Epilepsy and Seizures

Published on February 2017 | Categories: Documents | Downloads: 49 | Comments: 0 | Views: 242
of 8
Download PDF   Embed   Report

Comments

Content

7/9/12

Epilepsy and Seizures

Medscape Reference Reference

News Reference Education MEDLINE

Epilepsy and Seizures
Author: Jose E Cavazos, MD, PhD, FAAN; Chief Editor: Selim R Benbadis, MD more... Updated: Dec 2, 2011

Pathophysiology
Seizures are paroxysmal manifestations of the electrical properties of the cerebral cortex. A seizure results when a sudden imbalance occurs between the excitatory and inhibitory forces within the network of cortical neurons in favor of a sudden-onset net excitation. If the affected cortical network is in the visual cortex, the clinical manifestations are visual phenomena. Other affected areas of primary cortex give rise to sensory, gustatory, or motor manifestations. The pathophysiology of focal-onset seizures differs from the mechanisms underlying generalized-onset seizures. Overall, cellular excitability is increased, but the mechanisms of synchronization appear to substantially differ and are therefore discussed separately. For a review, see the epilepsy book of Rho, Sankar, and Cavazos.[3]

Pathophysiology of Focal Seizures
The clinical neurophysiologic hallmark of focal-onset seizures is the focal interictal epileptiform spike or sharp wave. The cellular neurophysiologic correlate of an interictal focal epileptiform discharge in single cortical neurons is the paroxysmal depolarization shift (PDS). The PDS is characterized by a prolonged calcium-dependent depolarization that results in multiple sodium-mediated action potentials during the depolarization phase, and it is followed by a prominent after hyperpolarization, which is a hyperpolarized membrane potential beyond the baseline resting potential. Calcium-dependent potassium channels mostly mediate the after-hyperpolarization phase. When multiple neurons fire PDSs in a synchronous manner, the extracellular field recording shows an interictal spike. If the number of discharging neurons is more than several million, they can usually be recorded with scalp electrographic (EEG) electrodes. Calculations show that the interictal spikes need to spread to about 6 cm2 of cerebral cortex before they can be detected with scalp electrodes. Several factors may be associated with the transition from an interictal spike to an epileptic seizure. When any of the mechanisms that underlie an acute seizure become a permanent alteration, patients are assumed to then develop a propensity for recurrent seizures (ie, epilepsy). The mechanisms discussed below may coexist in different combinations to cause focal-onset seizures. If the mechanisms leading to a net increased excitability become permanent alterations, patients develop pharmacologically intractable focal-onset epilepsy. Current available medications were screened using acute models of focal-onset or generalized-onset convulsions. In clinical use, they are most effective at blocking the propagation of a seizure (ie, spread from the epileptic focus to secondary generalized tonic-clonic seizures). Further understanding of the mechanisms that permanently increase network excitability may lead to development of true antiepileptic drugs that alter the natural history of epilepsy.
emedicine.medscape.com/article/1184846-overview#a0104 1/8

7/9/12

Epilepsy and Seizures

Mechanisms leading to decreased inhibition and those leading to increased excitation are discussed in this section. Mechanisms leading to decreased inhibition include the following: Defective gamma-aminobutyric acid (GABA)–A inhibition Defective GABA-B inhibition Defective activation of GABA neurons Defective intracellular buffering of calcium

