[Treatment of petit mal-absence].
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In order to assess the possible association of cytomegalovirus (CMV) with cerebral damage, 65 children aged between 2 and 10 years were tested for CMV isolation and antibody status. All of them had previously presented one or more episodes of febrile convulsions. At the time of our study, they were grouped according to their clinical features and electroencephalogram (EEG). 21 had typical and/or atypical absence attacks with 3 c/s spike-wave EEG (primary generalized epilepsy), 21 presented febrile seizures and spontaneous fits with focal EEG abnormalities, 23 had no seizures and a normal EEG. We performed the same investigation in 41 healthy children. The study showed a similar isolation rate of CMV in healthy subjects and in patients without neurological and EEG alterations, while a significantly higher isolation rate was observed in the groups with neurological and EEG abnormalities. As for serology, no significant difference was observed between the four groups, although the positivity rate of the healthy children was lower than in the other three groups. The study suggests a possible association of CMV with neurological and EEG abnormalities after febrile seizures.
All electroencephalograms performed in our institution between 1980 and 1990 were reviewed. The clinical characteristics of children with epilepsy and generalized spike-and-wave (SW) patterns were analyzed. The SW patterns were classified according to their frequency. Electroencephalograms of 154 children with epilepsy revealed SW patterns. Absence seizures were the most common first seizure, but partial seizures were frequent. More than 40% had several types of seizures. Sixty percent of the epileptic syndromes were generalized, but almost 25% were partial. The typical SW pattern was associated with absence seizures, a normal examination and computed tomographic scan, idiopathic generalized epilepsies, monotherapy, freedom from seizures, and lack of recurrence. The slow SW pattern was associated with West syndrome; a younger age at seizure onset; atonic, myoclonic, tonic, and partial simple seizures; an abnormal examination and computed tomographic scan; cryptogenic or symptomatic generalized epilepsy or symptomatic partial epilepsy; polytherapy; and poor seizure control. The fast SW pattern was associated with secondary generalized, partial, tonic-clonic, and complex partial seizures; a normal computed tomographic scan; cryptogenic partial epilepsy; isolated seizures; and seizure recurrence. Epilepsy with a typical SW pattern should be considered benign, epilepsy with a slow SW pattern malignant, and epilepsy with a fast SW pattern treacherous.
There are several new antiepileptic drugs undergoing extensive clinical investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and oxcarbazepine--appear to be the most widely tested and promising agents. Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is also effective in infantile spasms, but seems to have negative effects on myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition, lamotrigine and felbamate seem to have efficacy in idiopathic generalised epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine, but less toxic. Gabapentin has few adverse effects and has efficacy in some patients with drug-resistant partial epilepsy. Some of the new antiepileptic drugs modify excitatory or inhibitory amino acid transmission, but some of them may employ new, still unknown mechanisms of action. Depending on the mechanism of action, the therapeutic effectiveness of the antiepileptic drugs may differ in specific epileptic syndromes. Future antiepileptic drugs may thus give us the possibility to design rational polypharmacy for individual patients by combining agents with different spectra of effectiveness. Considering the goal of good tolerability in the development of the new antiepileptic drugs, polypharmacy with these agents is not expected to increase adverse effects significantly.
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Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) is a novel neurosteroid which has anticonvulsant properties in a number of seizure models as well as the ability to enhance function of the gamma-aminobutyric acid-A (GABA(A)) receptor complex via a neurosteroid binding site. The object of these experiments was to ascertain the efficacy of ganaxolone against absence seizures. Ganaxolone was assessed in the low-dose pentylenetetrazol (PTZ) and the gamma-hydroxybutyric acid (GHB) model of absence seizures in rats. Ganaxolone pretreatment resulted in a significant prolongation of absence seizure in both the PTZ and GHB models. Further, ganaxolone in doses above 20 mg/kg alone produced bilaterally synchronous spike wave discharges (SWDs) associated with behavioral arrest. These data suggest that augmentation of GABA(A) receptor complex function by neurosteroids has the potential to result in or exacerbate absence seizures.
PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.
Two hundred and seventy eight absence seizures were recorded from 60 patients by an intensive monitoring device. They were divided into two subtypes, typical and atypical absences based on their ictal discharges whether the spike-wave rhythm was at 3 cps or not. These two absence seizures did not differ so much with regard to loss of consciousness except that: 1) the durations of discharge in atypical absences were longer than those of typical ones, 2) the recovery from clouded consciousness to a state of full-awareness was apparently delayed in atypical absences after the termination of epileptic discharges, 3) the oral automatisms were more associated with typical absences and the decreased postural tones with atypical absences. By a numerical analysis of two parameters of spike-wave, that is, its frequency ad rhythmicity, it was shown that absences with spike-waves slower than 30 cps and with poor rhythmicity which roughly corresponded with atypical absences were more therapy-resistant in comparison with those having 3 cps spike waves and good rhythm which were usually typical absences. Sodium valproate was more effective on typical absences, however, there was no difference between typical and atypical absences in the therapeutic maintenance concentrations of serum valproate acid. We would like to emphasize that the comparison of the symptomatology between typical and atypical absences is of significance not only for understanding the etiology of the epilepsies but for the guideline of practical pharmacotherapy.
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Nowadays epilepsy is classified according to the international classification of epilepsies, epileptic syndromes and related disorders proposed by International League Against Epilepsy (ILAE, 1989). Among these epilepsies and epileptic syndromes, I detailed the clinical symptomatology and the clinical significance of benign familial neonatal convulsions, juvenile myoclonic epilepsy, epilepsy with myoclonic absence, mesial temporal lobe epilepsy and chronic progressive epilepsia partialis continua of childhood. Of 218 patients with temporal lobe resection who were followed for over 2 years, 172 patients or 79% were seizure free according to Engel's criteria of seizure outcome after surgical treatment. Of 66 patients with extra-temporal lobe epilepsy, 43 patients or 65% were seizure free. From the postsurgical outcome I talked about the need of strict presurgical evaluation to have the good postsurgical outcome. The neuropathology of surgically resected 278 specimens of temporal lobe epilepsy was mesial temporal sclerosis in 184, neuroepithelial tumors in 66, cortical malformation in 11, vascular anomaly in 13, and others in 4. Thirty-nine of resected 66 specimens of extra-temporal lobe epilepsies were cortical malformation. I presented the recent progress of genetic study in epilepsies and stressed the importance of correct diagnosis of epilepsy for genetic study.
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This chapter has reviewed the multiple types of childhood epilepsies customarily referred to as "myoclonic epilepsies" and has made an attempt at classification. A distinction was made on a clinical neurophysiological basis between true myoclonic and pseudomyoclonic seizures that include brief tonic and atonic attacks. The epilepsies characterized mainly by pseudomyoclonic seizures include infantile spasms (West's syndrome) and the Lennox-Gastaut syndrome. The epilepsies manifested principally by true myoclonic seizures comprise two subgroups: a symptomatic type, in which myoclonias are the result of fixed diffuse brain damage; and several cryptogenic forms. The latter may be divided, according to age of onset and clinical features, into several myoclonic syndromes: cryptogenic myoclonic epilepsy of infancy and early childhood, myoclonic epilepsy of childhood with absences, and myoclonic epilepsy of adolescence. Many intermediate and atypical forms exist; thus the proposed classification is only tentative.
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