bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Anticonvulsant Activity of 4‐Chlorobenzenesulfonamide and Prototype Antiepileptic Drugs in Rodents
Authors: Clark C. Randall , McMillian Carl L.
Published: November 2007

Summary: The anticonvulsant and toxic properties of 4‐chlorobenzenesulfonamide (ADD SS0S1) were compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). These compounds were evaluated in mice and rats using well‐standardized anticonvulsant test procedures. The results indicate that ADD 55051 is a very effective anticonvulsant in the maximal electroshock seizure (MES) model in mice after either intraperitoneal (i.p.) or oral administration and in rats after oral administration. In mice treated i.p. or orally, ADD 55051 was also effective in preventing seizures induced by pentylenetetrazol (PTZ). The toxicity of ADD 55051 after oral administration was quite low, yielding high TD50 values in both mice and rats and producing a very high protective index (PI = TD50/ED50) in both species as compared with the prototype antiepileptic drugs (AEDs).

Las propiedades anticonvulsivas y tóxicas de la 4‐clorobenzen‐sulfonamida (ADD55051) ban sido comparadas con la fenitoina (OHT), fenobarbital (PB), etosuximida (ESM) y valproate (VPA). Estos compuestos han sido estudiados en ratones y ratas utilizando procedimientos anticonvulsives bien estandarizados. Los resulta‐dos indican que la ADD55051 es un anticonvulsive muy eficaz en ataques por electroschok máximo (MES) aplicado en ratones tras la inyección intraperitoneal (i.p.) o su administracion oral y en ratas tras su administracion oral. En los ratones tratados i.p u oralmente la ADD55051 tambieii fue eficaz en la prevenckta de ataques indu‐cidos por el pentilentetrazol (PTZ). La toxicidad de la ADD55051 tras la administracidn oral fue muy baja revelando valores elevados de TD 50 tanto en los ratones como en las ratas, produciendo un fndice muy elevado de protection (PI‐TD 50/ED50) en ambas espe‐cies comparandolos con prototipos de antiepilépticos.

Die antikonvulsiven und toxischen Eigenschaften von 4‐Chloro‐benzenesulfonamid (ADD 55051) wurde mit Phenytoin (PHT), Phe‐nobarbital (PB), Ethosuximid (ESM) und Valproat (VPA) veigti‐chen. Die Substanzen wurden bei Mäusen und Ratten in standard‐isierten Antikonvulsiva‐Tests untersucht. Die Ergebnisse zeigen, daβ ADD 55051 ein effektives Antikonvulsivum bei maximalen Elektroschockanfällen (MES) bei Mäusen sowohl bei interperito‐nealer (i.p.) oder oraler Applikation sind sowie bei Ratten nach oraler Applikation. Bei i.p. oder oral behandelten Mäusen war ADD 55051 auch zur Verhütung von Pentylenetetrazol‐Anfiälen wirksam. Die Toxizität von ADD 55051 nach oraler Applikation war recht niedrig mit TD50 Werten, die sowohl bei Mäusen als auch bei Ratten einen hohen Schutzindex (TO50/ED50) verglichen mit den bekannten Antiepileptika zeigten.
Antiepileptic Drug Treatment of Benign Childhood Epilepsy with Rolandic Spikes: Is It Necessary?
Authors: Ambrosetto Giovanni , Tassinari Carlo Alberto
Published: November 2007

Summary: Ten untreated and 20 treated patients with benign childhood epilepsy with rolandic (centrotemporal) spikes (BERS) were studied retrospectively after recovery. Seizure frequency, seizure recurrence, and duration of active epilepsy were similar in both groups. No differences were found in social adjustment. Antiepileptic treatment may be unnecessary in most cases of BERS.

Les auteurs ont étudié de façon rétrospective, après guérison, 10 patients non traités et 20 patients traités ayant présenté une épilepsie partielle bénigne de l'enfance à pointes centro‐temporales. La fréquence des crises, la récidive des crises et la durée de l'épilepsie active étaient les mêmes dans les deux groupes. Les auteurs n'ont pas constaté de différences dans le niveau d'ajustement social. Ces résultats suggérent qu'un traitement épileptique peut être superflu dans la plupart des cas d'épilepsie partielle bénigne a pointes centro‐temporales.

10 unbehandelte und 20 behandelte Patienten mit benigner Epilepsie im Kindesalter mit Rolando‐(zentro‐temporalen) spikes (BERS) wurden retrospektiv nach anhalten der Anfalls‐freiheit untersucht. Anfallshäufigkeit, Anfallsintervall und Dauer der aktiven Epilepsie waren bei beiden Gruppen ähnlich. Im Be‐reich der sozialen Anpassung fanden sich keine Unterschiede. Möglicherweise ist somit eine antiepileptische Behandlung der meisten Fälle mit BERS unnötig.
Anatomical, Physiological, and Theoretical Basis for the Antiepileptic Effect of Vagus Nerve Stimulation
Authors: Rutecki Paul
Published: November 2007

