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Generalized epilepsy with bilateral synchronous spike and wave discharge. New findings concerning its physiological mechanisms.

A hypothesis for the mechanism of generalized spike and wave discharge in human generalized epilepsy is proposed in the light of findings obtained in feline generalized penicillin epilepsy. It is postulated that generalized bilaterally synchronous spike and wave discharge depends upon a diffuse and relatively mild state of cortical hyperexcitability which increases the responsiveness of cortical neurons. Afferent thalamo-cortical volleys normally involved in the genesis of spindles and recruiting responses are most likely to precipitate spike and wave discharges under these conditions. The spike and wave pattern probably results from the activation of a recurrent intracortical inhibitory pathway which becomes activated when cortical neurons discharge in greater number and more repetitively than is normally the case. During spike and wave discharges a large number of neurons oscillate between short periods of excitation, corresponding to the spike, and longer periods of inhibition, corresponding to the slow wave component of the spike and wave complex. This disrupts the normal transactional processes of cortical neurons which are presumably responsible for mental activity, particularly for the close integration of perception, cognition and voluntary motor responsiveness. The degree of this interference varies greatly and in mild absence seizure it is not justified to speak of "loss of consciousness". The fundamental disturbance in absence seizures brought about by the generalized cortical spike and wave discharges is therefore better regarded as a "clouding of the mind". Loss of consciousness can be said to occur only when the interference with mental activity becomes particularly intense. Loss of consciousness in absence seizures can therefore not be used as an argument in favor of primary involvement of higher brain-stem mechanisms.

Animals

[The treatment of primary generalized epilepsies with dipropyl acetate (DPA)].

79 patients with primary generalized epilepsies have been treated with DPA in a medium dosage of 51 mg/kg bodyweight/day, range 14 to 125 mg/kg/day, for a medium time of 22 months, range 2 to 49 months. 51 children out of this group had been treated previously and were therapy resistant to other medications. 27 children got DPA for their first medication. 34 patients were treated with DPA as a single drug, 45 were treated in combination with other medications. Therapeutic success was found to be remarkable good in impulsive petit mal (n = 4, all patients without any more seizures), in absences (n = 52, complete success in 84%), and in primary generalized grand mal seizures with spike-waves in the EEG alone or in combination with petit mal (n = 30, 87% success). However, centrencephalic myoclonic-astatic seizures (n = 17, no more seizures in 35%) were influenced significantly less. Side effects were rarely seen, mostly they could be observed in those patients treated with DPA and another medication. Side effects never induced interruption of treatment with DPA.

Adolescent

Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ("epilim").

A total of 142 patients (84 per cent aged less than 20 years) with various forms of generalized epilepsy have been treated with sodium valproate alone or in combination with other drugs. The mean duration of symptoms was six years, and half the patients had daily seizures. Nine patients had typical absences, 33 had absences with automatisms, 28 had tonic-clonic seizures with or without photosensitivity, and 72 had various forms of myoclonic epilepsy. Dosage varied from 23 to 54mg/kg and twice-daily administration was usual. Estimation of serum levels did not assist in management. Fits ceased in 63 per cent of all cases and a further 18 per cent showed improvement greater than 50 per cent. Of the 69 with 3c/sec spike-and-wave discharges, 81 per cent became free from all fits, as did 77 percent of those with myoclonic jerks. Fits ceased in eight of the 32 patients with myoclonic astatic epilepsy and there was improvement greater than 50 per cent in a further eight patients. Other anticonvulsants were often withdrawn and always reduced. 21 patients received sodium valproate alone from the start of treatment and all other drugs were withdrawn in another 38. Sodium valproate alone controlled all fits in four children with absences, in 18 with absences with automatisms, 10 with tonic-clonic seizures and 22 with myoclonic epilepsy. Side-effects were rare, mild and often temporary. Potentiation of barbiturates and benzodiazepines occurred, especially clonazepam, which should be avoided. Many patients were more alert. Sodium valproate appears to be the drug of choice for epilepsies associated with generalized spike-and-wave discharges, myoclonic epilepsies or photosensitive epilepsies, and is of especial value in children and mentally retarded patients because it lacks sedating effects and often induces liveliness.

