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Management of Absence Seizures. Treatment Goals. Block repetitive neuronal firing Block synchronization of neuronal discharges Block propagation of seizure Minimize side effects with the simplest drug regimen. Treatment Strategies. Modification of ion conductances
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Treatment Goals • Block repetitive neuronal firing • Block synchronization of neuronal discharges • Block propagation of seizure Minimize side effects with the simplest drug regimen.
Treatment Strategies • Modification of ion conductances • Increase inhibitory (GABA) transmission • Decrease excitatory (glutamate) activity
The dynamic target of seizure control in the management of epilepsy is achieving balance between the factors that influence the excitatory postsynaptic potential (EPSP) and those that influence inhibitory postsynaptic potential (IPSP)
Absence Seizures • Often begin during childhood (daydreaming attitude, no participation, lack of concentration) • A low threshold Ca2+ current has been found to govern oscillatory responses in thalamic neurons and it is probably involved in the generation of this type of seizures
ethosuximide • DOC for Absence seizures • Mechanism of action involves reducing low-threshold Ca2+ channel current (T-type channel) in thalamus At high concentrations: • Inhibits Na+/K+ ATPase • Depresses cerebral metabolic rate • Inhibits GABA aminotransferase • Phensuximide = less effective • Methsuximide = more toxic
Low-voltage calcium (Ca2+) currents (T-type) are responsible for the rhythmic thalamocortical spike and wave patterns of generalized absence seizures. Some antiepileptic drugs lock these channels, inhibiting the underlying slow depolarizations necessary to generate spike-wave bursts.
ethosuximide • Toxicity drowsiness, dizziness, weight gain, agitation, confusion ,psychosis • Alternative drug for ethosuximide: • valproic acid
Non-pharmacologic Management • Head cooling • Diet • neurostimulation