Summary: The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well‐defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalo‐graphic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desynchronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of ≤ 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3‐mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function.
Surgical Technique for Implantation of the Neurocybernetic Prosthesis
Authors: Reid Steven A.
Published: November 2007

Summary: The surgical technique for the implantation of the neurocybernetic prosthesis is described in detail. This procedure is straightforward and is easily carried out by surgeons familiar with carotid surgery.
Prevention of Intractable Partial Seizures by Intermittent Vagal Stimulation in Humans: Preliminary Results
Authors: Penry J. Kiffin , Dean J. Christine
Published: November 2007

Summary: Intermittent stimulation of the vagus nerve in four patients resulted in complete seizure control in two, a 40% reduction of seizure frequency in one, and no change in seizure frequency in the other. Side effects (hoarseness, stimulation sensation in the neck, and hiccups) were transient and occurred concomitantly with stimulation. All patients tolerated increasing stimulation parameters well. The results, however, are inconclusive because of the brief duration (6–12 months) of follow‐up. Vagal stimulation represents a novel approach for seizure control in patients who have intractable epilepsy, but additional studies are needed to clarify the efficacy and safety of the procedure and to define selection criteria for patients.
Chaos, Balance, and Development: Thoughts on Selected Childhood Epilepsy Syndromes
Authors: Vining Eileen P. G.
Published: November 2007

Summary: Age‐specific epilepsy syndromes raise important questions about developmental susceptibility to seizures and epileptogenesis and about the effect of seizures on function. The diagnosis and treatment of these syndromes has been enhanced by the use of modern science and technology. Epidemiologic studies have changed our approach to febrile convulsions. This developmental seizure disorder is benign and self‐limited. We have been forced to think carefully about threshold, therapy, and whether other seizures in childhood may be equally benign. This framework of developmental specificity can also be applied to West syndrome, especially with respect to neurophysiology, neurochemistry, neuroimaging, and epidemiology–the types of seizures, clustering, variations associated with sleep, PET scans, and therapy. Rasmussen's syndrome and other unilateral developmental epilepsies are progressive but remain confined to a single hemisphere. However, they usually are devastating to global neurologic function. They are models for examining the impact of epilepsy in one pathologic hemisphere on the function of the entire brain. Current therapy for this condition is hemispherectomy. Recovery of function after this major surgery is striking and provides clues to brain organization. The analysis of these three syndromes provides windows on the dynamic, changing central nervous system of the child and may lead to better understanding and therapy for other seizure disorders.
Epilepsy and Brain Tumors: Implications for Treatment
Authors: Cascino Gregory D.
Published: November 2007

Summary: Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low‐grade gliomas may be associated with a long‐standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure‐free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep‐seated lesions or involve functional cerebral cortex. Computer‐assisted stereotactic surgical procedures have been developed for biopsy and resection of intra‐axial brain‐mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.
Mesial Temporal Sclerosis: Pathogenesis, Diagnosis, and Management
Authors: Gates John R. , Cruz‐Rodriguez Raul
Published: November 2007

Summary: Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity–alone or mixed with other pathologic features–for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure‐free have tightly localized interictal abnormalities restricted to F7/F8, Spl/Sp2, T3/T4, and T5/T6 more than 96% of the time.

MRI abnormalities may be seen in 55% of patients with MTS if both “hard” and “soft” criteria are used or in 20% when only “hard” criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateral‐izing and localizing preoperative information.
Learning Disabilities in Epilepsy: Neurophysiological Aspects
Authors: Binnie C. D. , Channon S. , Marston D.
Published: November 2007

Summary: Subclinical generalized spike‐wave discharges are often accompanied by transitory cognitive impairment, demonstrable by psychological testing during EEG recording. Transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike‐wave bursts lasting for more than 3 s, but can also be found during briefer and even focal discharges. That this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity: left‐sided focal spiking is more likely to produce errors on verbal tasks, for instance, whereas right‐sided discharges are more often accompanied by impairment in handling nonverbal material. Both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges. However, there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities. The significance of transitory cognitive impairment accompanying subclinical EEG discharges for everyday functioning is uncertain, but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists. In some individuals, suppression of discharges by antiepileptic drugs has demonstrably improved psychological function, but further work is required to determine the indications for such treatment
Children with Epilepsy: The Effect of Seizures, Syndromes, and Etiological Factors on Cognitive Functioning
Authors: Dam M.
Published: November 2007

Summary:Overall, children with epilepsy have poorer concentration and mental processing and are less alert than age‐matched controls. The relationship between cognitive functioning and epilepsy is complex, however, with widely differing degrees of intellectual impairment–ranging from minimal to severe and progressive–related to diverse types of epileptic seizures, syndromes, and etiological factors. Prolonged and frequently repeated seizures are typically associated with more severe effects on cognitive functioning, particularly if epilepsy is symptomatic, i.e., secondary to a demonstrable brain lesion. A combination of such factors may contribute to the mental deterioration seen in many children suffering from severe epilepsy.
Discontinuation of Antiepileptic Drugs in Children Who Have Outgrown Epilepsy: Effects on Cognitive Function
Authors: Blennow G. , Heijbel J. , Sandstedt P. , Tonnby B.
Published: November 2007

