1. Epilepsy and Seizures http://emedicine.medscape.com/article/1184846-overview
Author: Jose E Cavazos, MD, PhD, FAAN; Chief Editor: Selim R Benbadis, MD more...
Updated: Jun 16, 2011
Background
Epileptic seizures are only one manifestation of neurologic or metabolic diseases. Epileptic seizures have many
causes, including a genetic predisposition for certain seizures, head trauma, stroke, brain tumors, alcohol or drug
withdrawal, and other conditions. Epilepsy is a medical condition with recurrent, unprovoked seizures. Therefore,
repeated seizures due to alcohol withdrawal are not epilepsy.
Definitions
As proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) in
2005, epilepsy is defined as a brain disorder characterized by an enduring predisposition to generate epileptic
seizures and by the neurobiologic, cognitive, psychologic, and social consequences of this condition.[1] Traditionally,
the diagnosis of epilepsy requires the occurrence of at least 2 unprovoked seizures 24 hours apart. Some clinicians
are also diagnosing epilepsy when 1 unprovoked seizure occurs in the setting of an interictal discharge. Seizures are
the manifestation of abnormal hypersynchronous discharges of cortical neurons. The clinical signs or symptoms of
seizures depend on the location of the epileptic discharges in the cortex and the extent and pattern of the propagation
of the epileptic discharge in the brain.
It should not be surprising that seizures are a common, nonspecific manifestation of neurologic injury and disease,
because the main function of the brain is the transmission of electrical impulses. The lifetime likelihood of
experiencing at least 1 epileptic seizure is about 9%, and the lifetime likelihood of receiving a diagnosis of epilepsy is
almost 3%. However, the prevalence of active epilepsy is only about 0.8%.
Hauser and collaborators demonstrated that the annual incidence of recurrent nonfebrile seizures in Olmsted County,
Minnesota, was about 100 cases per 100,000 persons aged 0-1 year, 40 per 100,000 persons aged 39-40 years, and
140 per 100,000 persons aged 79-80 years. By the age of 75 years, the cumulative incidence of epilepsy is 3400 per
100,000 men (3.4%) and 2800 per 100,000 women (2.8%).
Studies in several countries have shown incidences and prevalences of seizures similar to those in the United States.
In some countries, parasitic infections account for the increased incidence of seizures and epilepsy.
See Classification of Epileptic Seizures and Classification of Epileptic Syndromes.
Historical information
Epileptic seizures have been recognized for millennia. One of the earliest descriptions of a secondarily generalized
tonic-clonic seizure was recorded over 3000 years ago in Mesopotamia. The seizure was attributed to the god of the
moon. Epileptic seizures were described in other ancient cultures, including those of China, Egypt, and India. An
ancient Egyptian papyrus described a seizure in a man who had previous head trauma. Hippocrates wrote the first
book about epilepsy almost 2500 years ago. He rejected ideas regarding the divine etiology of epilepsy and
concluded that the cause was excessive phlegm that caused abnormal brain consistency. Hippocratic teachings were
forgotten, and divine etiologies again dominated beliefs about epileptic seizures during medieval times. Even at the
turn of the 19th century, excessive masturbation was considered a cause of epilepsy. This hypothesis is credited as
leading to the use of the first effective anticonvulsant (ie, bromides).
Modern investigation of the etiology of epilepsy began with the work of Fritsch, Hitzig, Ferrier, and Caton in the 1870s.
They recorded and evoked epileptic seizures in the cerebral cortex of animals. In 1929, Berger discovered that
electrical brain signals could be recorded from the human head by using scalp electrodes; this discovery led to the
use of electroencephalography (EEG) to study and classify epileptic seizures. Gibbs, Lennox, Penfield, and Jasper
further advanced the understanding of epilepsy and developed the system of the 2 major classes of epileptic seizures
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currently used. An excellent historical review of seizures and epilepsy, written by E. Goldensohn, was published in the
journal Epilepsia to commemorate the 50th anniversary of the creation of the American Epilepsy Society in 1997. A
more recent review discusses the foundation of this professional society.[2]
This article reviews the classifications, pathophysiology, clinical manifestations, and treatment of epileptic seizures and
some common epileptic syndromes. See below for links to several articles related to epileptic syndromes and their
treatment that are not reviewed in this introductory article.
For more information regarding seizure types and other conditions, see the following topics:
Absence Seizures
Complex Partial Seizures
Generalized Tonic-Clonic Seizures
Psychogenic Nonepileptic Seizures
Shuddering Attacks
First Adult Seizure
First Pediatric Seizure
Epilepsia Partialis Continua
Status Epilepticus
Preeclampsia and Eclampsia
See the following articles for more information regarding epileptic syndromes and epilepsy treatment:
Benign Childhood Epilepsy
Benign Neonatal Convulsions
EEG in Common Epilepsy Syndromes
Epileptic and Epileptiform Encephalopathies
Febrile Seizures
Neonatal Seizures
Frontal Lobe Epilepsy
Temporal Lobe Epilepsy
Juvenile Myoclonic Epilepsy
Lennox-Gastaut Syndrome
Posttraumatic Epilepsy
Reflex Epilepsy
Vagus Nerve Stimulation
Women's Health and Epilepsy
Partial Epilepsies
Pediatric Status Epilepticus
Myoclonic Epilepsy Beginning in Infancy or Early Childhood
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 partial-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 Partial Seizures
The clinical neurophysiologic hallmark of partial-onset seizures is the focal interictal epileptiform spike or sharp wave.