Adolescent

[Generalized epilepsies].

Short revaluation of present status of the concept of primary and secondary generalized epilepsy and of neurophysiopathological differences supporting such distinction.

Adult

Selective amplitude histograms: a statistical approach to EEG-single unit relationships in generalized epilepsy.

Statistical analysis techniques that permit detection and quantification of EEG-single unit correlations were employed in a study of generalized penicillin epilepsy in the cat. Single unit activity was recorded in cerebral and cerebellar cortices and compared to the locally recorded EEG. It was found that during generalized paroxysmal activity the background EEG was significantly related to the time of occurrence of unit discharge. The degree of synchrony of various units differed but tended to increase as the duration and extent of paroxysmal activity increased. These relationships were usually not evident upon visual inspection of the original unprocessed data but were consistently detected by the analysis techniques described here. The results demonstrate the usefulness of a statistical approach to the analysis of single unit data and suggest that, not only is there a significant relationship between paroxysmal events and neuronal activity in generalized penicillin epilepsy, but also an overall trend to closer synchronization of EEG and single unit discharges during nonparoxysmal periods.

Action Potentials

Carbamazepine vs phenytoin. A controlled clinical trial in focal motor and generalized epilepsy.

The antiepileptic effects of carbamazepine and phenytoin were compared in a double-blind crossover trial studying patients with primary and secondary generalized seizures and partial seizures with motor symptoms. Each treatment period lasted ten weeks. The patients were seen every two weeks, and doses were adjusted according to plasma levels. It was attempted to keep levels in the optimal plasma range, ie, 10 to 20 and 4 to 10 mg/liter for phenytoin and carbamazepine, respectively. Twenty-three patients entered and 19 completed the study. No statistically significant differences were found between carbamazepine and phenytoin with regard to seizure control and acute side effects.

Adolescent

[Frontal, or generalized, epilepsy].

The author studied the results of surgical treatment of 28 epileptic patients where the localization of the epileptogenic focus was on the medial surface of the hemisphere in the area of the frontal pole or on the lateral surface. Taking into consideration the theoretical premises, an analysis of literary data and the results of a comprehensive clinical study of patients the author comes to the conclusion that for a localization of the epileptogenic focus in the area of the pole and medio-basal parts of the frontal lobes primary generalized epileptic seizures and distant synchronous bioelectrical activity in the EEG without distinct focal changes are most characteristic.

Epilepsy

Neuropathology of secondary generalized epilepsy--(Lennox-Gastaut syndrome)--a case report.

Neuropathological considerations were performed on a case, who went into Lennox syndrome after an acute encephalopathy at the infantile period, and moreover who fell into an akinetic-mute state derived from brain damage by herniation caused by a head injury and subsequent status epilepticus. Neuropahtological background in the present case of Lennox syndrome is thought to be based on the widespread unilateral cerebral lesions and the basal ganglional, especially thalamic, degenerations derived secondarily from the diffuse cerebral damage. The patient revealed akinetic mutism with the disappearance of the epileptic seizures and the desynchronization of the EEG's, when the brain lesions formed at the adult period spread over the opposite hemispheric limbic system and the brain stem tectum.

Adult

Appearance of EEG changes reminiscent of a secondary generalized epilepsy in a rhesus monkey inoculated with a strain of kuru.

In a group of rhesus monkeys (Macaca mulatta) inoculated intracerebrally and intravenously with a strain (Enage strain rhesus L6 56) of kuru already passaged in rhesus monkeys, 1 monkey presented the typical EEG pattern of epileptogenic encephalopathy reminiscent of the Lennox-Gastaut syndrome. This observation provides no direct evidence for the viral origin of epilepsies of this type. It does, however, show that it is possible to induce an epileptogenic encephalopathy by an unconventional infectious agent.

Animals