Summary: Cognitive function is frequently impaired in children with epilepsy, compared with age‐matched controls. It can be hard to evaluate the significance of various contributory factors. The effects of antiepileptic drugs may be studied in children who have outgrown their epilepsy but are still being treated. A multicenter study to assess various aspects of cognitive function in children with different forms of epilepsy, both during and after treatment with antiepileptic drugs, is currently under way. Definitive results are not yet available; interim analysis of the findings suggests that short‐term memory is decreased in all subgroups of children being treated for epilepsy, compared to controls.
Cognitive Deficits in Children: Adaptive Behavior and Treatment Techniques
Authors: Strang J. D.
Published: November 2007

Summary: Impaired cognitive functioning impedes the development of age‐appropriate adaptive behavior, thus adding to the burdens of many children with epilepsy. Detailed neuropsychological assessment can identify the underlying ability‐related impairments that contribute to the adaptive behavior deficiencies evidenced, particularly in the home and school settings. This information can serve as the basis for a multidisciplinary treatment plan tailored to individual needs. Ideally, the need for such a treatment plan should be perceived early in childhood, so that it can be developed and applied preventively. The same remedial principles also apply in older children and are here set out in detail.
Fatal Hepatocerebral Syndrome in Siblings Discordant for Exposure to Valproate
Authors: Lenn Nicholas J. , Ellis William G. , Washburn Earl R. , Ruebner Boris
Published: November 2007

Summary: Occurrence of a progressive encephalopathy with seizures in siblings was associated with hepatic pathology. One of these patients was exposed to valproate (VPA) and developed hepatic necrosis, confirmed at autopsy. The other had not been exposed to VPA, and her hepatic lesions at autopsy were less severe. The liver pathology in both was within the range described in previous cases of liver disease attributed to VPA. These facts and the otherwise similar course of their disease suggests that in these patients, and probably in other cases of fatal liver failure attributed to VPA, the drug actually either had no effect or acted only to increase the severity of the preexisting hepatic component of the hepatocerebral disorder.

La survenue d'une encéphalopathie progressive s'accompagnant de crises dans une fratrie s'associait à une atteinte hépatique. L'un des patients a été exposé au valproate (VPA) et a présenté une nécrose hépatique qui a été confirmée par l'autopsie. L'autre patient n'a pas été exposé au valproate et les lésions hépatiques à l'autopsie ont été moins sévères. Dans le deux cas, l'examen anatomo‐pathologique du foie était compatible avec les cas antérieurement publiés d'hépatopathies liées au valproate. Ces faits, et l'évolution par ailleurs semblable de leurs maladies, suggèrent que dans ces cas, ainsi que probablement dans d'autres cas d'insuffisance hépatique fatale attribuée au VPA, le médicament en lui‐même n'a eu soit aucun effet, soit seulement un effet d'aggravation sur la composante hépatique existante de la maladie hépato‐cérébrale.

La aparición de una encefalopatía progresiva con ataques en hermanos se ha asociado a la presencia de patología hepática. Unos de nuestros enfermos fue tratado con ácido valproico (VPA) y desarrolló una necrosis hepática confirmada en autopsia. En el otro que, no había sido tratado con VPA, las lesiones hepáticas en autopsia fueron menos severas. La patología hepática en ambos puede bien incluirse dentro del contenido de enfermedad hepática previamente descrita en casos que habían tomado VPA. Estos datos y la semejanza de la evolución clímica de esta enfermedad, sugiere que, en los casos descritos y, probablemente, en otros en los que la lesión hepática fatal fue atribuida al VPA, la droga, o no produjo ningún efecto o simplemente actuó para incrementar la severidad de los componentes hepáticos preexistentes dentro del transtorno hepato‐cerebral.
Effects of Removal of Phenytoin, Carbamazepine, and Valproate on Cognitive Function
Authors: Duncan John S. , Shorvon Simon D. , Trimble Michael R.
Published: November 2007

Summary: Changes in cognitive function were noted in a double‐blind, prospective, placebo‐controlled study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 58 patients with active epilepsy, receiving multiple antiepileptic drugs (AEDs). A control group of 25 patients continued with existing therapy. A simple test battery, which would be directly applicable to a clinical setting, with measures of mental speed, attention, performance of a learned skill, shortterm memory, concentration, and simple coordinated hand movements was used. Cognitive assessments were made before and at the end of discontinuation of a drug and 4 weeks later. Simple motor skills became faster on discontinuation of PHT, CBZ, and VPA (p < 0.0005), with a further improvement in the subsequent 4 weeks (p = 0.03) and no significant difference between the AEDs. Performance on a measure of attention and concentration improved on discontinuation of PHT (p = 0.005) and did not alter with removal of CBZ or VPA; the improvement in the PHT discontinuation group was significantly different from that in the control group (p = 0.001). These results suggest that all three AEDs studied may adversely affect motor function and that PHT may be more deleterious to function in higher cognitive tasks than is CBZ or VPA.