Defective GABA-A inhibition
GABA is the main inhibiting neurotransmitter in the brain, and it binds primarily to 2 major classes of receptors: GABA-A and GABA-B. GABA-A receptors are coupled to chloride channels, and they are one of the main targets modulated by the anticonvulsant agents that are currently in clinical use. The reversal potential of chloride is about -70 mV. The contribution of chloride channels during resting potential in neurons is minimal, because the typical resting potential is near -70 mV, and thus there is no significant electromotive force for net chloride flux. However, chloride currents become more important at more depolarized membrane potentials. These channels make it difficult to achieve the threshold membrane potential necessary for an action potential. The influence of chloride currents to the neuronal membrane potential increases as the neuron becomes more depolarized by the summation of the excitatory postsynaptic potentials (EPSPs). In this manner, they become another force that must be overcome to fire an action potential, decreasing excitability. Properties of the chloride channels associated with the GABA-A receptor are often clinically modulated by using benzodiazepines (eg, diazepam, lorazepam, clonazepam), barbiturates (eg, phenobarbital, pentobarbital), or the anticonvulsant topiramate. Benzodiazepines increase the frequency of openings of chloride channels, whereas barbiturates increase the duration of openings of these channels. Topiramate increases the frequency of channel openings, but it binds to a site different from the benzodiazepine-receptor site. Either benzodiazepines or barbiturates, but not both, appear to modulate individual chloride channels. Whether combining topiramate with either class of agents increases the chloride currents is unknown. Alterations in the normal state of the chloride channels might increase membrane permeability and conductance of chloride ions. In the end, the behavior of all individual chloride channels sum up to form a large chloride-mediated hyperpolarizing current that counterbalances the depolarizing currents created by summation of excitatory postsynaptic responses (EPSPs) induced by activation of the excitatory input. The EPSPs are the main form of communication between neurons, and the release of the excitatory amino acid glutamate from the presynaptic element mediates EPSPs. Three main receptors mediate the effect of glutamate release in the postsynaptic neuron: N -methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4isoxazole propionic acid (AMPA)/kainate, and metabotropic, which are coupled by means of different mechanisms to several depolarizing channels. Inhibitory postsynaptic potentials (IPSPs), mediated mainly by the release of GABA in the synaptic cleft with postsynaptic activation of GABA-A receptors, temper these effects. All channels in the nervous system (and essentially any living organism) are subject to modulation by several mechanisms, such as phosphorylation and possibly a change in the tridimensional conformation of a protein in the channel. The chloride channel has several phosphorylation sites, one of which topiramate appears to modulate. Phosphorylation of this channel induces a change in normal electrophysiologic behavior, with an increased frequency of channel openings but for only certain chloride channels. Each channel has a multimeric structure with several subunits of different types. Chloride channels are no exception; they have a pentameric structure. The subunits are molecularly related but different proteins. The heterogeneity of electrophysiologic responses of different GABA-A receptors is due to different combinations of the subunits. In mammals, at least 6 alpha subunits and 3 beta and gamma subunits exist for the GABA-A receptor complex. A complete GABA-A receptor complex (which in this case is the chloride channel itself) is formed from 1 gamma, 2 alpha, and 2 beta subunits. The number of possible combinations of the known subunits is almost 1000; therefore, more than 1000 receptor types theoretically exist. In practice, only about 20 of these combinations have been found in the normal mammalian brain. Some epilepsies may be due to mutations or lack of expression of the different GABA-A receptor complex subunits, the molecules that govern their assembly, or the molecules that modulate their electrical properties. For example, hippocampal pyramidal neurons might not be able to assemble alpha 5 beta 3 gamma 3 receptors because of deletion of chromosome 15 (ie, Angelman syndrome).
emedicine.medscape.com/article/1184846-overview#a0104 2/8

7/9/12

Epilepsy and Seizures

Changes in the distribution of subunits of the GABA-A receptor complex have been demonstrated in several animal models of focal-onset epilepsy, such as the electrical-kindling, chemical-kindling, and pilocarpine models. In the last model, decreased concentrations of mRNA for the alpha 5 subunit of the surviving interneurons were observed in the CA1 region of the rat hippocampus.[4]

Defective GABA-B inhibition
The GABA-B receptor is coupled to potassium channels, forming a current that has a relatively long duration of action compared with the chloride current evoked by activation of the GABA-A receptor. Because of the long duration of action, alterations in the GABA-B receptor are thought to possibly play a major role in the transition between the interictal abnormality and an ictal event (ie, focal-onset seizure). The molecular structure of the GABA-B receptor complex consists of 2 subunits with 7 transmembrane domains each. G proteins, a second messenger system, mediate coupling to the potassium channel, explaining the latency and long duration of the response. In many cases, GABA-B receptors are located in the presynaptic element of an excitatory projection. Therefore, release of GABA from the interneuron terminal inhibits the postsynaptic neuron by means of 2 mechanisms: (1) direct induction of an IPSP, which a GABA-A chloride current typically mediates, and (2) indirect inhibition of the release of excitatory neurotransmitter in the presynaptic afferent projection, typically with a GABA-B potassium current. Once again, alterations or mutations in the different subunits or in the molecules that regulate their function might affect the seizure threshold or the propensity for recurrent seizures.

