Showing papers on "Epileptogenesis published in 1990"

Post‐Traumatic Epilepsy: Cellular Mechanisms and Implications for Treatment

Abstract: Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate peroxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving gamma-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment. Language: en

Carbamazepine blocks NMDA-activated currents in cultured spinal cord neurons.

Abstract: The antiepileptic agents, carbamazepine and phenytoin, suppress seizures in man and convulsant-induced hyperactivity in spinal cord nerve cell cultures. In the present study, we have shown by whole cell recording that carbamazepine, in contrast to phenytoin, blocks N-methyl-D-aspartate (NMDA)-activated membrane currents in cultured neurons in a dose-dependent fashion. The NMDA receptor-activated channel, which is blocked at physiological concentrations of Mg2+ at resting membrane potential, can be activated by glutamate in depolarized neurons and thus be involved in epileptogenesis. Therefore, the block of NMDA-evoked membrane currents in cultured neurons may contribute to the clinical effectiveness of carbamazepine.

Chaos, balance, and development: thoughts on selected childhood epilepsy syndromes.

Abstract: 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.

Erosion of Kindled Epileptogenesis and Kindling-Induced Long-Term Seizure Suppressive Effect in Primates

Abstract: Repeated electrical stimulation of the brain can result in the development of spontaneous recurrent seizures in dogs, cats and rats (10, 49, 51) or status epilepticus in dogs and cats (1, 49). In primates, Delgado (7) found that repeated electrical brain stimulation results in a lasting change in the EEG signature of induced seizure. Subsequently, the critical conditions necessary for progressive changes induced by repeated electrical brain stimulation were identified by Goddard who baptized it “the kindling phenomenon” (15, 16). His original studies were primarily in rodents, but he was the first to extend the observation to primates, with the specific intention of verifying the validity of the kindling phenomenon across the species. Although considerable difficulty was encountered in identifying the optimal parameters of stimulation, and despite considerable variation in the results obtained, he was able to conclude that unilateral or bilateral clonic seizure can be induced after six months of stimulation„ Furthermore, once established, a rest interval of eight weeks did not weaken the kindled response in the rhesus monkey. In the meantime, spontaneous seizure development was being documented in nonepileptic patients who underwent either a series of ECTs (33), or prolonged intracerebral electrical stimulation (24, 35). All these findings strongly suggest that, in response to repeated electrical brain stimulation, the progressive development and acquisition of lasting seizure suceptibility which culminate in the emission of spontaneous seizures are the likely biological principles operating in all mammalian species, including man.

The epileptic focus versus the pathological focus.

Abstract: The relationship between the epileptic focus and the causative lesion has been studied to define when resection of the epileptic focus may be associated with removal of the lesion. Experimental studies reveal that a maturation phase is followed by a progressive autonomisation of the epileptic focus from the induced lesion. Thereafter there may be a progressive course to such experimental epilepsy with spreading of the epileptic lesions and possible creation of a secondary focus. However, in man the findings are less coherent and sometimes contradictory. In long term intractable epilepsy, simple removal of the causative lesion can be effective. A hypothesis is proposed to explain these phenomena — the hypothesis of systemic focal epileptogenesis. It is further proposed that endogenous excitotoxic agents such an quinolinic acid may have effects on the epileptic focus only when the causative lesion is present producing a subtle modification of the blood brain barrier.

Contribution of calcium ions to epileptogenesis.

Abstract: With epileptic activity neurons show typical paroxysmal depolarization shifts (PDS) (Speckmann, 1986). Experimental findings indicate that calcium and calcium-dependent currents participate in the generation of these events (Heinemann et al., 1986; Speckmann et al., 1986). Consequently, neuronal PDS were depressed by organic calcium channel blockers and so were seizure discharges in neuronal populations.

The Kindling Process and Vulnerability to Status Epilepticus

Abstract: Several years ago, we developed an experimental model of status epilepticus (SE) that exploited the interaction of pilocarpine and seizure discharge upon a background of epileptogenesis resulting from amygdala kindling (1). We were initially interested in using the model to study the mechanisms by which the sustained seizures were initiated and maintained. However, we were struck by the extensive bilateral neuropathology resulting from a relatively short duration of SE in our model compared to other models of SE using pilocarpine (2, 11). We naturally wondered if the kindling process established an increased vulnerability to seizure-induced damage. If so, we reasoned that elucidation of the mechanisms responsible for the enhanced vulnerability might reveal information about the mechanisms underlying the acquisition of kindled seizures. Described here is some of the work that evolved from this idea, the results of which indicate that kindling does indeed alter vulnerability to SE, but also that the picture is more complex than we had originally envisioned.