Les auteurs ont étudié les modifications des fonctions cognitives relevées lors d'une étude prospective, en double‐aveugle, contrôlées contre placebo, de l'arrêt de la phénytoine (PHT), de la carbamazépine (CBZ) et du valproate (VPA) chez 58 patients présentant une épilepsie active, traités par une polythérapie. Un groupe contrôle de 25 patients a été maintenu sous le traitement antérieur. Une simple batterie de tests, tout à fait transférable à une situation clinique habituelle, a permis de mesurer la rapidité mentale, l'attention, la réalisation d'une tâche apprise, la mémoire à court terme, la concentration, et les mouvements simples des mains. L'évaluation cognitive a été effectuée avant et à la fin de l'arrêt du médicament, ainsi que 4 semaines plus tard. Les performances motrices simples sont devenues plus rapides après arrêt de PHT, CBZ et valproate (p < 0.0005), avec une amélioration encore accentuée pendant les 4 semaines suivantes (p = 0.03), sans qu'il y ait eu de différences significatives entre les différentes drogues. Les performances d'attention et de concentration ont été améliorées après arrêt de la PHT (p = 0.005), mais n'ont pas été modifiées après l'arrêt de CBZ ou de VPA; l'amélioration du groupe d'arrêt de la phénytoine a évé significativement différente de celle du groupe contrôle (p = 0.001). Ces résultats suggèrent que les 3 antiépileptiques étudiés peuvent retentir sur la fonction motrice, et que la PHT peut Être plus nocive sur les fonctions cognitives supérieures que la CBZ ou le VPA.
Epileptogenic Activity of Two Peptides Derived from Diazepam Binding Inhibitor After Intrahippocampal Injection in Rats
Authors: Vezzani A. , Serafini R. , Stasi M. A. , Samanin R. , Ferrarese C.
Published: November 2007

Summary: Peptides DBI 42–50 (DRPGLLDLK) and DBI 43–50 (RPGLLDLK) are synthetic fragments of an 18 amino acid peptide called octadecaneuropeptide (QATV‐GDVNTDRPGLLDLK), a brain derivative of diazepam‐binding inhibitor (DBI). The two peptides were unilaterally injected into the dorsal hippocampus (granule cells of dentate gyrus) of freely moving adult rats. The electroen‐cephalographic (EEG) pattern was continuously recorded from bilateral hippocampal and cortical electrodes, and the animals' behavior was observed throughout the experiment. A dose of 100 nmol peptide 42–50 was required to reliably cause EEG alterations (seizures and spiking). EEG changes, defined as seizures, were characterized by discrete repetitive periods of high‐frequency and/or mul‐tispike complexes and/or high‐voltage synchronized spike or wave activity. EEG seizures were often associated with a frozen appearance of the animal and “wet dog shakes.” Tonic‐clonic convulsions were not observed. EEG seizures induced by peptide 42–50 were prevented by 90 mg/kg PK 11195, a selective antagonist of a novel GABAA receptor‐linked subtype of a benzodiazepine (BDZ) receptor, but were unaffected by flumazenil, an agonist of the “central” type of BDZ receptor and by D(‐)2‐amino‐7‐phosphonoheptanoic acid, a selective antagonist of the N‐methyl‐D‐aspartate subtype of excitatory amino acid receptors. Light microscopy showed no neuropathological changes in the injected hippocampus. The data show that these DBI‐derived peptide fragments induce a typical pattern of limbic seizures in rats. DBI and/or its natural processing products may play a role in the pathophysiology of epilepsy.
Seizure Frequency in Intractable Partial Epilepsy: A Statistical Analysis
Authors: Balish Marshall , Albert Paul S. , Theodore William H.
Published: November 2007

Summary: We examined the seizure records of 13 patients (nine men and four women, ages 27–50 years) with intractable partial epilepsy, maintained with steady anti‐epileptic drug dosages. Patients recorded daily seizure frequency on calendars. Periods of outpatient observation ranged from 99 to 1,710 days and the number of observed seizures ranged from 18 to over 400, with daily seizure rates of 0.1–4.3 per day. We used the quasi‐likelihood regression model to examine the following four departures of the daily seizure counts from a Poisson (random) model: (1) linear increasing or decreasing time trends in expected seizure rates; (2) clustering, where the expected seizure rate on a given day depends on the number of seizures observed on the immediate prior days; (3) monthly cyclicity; and (4) increased variability (overdis‐persion). Linear time trends were seen in six patients (four increasing and two decreasing), clustering was seen in 10 patients, and a near‐monthly cycle appeared in four patients (two of nine men and two of four women). A significant amount of extra variation (overdispersion) relative to a Poisson distribution was observed in all but one of the 13 patients. Departures from a Poisson (random) model appear more common in this population of patients with medically intractable epilepsy than is commonly recognized, and have clinical importance as well as implications for the design of clinical studies.
Eye Closure Sensitivity Without Photosensitivity in Juvenile Myoclonic Epilepsy: Polysomnographic Study of Electroencephalographic Epileptiform Discharge Rates
Authors: Gigli G. L. , Calia E. , Luciani L. , Diomedi M. , Pierre L. De La , Marciani M. G. , Sasanelli F.
Published: November 2007