Defective activation of GABA neurons
GABA neurons are activated by means of feedforward and feedback projections from excitatory neurons. These 2 types of inhibition in a neuronal network are defined on the basis of the time of activation of the GABAergic neuron relative to that of the principal neuron output of the network, such as the hippocampal pyramidal CA1 cell. In feedforward inhibition, GABAergic cells receive a collateral projection from the main afferent projection that activates the CA1 neurons, namely, the Schaffer collateral axons from the CA3 pyramidal neurons. This feedforward projection activates the soma of GABAergic neurons before or simultaneously with activation of the apical dendrites of the CA1 pyramidal neurons. Activation of the GABAergic neurons results in an IPSP that inhibits the soma or axon hillock of the CA1 pyramidal neurons almost simultaneously with the passive propagation of the excitatory potential (ie, EPSP) from the apical dendrites to the axon hillock. The feedforward projection thus primes the inhibitory system in a manner that allows it to timely inhibit the pyramidal cell's depolarization and firing of an action potential. Feedback inhibition is another system that allows GABAergic cells to control repetitive firing in principal neurons, such as pyramidal cells, and to inhibit the surrounding pyramidal cells. Recurrent collaterals from the pyramidal neurons activate the GABAergic neurons after the pyramidal neurons fire an action potential. In the last few years, experimental evidence has indicated that some other kind of interneuron might be a gate between the principal neurons and the GABAergic neurons. In the dentate gyrus, the mossy cells of the hilar polymorphic region appear to gate inhibitory tone and activate GABAergic neurons. The mossy cells receive both feedback and feedforward activation, which they convey to the GABAergic neurons. However, in certain circumstances they appear highly vulnerable to seizure-related neuronal loss. After some of the mossy cells are lost, activation of GABAergic neurons is impaired.[5] Synaptic reorganization is a form of brain plasticity induced by neuronal loss, perhaps triggered by the loss of the synaptic connections of the dying neuron, a process called de-afferentation. Formation of new sprouted circuits includes excitatory and inhibitory cells, and both forms of sprouting have been demonstrated in many animal models of focal-onset epilepsy and in humans with intractable temporal-lobe epilepsy. Most of the initial attempts of hippocampal sprouting are likely to be attempts to restore inhibition, but as the epilepsy progresses, the overwhelming number of sprouted synaptic contacts occurs with excitatory targets, creating recurrent excitatory circuitries that permanently alter the balance between excitatory and inhibitory tone in the hippocampal network.

Defective intracellular buffering of calcium
Recurrent seizures induced by a variety of methods result in a pattern of interneuron loss in the hilar polymorphic region in rodents, with striking loss of the neurons that lack calcium-binding proteins parvalbumin and calbindin. In rat hippocampal sections, these interneurons demonstrate a progressive inability to maintain a hyperpolarized resting membrane potential; eventually, they die. An experiment in which researchers used microelectrodes containing the calcium chelator BAPTA demonstrated reversal of the deterioration in the membrane potential as the calcium chelator was allowed to diffuse in the interneuron[6] ; the experiment demonstrated the critical role of
emedicine.medscape.com/article/1184846-overview#a0104 3/8

7/9/12

Epilepsy and Seizures

adequate concentrations of calcium-binding proteins for neuronal survival in settings with sustained rises of intracellular calcium, such as in status epilepticus and other brain insults. This mechanism might be a possible contributor to medical intractability in some epilepsy patients. The vulnerability of interneurons to hypoxia and other insults also correlates to the relative presence of these calcium binding proteins. The premature loss of interneurons alters inhibitory control over the local neuronal network in favor of net excitation. This effect may explain, for example, why 2 patients who have a similar event (ie, simple febrile convulsion) might have remarkably dissimilar outcomes: One may have completely normal development, and the other may have intractable focal-onset epilepsy after a few years. Mechanisms leading to increased excitation include the following: Increased activation of NMDA receptors Increased synchrony between neurons due to ephaptic interactions Increased synchrony and/or activation due to recurrent excitatory collaterals

