Anticonvulsants* ; Pharmacogenetics*

Epilepsy* ; Genetics*

No abstract available.
Neuropeptides* ; Seizures*

No abstract available.

No abstract available.
Epilepsy, Temporal Lobe* ; Hippocampus* ; Parturition* ; Temporal Lobe*

No abstract available.
Anticonvulsants*

No abstract available.
Anticonvulsants* ; Drug Interactions*

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed prior to 1980 appear to act on sodium channels, gamma-amino butyric acid type A (GABA(A)) receptors or calcium channels. Benzodiazepines and barbiturates enhance GABA(A) receptormediated inhibition. Barbiturates increase the duration of chloride channel opening and at higher doses, they block voltage-dependent calcium channels presynaptically, decreasing excitatory amino acid (EAAs) transmission. Benzodiazepines also interact with the GABA(A) receptor complex and increase the frequency of chloride channel opening. Phenytoin, carbamazepine and possibly sodium valproate decrease high frequency repetitive firing of action potentials by enhancing sodium channel inactivation. At higher doses, PHT may block sodium channels presynaptically and decrease EAAs release. In addition to the action on sodium channel, CBZ interacts with adenosine receptor and decrease C-AMP, and block reuptake of norepinephrine. VPA shows diverse mechanisms including sodium channel blocking. It increases synaptosomal GABA by increasing production and decreasing break-down and interacts with T-type calcium channels preventing thalamocortical interaction necessary for absence. Ethosuximide and sodium valproate reduce a low threshold (T-type) calcium channel current. The mechanisms of action of newly developed AEDs are not fully established. Felbamate is broad-spectrum, and probably has multiple actions on sodium channels, interaction with GABA(A) receptors, and interaction with NM.D.A receptors. Gabapentin binds to a high affinity site on neuronal membranes in a restricted regional distribution of the CNS. This binding site may be related to a possible active transport process of gabapentin into neurons. However this has not proven and the mechanism of action of gabapentin remains uncertain. It is structurally related to GABA and its action of antiepileptic activity is suspected due to change of neuronal amino acids (interfere glutamate synthesis, block GABA uptake, and enhance GABA release). Lamotrigine, initially developed as an antifolate drug, decreases sustained high frequency repetitive firing of voltage-dependent sodium action potentials that may result in a preferential decreased release of presynaptic glutamate. It may also interact with GABA receptors but its primary antiepileptic action is on the sodium channel similar to the PHT and CBZ. Because of such a diverse mechanism of action, LTG is one of the wide spectrum AEDs. Oxcarbazepine's mechanism of action is not known ; however, its similarity in structure and clinical efficacy to that of carbamazepine suggests that its mechanism of action may involve inhibition of sustained high frequency repetitive firing of voltage-dependent sodium action potentials. Vigabatrin is a "designer" drug as is developed rationally, and it reversibly inhibits GABA transaminase, the enzyme that degrades GABA, thereby producing greater available pools of presynaptic GABA for release in central synapses. Increased activity of GABA at postsynaptic receptors may underlie the clinical efficacy of VGB. Tiagabine is a potent blocker of GABA re-uptake by glia and neuron.
4-Aminobutyrate Transaminase ; Action Potentials ; Amino Acids ; Anticonvulsants* ; Barbiturates ; Benzodiazepines ; Binding Sites ; Biological Transport, Active ; Butyric Acid ; Calcium Channels ; Calcium Channels, T-Type ; Carbamazepine ; Chloride Channels ; Ethosuximide ; Excitatory Amino Acids ; Fires ; gamma-Aminobutyric Acid ; Glutamic Acid ; Ion Channels ; Membranes ; Neuroglia ; Neurons ; Neurotransmitter Agents ; Norepinephrine ; Phenytoin ; Receptors, GABA ; Receptors, GABA-A ; Receptors, Neurotransmitter ; Receptors, Purinergic P1 ; Sodium ; Sodium Channels ; Synapses ; Valproic Acid ; Vigabatrin

OBJECT: Surgical treatment of cortical dysplasias (CDs) presenting with intractable seizures is challenging, because isualization/localization of the lesion is difficult, correlation with seizure foci needs comprehensive investigations, and the reported surgical results are not satisfactory. We report our result of surgical treatment of CD classified from the surgical point of view. METHODS: Definition of CD was a visible dysplastic lesion on MRI or MRI-negative (normal MRI) case with pathological diagnosis of moderate to severe dysplasia. During the last 4.5 years, we had operated on 36 cases of intractable epilepsy with CDs. We divided the 36 cases into 4 groups ; Group A : diffuse bilateral hemispheric dysplasia, Group B : diffuse lobar dysplasia, Group C : focal dysplasia, and Group D : moderate to severe degree of cortical dysplasia with normal MRI. All but one patient in Group C were monitored at EMU using subdural electrodes for seizure localization and functional mapping. RESULTS: The incidence of CD in the whole epilepsy surgery cases was 12.4%. Mean age was 21.3 years. Mean age at seizure onset was 8.5 years. Mean follow up period was 26.0 months. Twenty-six (72.2%) patients (20 and 6, respectively) belong to Engel Class I and II. There were 5, 9, 9, and 13 cases in Groups A, B, C, and D, respectively. Groups A and B had significantly lower age at seizure onset and significantly poorer surgical outcome compared to Groups C and D (p<0.05). If the outcome was compared on the extent of removal of CD, patients with completely removed CD had very significantly better outcome than those with partial removal (p<0.001). CONCLUSIONS: We conclude that intractable epilepsy with CD can be treated surgically with comprehensive preoperative approaches. Deliberate resective procedures aiming at complete removal of dysplastic tissue ensure excellent seizure control without permanent neurological deficit.
Diagnosis ; Dromaiidae ; Electrodes ; Epilepsy ; Follow-Up Studies ; Humans ; Incidence ; Magnetic Resonance Imaging ; Malformations of Cortical Development* ; Seizures*

No abstract available.
Malformations of Cortical Development*