Summary: Two cases of juvenile myoclonic epilepsy (JME) presented with myoclonic jerks and EEG activation after eye closure, without sensitivity to intermittent photic stimulation. The effect of eye closure was computed by comparing discharge rates of polyspike‐and‐wave (PSW) complexes after eye closure and after eye opening. For one patient, never treated pharmacologically, a nocturnal polysomnograph was performed to study the variation of discharge rates of PSW complexes during wakefulness and sleep. The rate of PSW complexes was high during wakefulness before sleep onset, increased during spontaneous nocturnal awakenings, and became maximal during final morning awakening. Among nonrapid eye movement (NREM) sleep stages, EEG epileptiform activity was maximal during stages III and IV. Discharges were completely suppressed by rapid eye movement (REM) sleep. Awakenings following deep NREM sleep were very activating if no REM sleep was interposed. Awakenings from light NREM sleep were much less activating. There were no EEG abnormalities in awakenings immediately following REM sleep. Results suggest that REM sleep, similarly to eye opening, plays a role in inhibiting EEG manifestations of JME with eye closure sensitivity.
Recognition Impairment Correlated with Short Bisynchronous Epileptic Discharges
Authors: Provinciali Leandro , Signorino Mario , Censori Bruno , Ceravolo Gabriella , Pesce Maria Del
Published: November 2007

Summary: The occurrence of transitory cognitive impairment during diffuse subclinical electroencephalographic (EEG) discharges has been widely documented but the role of the parameters influencing the cognitive performance and the involvement of motor or verbal response in the tasks used is still under debate. Fifteen patients suffering from primary generalized epilepsy with frequent bisynchronous EEG epileptic bursts underwent a shape recognition task during EEG monitoring. The test sequence was as follows: memorandum, pause, and multiple choice set. After pressing the response button, the patient was asked to confirm the choice verbally. The following parameters were considered: geometrical complexity of the shape, chronological position of the burst occurring during the single test, and the duration of discharge ranging from 1 to 3 s. Results showed a significant increase in incorrect responses during the test when discharges occurred, with more errors occurring for difficult than for easy shapes. Neither the discharge position nor the duration of the epileptic burst influenced the performance. Diffuse epileptic activity of short duration produced selective effects on the cognitive process regardless of the motor component of the response.
Disability Pensions for Epilepsy With or Without Mental Retardation: A 15‐Year Swedish Survey
Authors: Silfvenius H. , Olivecrona M. , Forsgren L. , Backstrom L.
Published: November 2007

Summary: The disability pensions of the Swedish National Social Insurance Board to persons with epilepsy from January 1, 1971 to December 31, 1985 were studied. On the latter date 6,658 individuals in the register were receiving disability pensions. This corresponds to an age‐specific prevalence (16–64 years) of 1.2 per 1,000. Female and male patients were about equally represented. Four diagnostic categories were specified: I: 34% with epilepsy as the main diagnosis; II: 43% with epilepsy as a complementary diagnosis; III: 4% with epilepsy as a main and mental retardation (MR) as a complementary diagnosis; and IV: 19% with MR as a main and epilepsy as a complementary diagnosis. Overall 43% had both epilepsy and MR. The crude prevalence per county ranged from 0.25 to 1.23 per 1,000. Age on entry was 1.8–63.8 (mean, 36.7) years, and pension duration was 0.1–15 (mean, 7.4) years. Mean age on prevalence day was 43.9 years. During the 15‐year period annual pension costs were 20–380 million Swedish kronor (SEK) ($3–60 million), and the total costs were 2,370 million SEK ($365 million). Adjusted to 1989, the costs would be 84–463 million SEK ($13–71 million) and 4,258 million SEK ($655 million), respectively.
Treatment of Porphyric Convulsions with Magnesium Sulfate
Authors: Sadeh M. , Blatt I. , Martonovits G. , Karni A. , Goldhammer Y.
Published: November 2007

Summary: We report a 16‐year‐old girl with acute intermittent porphyria who had abdominal pain, generalized tonic‐clonic and simple partial seizures, and inappropriate antidiuretic hormone secretion. Because most antiepileptic drugs are contraindicated in porphyria, she was treated with magnesium sulfate i.v. Soon after starting treatment, seizures stopped, returned, and then again responded in several trials with discontinuation and reinstitution of i.v. magnesium sulfate. Our experience encourages the use of magnesium sulfate for treatment of seizures in patients with porphyria.
Lack of Major Effects on Mouse Brain Adenosine A1 Receptors of Oral Carbamazepine and Calcium Antagonists
Authors: Larkin John G. , Thompson George G. , Scobie Gordon , Drennan Joan E. , Brodie Martin J.
Published: November 2007

Summary: Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p < 0.005) and NMD (p < 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p < 0.05). These minor effects on A, receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.
Gaze‐Evoked Visual Seizures in Nonketotic Hyperglycemia
Authors: Duncan Max B. , Jabbari Bahman , Rosenberg Michael L.
Published: November 2007

Summary: Focal motor seizures are commonly a symptom of nonketotic hyperglycemia (NKH). Posture‐induced motor seizures are less common but have been reported in some patients with this disorder. We report the first case of gaze‐evoked sensory (visual) seizures in nonketotic hyperglycemia. Both seizures and ictal ÉEG findings disappeared shortly after hyperglycemia was corrected.