The cellular neurophysiologic correlate of an interictal 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.
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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 partial-onset seizures. If the
mechanisms leading to a net increased excitability become permanent alterations, patients may have
pharmacologically intractable partial-onset epilepsy. Currently available medications were developed in acute models
of convulsions. In clinical use, they are most effective at blocking propagation of a seizure. Further understanding of
the mechanisms that permanently increase net excitability may lead to development of true antiepileptic drugs that alter
the natural history of epilepsy.
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 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 available. The reversal potential of chloride is about -70 mV. The contribution of
chloride channels during resting potential in neurons is minimal, because at the typical resting potential, which is near
-70 mV, no significant electromotive force exists 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. Their influence in the neuronal membrane potential increases,
as the neurons become more depolarized by summation of the excitatory postsynaptic potentials (EPSPs).
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
anticonvulsive drug 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 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 described above increase membrane permeability and
conductance of chloride ions. In the end, the behavior of all individual chloride channels sum 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-4-isoxazole
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) appear to be 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
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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).
Changes in the distribution of subunits of the GABA-A receptor complex have been demonstrated in several animal
models of partial-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 a partial-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 by 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
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. Formation of new circuits that include excitatory and inhibitory cells
has been demonstrated in several animal models and in humans with intractable temporal-lobe epilepsy. Insufficient
sprouting that attempts to restore inhibition might alter the balance between excitatory and inhibitory tone in the neural
network.
Defective intracellular buffering of calcium
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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 result showed the critical role of adequate concentrations of calcium-
binding proteins. A postulated contributor is medical intractability in some patients, which may contribute to the
abnormally low concentrations or even dysfunction of these proteins.
The end result is the premature loss of interneurons, which 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 (eg, simple febrile
convulsion) have remarkably dissimilar outcomes: One may have completely normal development, and the other may
have intractable partial-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 first 2 types. The metabotropic receptor alters cellular excitability
by means of a second-messenger system with late onset but 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 status, pilocarpine, and other 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 synchrony and/or activation due to recurrent excitatory collaterals
Neuropathologic studies of patients with intractable partial-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 lesion in the CA3
pyramidal region with dentate granule cells. 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.[7]
A situation more subtle and apparently more common than that described above is mossy-fiber sprouting.[8] Mossy
fibers are the axons of the dentate granule cells and typically project into the hilar polymorphic region and the CA3
pyramidal neurons. As neurons in the hilar polymorphic region are lost, their feedback projection into the dentate
granule cells degenerates. 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.
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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 (eg, in sleep spindles). The 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 T-calcium 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
T-calcium 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, permitting the synchronous opening of a large population of the
T-calcium channels every 100 milliseconds or so.
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 T-calcium
channels available for activation.
Prognosis
The patient's prognosis for disability and for a recurrence of epileptic seizures depends on the type of epileptic
seizure and the epileptic syndrome in question.
Regarding morbidity, trauma is not uncommon among people with generalized tonic-clonic seizures. Injuries such as
ecchymosis; abrasions; and tongue, facial, and limb lacerations often develop as a result of the repeated tonic-clonic
movements. Atonic seizures are also frequently associated with facial and neck injuries. Worldwide, burns are the
most common serious injury associated with epileptic seizures.
Regarding mortality, seizures cause death in a small proportion of individuals. Most deaths are accidental due to
impaired consciousness. However, sudden unexpected death in epilepsy (SUDEP) may occur even when patients are
resting in a protected environment (eg, in a bed with rail guards).
The incidence of SUDEP is low, about 2.3 times higher than the incidence of sudden death in the general population.
The difference is mostly related to people with long-standing partial-onset epilepsy. The risk of SUDEP rises in people
with uncontrolled seizures and probably in people with poor compliance. The risk increases further in people with
uncontrolled secondarily generalized tonic-clonic seizures.
The mechanism of death in SUDEP is controversial, but suggestions include cardiac arrhythmias, pulmonary edema,
and suffocation during an epileptic seizure with impairment of consciousness. Treatment with anticonvulsants
decreases the likelihood of an accidental seizure-related death.
Patient Education
To prevent injury, educate patients who have lapses of consciousness during wakefulness and in whom seizures are
suspected about seizure precautions. Most accidents occur when patients have impaired consciousness. This is one
of the reasons for restrictions on driving, swimming, taking unsupervised baths, working at significant heights, and the
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use of fire and power tools in people who have epileptic seizures and other spells of sudden-onset seizures.
The restrictions differ for each patient because of the individual features of the seizures; the degree of seizure control;
and, in the United States, state laws. Other countries have more permissive or more restrictive laws regarding driving.
Epilepsy Foundation of America has a large library of educational materials that are available to health care
professionals and the general public. The American Epilepsy Society is the professional organization of people who
take care of patients with epilepsy. Their Web site provides a large amount of credible information.
For patient education information, see the Brain and Nervous System Center, as well as Epilepsy and Seizures
Emergencies.
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 Clinical
Neurophysiology Society, and American Epilepsy Society
Disclosure: pfizer Honoraria Speaking and teaching; ucb Honoraria Speaking and teaching; lumdbeck Honoraria
Consulting
Specialty Editor Board
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
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
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