Epilepsy Principles and Diagnosis

Epilepsy Board Review Manual
Statement of
Editorial Purpose
The Epilepsy Board Review Manual is a study
guide for trainees and practicing physicians
preparing for board examinations in epilepsy.
Each manual reviews a topic essential to the
current management of patients with epilepsy.
Seizures and Epilepsy:

Pathophysiology and
Principles of Diagnosis
Contributor and Editor:
Thomas R. Henry, MD
PUBLISHING STAFF
Professor of Neurology, Director, Comprehensive Epilepsy

Center, University of Minnesota Medical School,
Minneapolis, MN
PRESIDENT, Group PUBLISHER
Bruce M. White
Senior EDITOR
Robert Litchkofski
executive vice president
Barbara T. White
executive director
of operations
Jean M. Gaul
Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Nature of Epileptic Seizures and Epilepsies . . . . 2
Classification of Seizures. . . . . . . . . . . . . . . . . . . 4
History, Examination, and Laboratory Tests. . . . 7
Classification of Epilepsies and Epileptic
Seizures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Specific Syndromes of Epilepsy. . . . . . . . . . . . . 10
NOTE FROM THE PUBLISHER:

This publication has been developed with
out involvement of or review by the Amer
ican Board of Psychiatry and Neurology.
Board Review Questions. . . . . . . . . . . . . . . . . . . 21

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Epilepsy and Seizures: Pathophysiology and Diagnostic Principles
Epilepsy Board Review Manual
Seizures and Epilepsy:

Pathophysiology and Principles of Diagnosis
Thomas R. Henry, MD
Introduction
Epileptic seizures are among the most common
neurologic symptoms in all human populations.
Over 5% of Americans have at least one epileptic
seizure during their lifetimes.1 At any point in time,
1% to 2% of Americans have epilepsy. Cumulative
lifetime incidence of epilepsy exceeds 3%. These
statistics are similar across large human populations, although the incidence and prevalence of
epileptic seizures and epilepsies can be higher in
certain smaller groups (for example, in populations
exposed to military combat due to high rates of traumatic brain injury [TBI]).
This article is the first of a 6-part review of epilepsy
diagnosis and management. It provides an overview
of the pathophysiology of epileptic seizures and classification systems for seizure and epilepsy and summarizes key features of established types of epilepsies. Subsequent articles in this series will discuss the
techniques, interpretation, and applications of electroencephalography (EEG) and video-EEG (Part 2)
and structural and functional brain imaging (Parts 3
and 4). Part 5 focuses on selection, dosing, adverse
effects, and therapeutic monitoring of antiseizure

medications. Part 6 will review both epilepsy surgery,
including the role of neuropsychological testing in
planning for epilepsy surgery,2 and the application
of neuropsychological testing in initial diagnosis and
rehabilitaton of patients with epilepsy.
definitions
Seizures are defined as paroxysmal events of
transitory alteration in consciousness or other signs
or symptoms that can be due to brain dysfunction.
Epileptic seizures are seizure events that are caused
by excessive, abnormally synchronized, localized or
widely distributed neuronal electrical discharges3;
usually these electrophysiological correlates are
presumed by indirect evidence, although electrophysiological recordings sometimes are performed
during seizures. Nonepileptic seizures are seizure
events that are not caused by such electrocerebral
discharges. Nonepileptic seizures are sometimes
divided into categories of organic nonepileptic seizures, such as atypical syncope and parasomnias,
and psychogenic nonepileptic seizures, such as
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www.turner-white.com Epilepsy Volume 1, Part 1 1
Figure 1. Paroxysmal depolarization shift (PDS). When a PDS occurs as an abnormally prolonged run of action potentials during sustained
membrane depolarization in a single neuron, as shown in the upper trace in B, the event is detectable only with microelectrodes; increased
glutamate concentration is associated with influx of cations initially, followed by increased GABA concentration with efflux of potassium.
When PDSs in a large number of neurons are synchronized for less than 200 ms, as shown in A, these electrical potentials may summate
as a spike-wave complex that is recorded with macroelectrodes, as shown in the lower trace in B. When sustained repetitive firing of PDSs
in a large number of neurons becomes synchronized for many seconds or longer, an electrographic seizure occurs, as shown in C. (Adapted
with permission from Holmes GL, Ben-Ari Y. Seizing hold of seizures. Nature Med 2003;9:9946.)
conversion symptoms and dissociative states. Many