Des crises motrices focales sont un symptôme fréquent de l'hyperglycémie non cétosique. Des crises motrices induites par la posture sont moins fréquentes et ont été rapportées chez quelques patients présentant cette affection. Les auteurs rapportent le premier cas de crises sensorielles (visuelles) provoquées par la fixation dans le cadre d'une hyperglycémic non cétosique. Les crises et les constatations ÉEG critiques ont disparu rapidement après correction de l'hyperglycémie.

Ein Symptom der nicht‐ketotischen Hyperglykämie sind gewöhnlich fokal‐motorische Anfälle. Haltungsinduzierte motorische Anfälle sind weniger häufig, wurden jedoch bei einigen Patienten mit dieser Erkrankung berichtet. Wir berichten über den ersten Fall von durch Starren hervorgerufenen, sensorischen (visuellen) Anfällen bei nichtketotischer Hyperglykämie. Sowohl Anfälle als auch iktale ÉEG‐Befunde verschwanden kurz nach Besserung der Hyperglykämie.
Seizure‐Induced Protein Tyrosine Phosphorylation in Rat Brain Regions
Authors: Jope Richard S. , Johnson Gail V. W. , Baird M. Shane
Published: November 2007

Summary: Phosphorylation of protein tyrosines is an important modulatory process for cell signaling and other cellular functions. Rat brain regions were examined for altered protein phosphotyrosines, using Western blot analysis and microwave irradiation to limit postmortem alterations, after administration of two convulsants: lithium plus pilocarpine or kainic acid (KA). Most phospho‐tyrosine proteins were unaltered by these treatments, but there was a large, specific increase in the tyrosine phosphorylation of a 40‐Kd protein. This increase was evident in all three regions examined: cerebral cortex, hippocampus, and striatum; it occurred abruptly with onset of generalized status epilepticus (SE) and remained elevated for at least 90 min. Most of the tyrosine phosphorylated 40‐Kd protein was in the cytosolic fraction. These results demonstrate a large, specific effect of chemically induced seizures on a single phosphotyrosine protein in rat brain.

La phosphorylation des tyrosines protéiques est un processus de modulation important pour la communication intercellulaire et d'autres fonctions cellulaires. Des régions cérébrales de rat ont été examinées a la recherche de modification de phosphoty‐rosines protéiques, au moyen d'une analyse de type Western blot et d'une irradiation par micro‐ondes afin de limiter les altérations post‐mortem, aprés administration de 2 produits convulsivants, lithium + pilocarpine ou acide kainique. La plupart des protéines avec phosphotyrosines n'étaient pas modifées par ces traitements, les auteurs ont constaté une augmentation importante, spécifique de la phosphorylation de la tyrosine dans une protéine 40 kD. Cette élévation a été mise en eAvidence au niveau des 3 régions cérébrates examinées, le cortex cérébral, ľhippo‐campe et le striatum. Cette augmentation s'est produite de façon brutale au moment de la mise en place d'un état de mal généralisé, ľéiévation s'est maintenue pendant au moins 90 mn. La majorité de la protéine 40 kD avec tyrosine phosphoryiée a été trouvée au niveau de la fraction cytosolique. Ces résultats démontrent un effet important, spécifique des crises induites par convulsivants chimiques, sur une protéine particuliére du cerveau du rat.
Chronic, Habitual Cocaine Abuse and Kindling‐Induced Epilepsy: A Case Report
Authors: Dhuna Anil , Pascual‐Leone Alvaro , Langendorf Frederick
Published: November 2007

Summary: Kindling has been suggested as a possible mechanism for cocaine‐induced seizures in chronic cocaine abusers, even though no convincing examples have been reported. We report a 37‐year‐old woman who initially experienced generalized tonic‐clonic seizures (GTC) only immediately after “crack” use. She had a normal examination, negative family or past history for seizures, and normal cranial computed tomography and EEG. After she had abused cocaine almost daily for 2 years, her EEG demonstrated bitemporal slowing with independent spikes, and seizures were no longer temporally associated with acute cocaine use. Thereafter, despite complete abstinence from cocaine and treatment with phenytoin, she continued to experience four to six GTC a month. In light of the lack of other predisposing factors for epilepsy, this case may represent an example of cocaine‐induced kindling in humans.