Increased activation of NMDA receptors
Glutamate is the major excitatory neurotransmitter in the brain. The release of glutamate causes an EPSP in the postsynaptic neuron by activating the glutaminergic receptors AMPA/kainate and NMDA and the metabotropic receptor. Fast neurotransmission is achieved with the activation of the first 2 types of receptors. The metabotropic receptor alters cellular excitability by means of a second-messenger system with later onset but a prolonged duration. The major functional difference between the 2 fast receptors is that the AMPA/kainate receptor opens channels that primarily allow the passage of monovalent cations (ie, sodium and potassium), whereas the NMDA type is coupled to channels that also allow passage of divalent cations (ie, calcium). Calcium is a catalyst for many intracellular reactions that lead to changes in phosphorylation and gene expression. Thus, it is in itself a second-messenger system. NMDA receptors are generally assumed to be associated with learning and memory. The activation of NMDA receptors is increased in several animal models of epilepsy, such as kindling, kainic acid, pilocarpine, and other focal-onset epilepsy models. Some patients with epilepsy may have an inherited predisposition for fast or long-lasting activation of NMDA channels that alters their seizure threshold. Other possible alterations include the ability of intracellular proteins to buffer calcium, increasing the vulnerability of neurons to any kind of injury that otherwise would not result in neuronal death.

Increased synchrony between neurons due to ephaptic interactions
Electrical fields created by synchronous activation of pyramidal neurons in laminar structures, such as the hippocampus, may increase further the excitability of neighboring neurons by nonsynaptic (ie, ephaptic) interactions. Other possible nonsynaptic interactions include electrotonic interactions due to gap junctions or changes in extracellular ionic concentrations of potassium and calcium. Increased coupling of neurons due to permanent increases in the functional availability of gap junctions might be a mechanism that predisposes to seizures or status epilepticus.

Increased synchrony and/or activation due to recurrent excitatory collaterals
Neuropathologic studies of patients with intractable focal-onset epilepsy have revealed frequent abnormalities in the limbic system, particularly in the hippocampal formation. A common lesion is hippocampal sclerosis, which consists of a pattern of gliosis and neuronal loss primarily affecting the hilar polymorphic region and the CA1 pyramidal region. These changes are associated with relative sparing of the CA2 pyramidal region and an intermediate severity of the lesion in the CA3 pyramidal region and dentate granule neurons. Prominent hippocampal sclerosis is found in about two thirds of patients with intractable temporal-lobe epilepsy. Animal models of status epilepticus reproduced this pattern of injury; however, animals with more than 100 brief convulsions induced by kindling seizures had a similar pattern, suggesting that repeated temporal lobe seizures might contribute to the development of hippocampal sclerosis.[7] A situation more subtle and apparently more common than overt hippocampal sclerosis is mossy-fiber sprouting.[8] The mossy fibers are the axons of the dentate granule neurons, and they typically project into the hilar polymorphic region and toward the CA3 pyramidal neurons. As the neurons in the hilar polymorphic region are progressively lost, their synaptic projections to the dentate granule neurons degenerate. Denervation due to loss of the hilar projection induces sprouting of the neighboring mossy fiber axons. The net consequence of this phenomenon is the formation of recurrent excitatory collaterals, which increase the net excitatory drive of dentate granule neurons.
emedicine.medscape.com/article/1184846-overview#a0104 4/8

7/9/12

Epilepsy and Seizures

Recurrent excitatory collaterals have been demonstrated in human temporal lobe epilepsy and in all animal models of intractable focal-onset epilepsy. The effect of mossy-fiber sprouting on the hippocampal circuitry has been confirmed in computerized models of the epileptic hippocampus. Other neural pathways in the hippocampus, such as the projection from CA1 to the subiculum, have been shown to also remodel in the epileptic brain.