clinicians use terms such as spell or event to
help the patient more clearly understand that these
are not epileptic seizures.
Epilepsy is a condition in which persisting cerebral dysfunction causes recurring epileptic seizures
without the need for immediate insults to provoke
each seizure2; exacerbants such as sleep deprivation can increase seizure frequency in epilepsy,
however. Acute symptomatic seizures are generalized tonic-clonic seizures that occur in the absence
of epilepsy in response to a wide range of provoking
insults, such as hyponatremia and other electrolyte
disorders and fever in infants and young children.3
Nature of epileptic seizures and

epilepsies
Neurobiology of epileptic seizures
The paroxysmal depolarization shift (PDS) is

the pathophysiological cellular phenomenon that
2 Hospital Physician Board Review Manual
underlies all types of epileptic seizures (Figure 1)

and interictal epileptiform electroencephalography (EEG) abnormalities (spikes).5,6 PDSs are
cellular events in which rapidly repetitive action
potentials are not followed by the usual refractory
period, thereby generating a prolonged membrane depolarization (which is more prolonged
than typically occurs in response to normal excitatory postsynaptic potentials [EPSPs]). An interictal spike is caused by PDSs in large numbers
of neurons that are synchronized such that each
involved neuron generates one PDS at the same
time. An electroclinical seizure occurs when large
numbers of neurons in one or more brain regions
are repeatedly generating PDSs, in sustained
repetitive firing with synchronization. Repetitive
neuronal firing probably underlies the interictal
and ictal unit and local field recording of highfrequency oscillations.7
The tendency of individual neurons to enter
pathological states in which PDSs are generated
www.turner-white.com
Figure 2. Genetic channelopathies in epilepsy. (A) Genetic channelopathies can support the occurrence of paroxysmal depolarization shifts (PDS) by altering the usual balance of Na+ and K+ ion conductance across neuronal membranes. Increased Na+
conductance (B, upper panel) creates a situation in which a single action potential initiates sustained depolarization as a PDS
(B, lower panel). Decreased K+ conductance (C, upper panel) also can predispose to PDS. (Adapted with permission from Chang
BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1261. Copyright 2003 Massachusetts Medical Society.)
can be based on intrinsic neuronal properties,

such as dysfunctional ionophores in the genetically determined channelopathies (Figure 2), or
on extrinsic mechanisms such as inadequate
inhibitory neurotransmitter concentrations or exposure to excessive concentrations of excitatory
amino acids or exogenous excitotoxins. However,
large groups of neurons must generate PDSs simultaneously to account for the episodic nature of
seizures. In experimental models of generalized
epilepsies, this widespread epileptic synchronization of interictal and ictal PDSs is based on
intrathalamic synchronization that drives thalamocortical relay neurons to synchronize the bihemispheric cortical neuronal discharges (Figure 3).8
In experimental models of partial epilepsies, intracortical mechanisms of synchronization operate during ictal discharges (Figure 4).8 There is
evidence that in certain epilepsies specific channelopathies operate to initiate PDSs in individual
neurons and produce seizures through normal
mechanisms of interneuronal synchronization,
while other epilepsies appear to require abnormal
interneuronal pathways to generate pathological
synchronization.
Experimental models of seizures and
epilepsy
Experimentally induced seizures and animal