A pesar de que no se han publicado ejemplos convincentes se ha sugerido que un proceso de condicionamiento (kindling) po‐dría ser el mecanismo de los ataques inducidos por la cocaina en adictos a esta droga. Publicamos una mujer de 37 años que, inicialmente, experimentó ataques generalizados tónico‐clónicos (GTC) solo inmediatamente después de usar “crack.” La exploratión clinica era normal y la historia familiar o personal negativa para ataques con un CT y un EEG normales. Tras 2 años de abuso casi diario de cocaina el EEG demostró una lentificación bitemporal con puntas independientes en el EEG. Los ataques ya no se asociaban temporalmente al uso agudo de cocaina. Después, y a pesar de una abstinencia completa y con un trat‐amiento con fenitoina, continuó con 4–6 GTC al mes. Al no existir otros factores que predisponen a padecer epilepsía, este caso puede representar un ejemplo de “kindling” (condicionamiento) por cocaina en humanos.
Reflex Epilepsy Induced by Calculation Using a “Soroban,” a Japanese Traditional Calculator
Authors: Yamamoto Junji , Egawa Isao , Yamamoto Shinobu , Shimizu Akira
Published: November 2007

SUMMARY: We report three cases of reflex epilepsy with myoclonic jerks of the right arm and fingers precipitated by calculation using a Soroban, An EEG spike‐wave complex with left central prevalence was induced. Various types of stimulation were used to induce epileptic discharges, and a simultaneous mental task requiring a high degree of concentration and complicated and delicate finger movements was necessary to induce the epileptic discharges. Comparison of our cases with previously reported reflex epilepsy induced by higher mental activity led to the assumption that the neural mechanism inducing seizures in our cases is similar to that of writing epilepsy. Valproate was effective in reducing epileptic discharges, and all patients became seizure‐free.

Les auteurs rapportent 3 cas d'épilepsie réflexe avec secousses myocloniques du bras droit et des doigts, provoqués par le calcul au moyen d'un soroban. Sur l'EEG, des pointes‐ondes prédominant sur la région centrale gauche ont également été induites. Différents types de stimulations ont été réalisés, et les auteurs ont constaté qu'il était indispensable qu'il y ait de façon simultanée un travail mental impliquant un degréélevé de concentration et des mouvements compliqués et délicats au niveau des doigts, pour obtenir l'induction des décharges épileptiques. La comparaison entre ces cas et ceux ayant rapporté une épilepsie réflexe induite par une activité mentale a conduit les auteurs àévoquer un mécanisme semblable à celui qui provoque les crises dans l'épilepsie de l'écriture. Le valproate s'est montré efficace dans la réduction des décharges et tous les patients ont été totalement contrôlés par ce médicament.

Wir berichten über 3 Fälle von Reflexepilepsie mit myoklonischen Zuckungen von rechtem Arm und Fingern, die durch Benutzung des Soroban augelöst wurden und im EEG mit linkszen‐traler Betonung von spike‐wave‐Komplexen einhergingen. Verschiedene Stimulations‐Modi wurden angewandt um epileptische Entladungen auszulösen: nur hohe Konzentration und komplizierte, feine Fingerbewegungen konnten epileptische Entladungen auslösen. Wenn wir unsere Fälle mit den bisher beschriebenen Reflexepilepsien vergleichen, die jeweils durch höhere mentale Aktivität ausgelöst wurden, kommen wir zu der Annahme, daβ die Anfälle induzierenden neuralen Mechanismen von unseren Fällen den der Schreibepilepsie ähnlich sind. Die epileptischen Entladungen sprachen gut auf Valproat an, die Patienten wurden anfallsfrei.
Photosensitive Epilepsies and Photoconvulsive Responses in Arabs
Authors: Obeid T. , Daif A. K. , Waheed G. , Yaqub B. , Panayiotopoulos C. P. , Tahan A. R. , Shamena A.
Published: November 2007

SUMMARY: The occurrence of photosensitivity (PS) was examined in 327 Arabs ≥15 years of age with epilepsy by intermittent photic stimulation (IPS). A control group of 192 nonepileptic Arabs ≥15 years of age were also examined by IPS. Of the epileptic patients, 24 (7.3%) were photosensitive, an incidence comparable to that in whites in contradistinction to the reported rarity among African blacks. This finding indicates that environmental factors, particularly excessive sunshine, does not appear to influence the occurrence of PS among epileptic patients. The occurrence of PS among epileptic patients may depend more strongly on the presence of an epileptic syndrome known to have association with PS.

La survenue d'une photosensibilité a étéétudiée chez 327 patients arabes présentant une épilepsie, âgés de 15 ans et plus. Un groupe contrôle de 192 arabes non épileptiques âgés de 15 ans et plus a également été examiné au moyen d'une stimulation lumineuse intermittente. Parmi les patients épileptiques, 24 (7.3%) présentaient une photosensibilité. Cette incidence est comparable à celle constatée dans les populations caucasiennes, en contraste avec la rareté de ce trait parmi les noirs africains. Ces constatations indiquent que les facteurs d'environnement, particulièrement l'ensoleillement excessif, ne semblent pas influencer la survenue d'une photosensibilité parmi les patients épileptiques. La survenue d'une photosensibilité chez les patients épileptiques pourrait dépendre davantage de la présence d'un syndrome épileptique fortement associéà la photosensibilité.