Pathophysiology of Generalized Seizures
The best-understood example of the pathophysiologic mechanisms of generalized seizures is the thalamocortical interaction that may underlie typical absence seizures. The thalamocortical circuit has normal oscillatory rhythms, with periods of relatively increased excitation and periods of relatively increased inhibition. It generates the oscillations observed in sleep spindles. The thalamocortical circuitry includes the pyramidal neurons of the neocortex, the thalamic relay neurons, and the neurons in the nucleus reticularis of the thalamus (NRT). Altered thalamocortical rhythms may result in primarily generalized-onset seizures. The thalamic relay neurons receive ascending inputs from spinal cord and project to the neocortical pyramidal neurons. Cholinergic pathways from the forebrain and the ascending serotonergic, noradrenergic, and cholinergic brainstem pathways prominently regulate this circuitry.[9] The thalamic relay neurons can have oscillations in the resting membrane potential, which increases the probability of synchronous activation of the neocortical pyramidal neuron during depolarization and which significantly lowers the probability of neocortical activation during relative hyperpolarization. The key to these oscillations is the transient low-threshold calcium channel, also known as T-calcium current. In animal studies, inhibitory inputs from the NRT control the activity of thalamic relay neurons. NRT neurons are inhibitory and contain gamma aminobutyric acid (GABA) as their main neurotransmitter. They regulate the activation of the Tcalcium channels in thalamic relay neurons, because those channels must be de-inactivated to open transitorily. T-calcium channels have 3 functional states: open, closed, and inactivated. Calcium enters the cells when the Tcalcium channels are open. Immediately after closing, the channel cannot open again until it reaches a state of inactivation. The thalamic relay neurons have GABA-B receptors in the cell body and receive tonic activation by GABA release from the NRT projection to the thalamic relay neuron. The result is a hyperpolarization that switches the T-calcium channels away from the inactive state into the closed state, which is ready for activation when needed. The switch to closed state permits the synchronous opening of a large population of the T-calcium channels every 100 milliseconds or so, creating the oscillations observed in the EEG recordings from the cerebral cortex. Findings in several animal models of absence seizures, such as lethargic mice, have demonstrated that GABA-B receptor antagonists suppress absence seizures, whereas GABA-B agonists worsen these seizures.[10] Anticonvulsants that prevent absence seizures, such as valproic acid and ethosuximide, suppress the T-calcium current, blocking its channels. One clinical problem is that some anticonvulsants that increase GABA levels (eg, gabapentin, tiagabine, vigabatrin) are associated with an exacerbation of absence seizures. An increased GABA level is thought to increase the degree of synchronization of the thalamocortical circuit and to enlarge the pool of Tcalcium channels available for activation.

Contributor Information and Disclosures
Author Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the eMedicine articles that I wrote or edited. Coauthor(s) Mark Spitz, MD Professor, Department of Neurology, University of Colorado Health Sciences Center Mark Spitz, MD is a member of the following medical societies: American Academy of Neurology, American
emedicine.medscape.com/article/1184846-overview#a0104 5/8

7/9/12

Epilepsy and Seizures

Clinical Neurophysiology Society, and American Epilepsy Society Disclosure: pfizer Honoraria Speaking and teaching; ucb Honoraria Speaking and teaching; lumdbeck Honoraria Consulting Chief Editor Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting Additional Contributors Ramon Diaz-Arrastia, MD, PhD Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, and Phi Beta Kappa Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment

References
1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. Apr 2005;46(4):470-2. [Medline]. 2. Goodkin HP. The founding of the American Epilepsy Society: 1936-1971. Epilepsia. Jan 2007;48(1):15-22. [Medline]. 3. Rho JM, Sankar R, Cavazos JE. Epilepsy: Scientific Foundations of Clinical Practice. New York, NY: Marcel Dekker; 2004. 4. Houser CR, Esclapez M. Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures. Epilepsy Res. Dec 1996;26(1):207-18. [Medline]. 5. Sloviter RS. Status epilepticus-induced neuronal injury and network reorganization. Epilepsia. 1999;40(suppl 1):S34-9; discussion S40-1. [Medline]. 6. Scharfman HE, Schwartzkroin PA. Protection of dentate hilar cells from prolonged stimulation by intracellular calcium chelation. Science. Oct 13 1989;246(4927):257-60. [Medline]. 7. Cavazos JE, Das I, Sutula TP. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci. May 1994;14(5 pt 2):3106-21. [Medline]. 8. Sutula T, Cascino G, Cavazos J, et al. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol. Sep 1989;26(3):321-30. [Medline]. 9. McCormick DA. Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus. J Neurosci. Jan 1992;12(1):278-89. [Medline].
emedicine.medscape.com/article/1184846-overview#a0104 6/8

