1987, the first epilepsy locus was mapped in a common benign idiopathic generalized epilepsy syndrome, juvenile myoclonic epilepsy (JME). Properdin factor or Bf, human leukocyte antigen (HLA), and DNA markers in the HLA‐DQ region were genetically linked to JME and the locus, named EJM1, was assigned to the short arm of chromosome 6. Our latest studies, as well as those by White‐house et al., show that not all families with JME have their genetic locus in chromosome 6p, and that childhood absence epilepsy does not map to the same EJM1 locus. Recent results, therefore, favor genetic heterogeneity for JME and for the common idiopathic generalized epilepsies. Heterogeneity also exists in benign familial neonatal convulsions, a rare form of idiopathic generalized epilepsy. Two loci are now recognized; one in chromosome 20q (EBN1) and another in chromosome 8q. Heterogeneity also exists for the broad group of debilitating and often fatal progressive myoclonus epilepsies (PME). The gene locus (EPMI) for both the Baltic and Mediterranean types of PME or Unverricht‐Lundborg disease is the same and is located in the long arm of chromosome 21. Lafora type of PME does not map to the same EPMI locus in chromosome 21. PME can be caused by the juvenile type of Gaucher's disease, which maps to chromosome lq, by the juvenile type of neuronal ceroid lipofuscinoses (CLN3), which maps to chromosome 16p, and by the “cherry‐red‐spot‐myoclonus” syndrome of Guazzi or sialidosis type I, which has been localized to chromosome 10. A point mutation in the mitochondrial tRNALys coding gene can also cause PME in children and adults (MERFF).
Identification of Genetic Defect of an Epilepsy: Strategies for Therapeutic Advances
Authors: McNamara James O.
Published: November 2007

Summary: Advances in molecular genetics and molecular biology are transforming the biology of human disease. Cures for diseases previously refractory to all treatments have become the reality for some disorders and the legitimate promise for others. In the case of the epilepsies, identification of mutant genes underlying familial epilepsies may lead to a new pharmacology, through the development of in vitro expression systems permitting rapid search for novel drugs, creation of highly specific animal models based on expression of the precise mutation, and correction of disease phenotype by introducing novel and highly specific genetic information into the person with epilepsy.
Pharmacologic Intervention and Treatment of Childhood Seizure Disorders: Relative Efficacy and Safety of Antiepileptic Drugs
Authors: Bourgeois Blaise F. D.
Published: November 2007

Summary: : Four antiepileptic drugs (AEDs) represent > 90% of all AEDs prescribed in the United States. The efficacies of the available AEDs are surprisingly similar and far from complete, and none is entirely safe. Thus, the incidence of side effects is often the determining factor in the choice of AED. Clinical decisions about which AED to select should be made on the basis of the combination of efficacy and toxicity, expressed as a protective or therapeutic index (TI). Efficacy seldom comes without some degree of toxicity, whereas toxicity can occur in the absence of any efficacy. As the dose of the AED increases, efficacy can reach a plateau but toxicity does not. Complete seizure control should not be the final goal of epilepsy treatment; optimal AED therapy is equal to the highest possible TI, not necessarily to maximal seizure control. Each AED has a different TI, and each has a different TI in every patient. This is confounded further when combinations of AED are prescribed.
Investigational Antiepileptic Drugs for the Treatment of Childhood Seizure Disorders: A Review of Efficacy and Safety
Authors: Shields W. Donald
Published: November 2007

Summary: Pediatric epileptology is very different from adult epileptology. Although some epileptic disorders occur in both children and adults (e.g., localization‐related epilepsy with complex partial seizures and primary generalized epilepsy with tonic‐clonic seizures), other disorders can be called the catastrophic epilepsies of childhood (e.g., infantile spasms and the Lennox‐Gastaut syndrome). They occur, or at least begin, exclusively in childhood and are often associated with mental retardation. Many of these pediatric disorders are notoriously unresponsive to currently available antiepileptic drugs (AEDs). Although there are undoubtedly many reasons for this, one possible explanation is that the methods used to screen potential AEDs use animal models of adult epilepsy. No screening program uses an animal model of seizures that begin during development and lead to functional decline.
Prognosis of Childhood Seizure Disorders: Present and Future
Authors: Dreifuss Fritz E.
Published: November 2007

Summary: The prognoses for seizure disorders have been examined since the beginnings of epileptology, and only recently has the realization emerged that, ultimately, prognosis depends on causation, which, in turn, determines whether a condition is self‐limited or progressive. This factor is more important than either mode or alacrity of therapeutic intervention. The epilepsies are a series of conditions that have the final common path of either increasing cerebral irritability or synchronizing normally occurring electrical activity in such a manner that seizures result. In turn, some seizure disorders are characterized by secondary changes in neuronal synaptogenesis, leading to the development of circuits of predilection, which then render the process autonomous. Epilepto‐genesis has then become epilepsy, which is the norm in acquired rather than genetic epileptogenesis. An understanding of the basic differences between the primary (idiopathic) epilepsies and the secondary (acquired or symptomatic) epilepsies is basic to a discussion concerning prognosis and to the development of a definitive individualized treatment plan. An elucidation of the genetic factors in idiopathic epilepsy and their neurochemical consequences represents a major frontier in epileptology.