La aparición de fotosensibilidad (PS) ha sido examinada en 327 árabes con epilepsía de 15 años de edad y mayores. También se examinó un grupo control de 192 árabes de 15 años y mayores pero no epilépticos. Del grupo de epilépticos, 24 (7.3%), fueron fotosensibles lo que constituye una incidencia comparable a la publicada entre los individuos caucasianos y está en contradictión con lo que se ha publicado como una rareza entre los negros africanos. Este hallazgo indica factores ambientales, particularmente el excesivo sol, no parecen influenciar la aparición de PS entre los enfermos epilépticos. La presencia de PS en enfermos epilépticos puede depender más de la presencia de un síndrome epiléptico que, en si, muestra una fuerte asociación con la PS.

Das Auftreten von Photosensibilität (PS) wurde bei 327 Ara‐bern mit Epilepsie nach dem 15. Lebensjahr untersucht. Als Kontrollgruppe dienten 192 nicht‐epileptische Personen ab 15 Jahren. Von den Epilepsiekranken waren 24 (7.3%) photosensibel. Dies entspricht der Häufigkeit bei Kaukasiern, nicht aber der schwarzer Afrikaner, die seltener PS aufweisen. Diese Ergebnisse zeigen, daß Umweltfaktoren wie starke Sonneneinstrahlung das Auftreten von PS nicht beeinflussen. Das Merkmal PS bei epileptischen Patienten könnte eher von der Existenz eines epileptischen Syndroms abhängig sein, welches eng mit der PS verbunden ist.
Neurochemical and Behavioral Aspects of Lamotrigine
Authors: Leach M. J. , Baxter M. G. , Critchley M. A. E.
Published: November 2007

Summary: Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol‐induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine‐evoked release of glutamate when a threshold depolarizing concentration (4 μg/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 μg/ml). However, LTG does not block potassium‐evoked transmitter release. LTG is a less potent inhibitor of the release of γ‐aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP‐like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
Reproductive Function in Epilepsy
Authors: Cramer Joyce A. , Jones Ervin E.
Published: November 2007

Summary: : The hypothalamic‐pituitary‐gonadal axis is a complex system within which both positive and negative feedback occur among its elements and higher brain systems. The occurrence of seizures and changes in the secretion of pituitary hormones can affect the feedback loop. Both seizures and antiepileptic drugs can affect the hypothalamic‐pituitary‐gonadal axis of males and females and cause changes in hormones and sexuality. Reproductive dysfunction has a social impact because of reduced fertility. Once conception occurs, live birth rates are not diminished. Prospective studies of men and women with epilepsy are needed.
Reproductive Endocrine Considerations and Hormonal Therapy for Men with Epilepsy
Authors: Herzog Andrew G.
Published: November 2007

Summary: Androgen deficiency is unusually common among men with epilepsy. It may contribute to reproductive and sexual dysfunction and possibly exacerbate seizure frequency. The most important androgen is testosterone. It exists in the serum in a free form or bound to albumin or sex hormone‐binding globulin (SHBG). Free testosterone levels have correlated significantly with measures of potency and sexual interest. The possibility that measures of non‐SHBG‐bound testosterone may provide a more sensitive assessment of biologically and perhaps clinically significant androgen levels is raised for consideration. Androgen deficiency may result from increased catabolism and binding induced by antiepileptic drugs (AEDs). It is a feature of the reproductive endocrine disorders that are often associated with epilepsy: hypogonad‐otropic hypogonadism, hypergonadotropic hypogonadism, and functional hyperprolactinemia. It may be a consequence of medication‐induced elevations in serum estradiol. Estradiol exerts a potent inhibitory influence on luteinizing hormone secretion and may contribute to premature aging of the reproductive system, both at the level of the testes and the hypothalamus. Testosterone therapy may moderately benefit reproductive and sexual function. Despite its antiseizure effects in animal experiments, however, it has not been reported to improve seizures clinically. One possible explanation is that AEDs that induce enzyme synthesis may enhance the conversion of testosterone to estradiol by aromatase. This possibility is supported by the improved seizure control achieved with the adjunctive use of the aromatase inhibitor testolactone or the antiestrogen clomiphene.
Effects of Antiepileptic Drugs on Hormones
Authors: Ramsay R. Eugene , Slater Jeremy D.
Published: November 2007

Summary: : A hormone is an intrinsic substance carried via the blood to a target organ which is then functionally stimulated. Similar to extrinsically administered medications, the metabolism and function of the hormones may be altered by antiepileptic drugs (AEDs). The proposed mechanisms are (a) enhanced metabolism (natural steroids, synthetic steroids, e.g., decadron and birth control pills, thyroxine, and vitamin D3), (b) altered protein bonding (thyroxine, sex hormones), (c) impaired release into the systemic circulation (calcitonin, insulin, vitamin K clotting factors) and (d) altered end‐organ effect. The AEDs most likely to interact with hormones are barbiturates, carbamazepine, and phenytoin.