7/9/12

Epilepsy and Seizures

10. Hosford DA, Clark S, Cao Z, et al. The role of GABAB receptor activation in absence seizures of lethargic (lh/lh) mice. Science. Jul 17 1992;257(5068):398-401. [Medline]. 11. Luders H, Acharya J, Baumgartner C, et al. Semiological seizure classification. Epilepsia. Sep 1998;39(9):1006-13. [Medline]. 12. Loddenkemper T, Kellinghaus C, Wyllie E, Najm IM, Gupta A, Rosenow F. A proposal for a fivedimensional patient-oriented epilepsy classification. Epileptic Disord. Dec 2005;7(4):308-16. [Medline]. 13. Engel J Jr. Report of the ILAE classification core group. Epilepsia. Sep 2006;47(9):1558-68. [Medline]. 14. Wolf P. Basic principles of the ILAE syndrome classification. Epilepsy Res. Aug 2006;70 suppl 1:S20-6. [Medline]. 15. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. Apr 2010;51(4):676-85. [Medline]. 16. Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. Jun 2001;42(6):796-803. [Medline]. 17. Wolf P. Of cabbages and kings: some considerations on classifications, diagnostic schemes, semiology, and concepts. Epilepsia. Jan 2003;44(1):1-4; discussion 4-13. [Medline]. 18. Beghi E. The concept of the epilepsy syndrome: how useful is it in clinical practice?. Epilepsia. May 2009;50 suppl 5:4-10. [Medline]. 19. First Seizure Trial Group (FIR.S.T Group). Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology. Mar 1993;43(3 pt 1):478-83. [Medline]. 20. [Best Evidence] Glauser TA, Cnaan A, Shinnar S, et al, for the Childhood Absence Epilepsy Study Group. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. Mar 4 2010;362(9):790-9. [Medline]. 21. Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. Oct 11 2011;77(15):1473-1481. [Medline]. 22. [Best Evidence] Marson AG, Al-Kharusi AM, Alwaidh M, et al, for the SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. Mar 24 2007;369(9566):1016-26. [Medline]. 23. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. Jul 18 1985;313(3):145-51. [Medline]. 24. Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med. Sep 10 1992;327(11):765-71. [Medline]. 25. [Best Evidence] Rowan AJ, Ramsay RE, Collins JF, et al, for the VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. Jun 14 2005;64(11):1868-73. [Medline]. 26. [Best Evidence] Marson AG, Al-Kharusi AM, Alwaidh M, et al, for the SANAD Study Group. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. Mar 24 2007;369(9566):1000-15. [Medline]. 27. French JA, Kanner AM, Bautista J, et al, for the Therapeutics and Technology Assessment Subcommittee of the AAN; Quality Standards Subcommittee of the AAN; and AES. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. Apr 27 2004;62(8):1252-60. [Medline].
emedicine.medscape.com/article/1184846-overview#a0104 7/8

7/9/12

Epilepsy and Seizures

28. French JA, Kanner AM, Bautista J, et al for the Therapeutics and Technology Assessment Subcommittee of the AAN; Quality Standards Subcommittee of the AAN; and AES. Efficacy and tolerability of the new antiepileptic drugs, II: treatment of refractory epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. Apr 27 2004;62(8):1261-73. [Medline]. 29. [Guideline] Harden CL, Hopp J, Ting TY, et al, for the AAN and AES. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. May 2009;50(5):1229-36. [Medline]. 30. [Guideline] Harden CL, Meador KJ, Pennell PB, et al, for the AAN and AES. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. May 2009;50(5):1237-46. [Medline]. 31. [Guideline] Harden CL, Pennell PB, Koppel BS, et al, for the AAN and AES. Management issues for women with epilepsy--focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. May 2009;50(5):1247-55. [Medline]. 32. Kossoff EH, Turner Z, Bluml RM, Pyzik PL, Vining EP. A randomized, crossover comparison of daily carbohydrate limits using the modified Atkins diet. Epilepsy Behav. May 2007;10(3):432-6. [Medline]. 33. [Best Evidence] Wiebe S, Blume WT, Girvin JP, Eliasziw M, for the Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A randomized, controlled trial of surgery for temporallobe epilepsy. N Engl J Med. Aug 2 2001;345(5):311-8. [Medline]. Medscape Reference © 2011 WebMD, LLC

emedicine.medscape.com/article/1184846-overview#a0104

8/8

Sponsor Documents

Or use your account on DocShare.tips

Hide

Forgot your password?

Or register your new account on DocShare.tips

Hide

Lost your password? Please enter your email address. You will receive a link to create a new password.

Back to log-in

Close