models of epilepsy have been used extensively to
Figure 3. Thalamocortical circuits in generalized epilepsies. Under normal conditions, brainstem monoaminergic projections synchronize
the thalamic reticular neurons into cycles of slow waves, and GABAergic projections of these neurons synchronize thalamocortical relay
neurons into cycles of slow waves, resulting in synchronized glutamatergic thalamocortical projections to widespread cortical areas that
generate the electroencephalography (EEG)-recorded slow waves of non-REM sleep and also sleep spindles. In generalized epilepsies,
repetitive paroxysmal depolarization shifts (PDSs) in thalamic reticular neurons synchronize PDSs in thalamocortical relay neurons, which
in turn synchronize PDSs in cortical neurons, thus generating EEG-recorded spike-wave discharges and sometimes absence seizures.
Presumably, a structurally normal complement of thalamic and cortical neurons and their pathways are able to generate spike-wave discharges and absence seizures due to genetically based dysfunction of channels, receptors, or other neurochemical elements. (Adapted with
permission from Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1259. Copyright 2003 Massachusetts Medical Society.)
study the nature of seizures and epilepsy and to

develop new therapies for epilepsy.9 For much of
the 20th century, potential new antiseizure medications were tested in rodents with the maximal
electroshock model and the pentylenetetrazole
model. Most experimental epilepsy research has
been performed with acute seizure and epilepsy preparations, although amygdala kindling
and post-status epilepticus models offer chronic
epilepsy models, as do genetic rodent models of

epilepsy.
Classification of seizures
Types of epileptic seizures
The starting point in diagnosis of seizures and

epilepsy is to determine the type(s) of seizures
that the individual has sustained, or at least
Figure 4. Epilepsy pathophysiology in mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis. Epileptic reorganization of the
hippocampal formation can be caused by a variety of insults that cause loss of vulnerable neurons in experimental models, but etiologic
insults only occasionally are evident in human TLE. This epileptic reorganization includes sprouting of mossy-fiber axons of dentate
granule cells; dentate granule cells project to CA3 neurons, and increased activity in mossy-fiber projections can support excessive
excitation of CA3 neurons. Thus, according to this hypothesis, normal excitatory inputs from the entorhinal cortical neurons to these
reorganized dentate granule cells induce excessive excitation of CA3 neurons in the setting of inadequate inhibition, to initiate sustained
repetitive firing in downstream CA1 neurons as a focal seizure with the potential to propagate more widely. Several experimental models
of TLE generate the same histopathological findings in the animal hippocampus that are observed in the human hippocampal sclerosis.
(Adapted with permission from Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1262. Copyright 2003 Massachusetts
Medical Society.)
generate a hypothesis regarding the type(s) of

seizures. Consensus by experts of the International League Against Epilepsy (ILAE) established an electroclinical classification of seizure
types (Table 1) that has been widely used for
over 3 decades.10 A new classification of seizures
proposed by the ILAE (Table 2) is similar to the
earlier classification with regard to generalizedonset seizures, but the new classification abolished the subtypes of partial-onset seizures,
instead considering altered awareness and generalized convulsive activity to be descriptors for
focal seizures with evolution into generalized
convulsive activity.
Types of nonepileptic seizures
Organic nonepileptic seizures are paroxysmal

events caused by a nonepileptic condition. These
events are grouped as nonepileptic seizures mainly
because they can mimic epileptic seizures, not
because they have a common pathophysiology.
Seizures caused by other organic conditions usually are confused with epileptic seizures because
patients cannot describe their own behaviors during events that cause loss of consciousness, and
because witnesses usually can provide only limited
information about behaviors during the events.11
(In contrast, expert review of ictal behaviors on
video-EEG recordings affords detailed and accurate

Table 1. ILAE 1981 Classification of Seizures
I. Partial (focal, localization-related) seizures
A. Simple partial seizures
1. With motor signs
2. With somatosensory or special-sensory symptoms
3. With autonomic symptoms or signs
4. With psychic symptoms
B. Complex partial seizures
1. With impairment of consciousness at onset
2. Simple partial onset followed by impairment of consciousness
C. Partial seizures with secondary generalization
1. With simple partial seizures evolving to generalized seizures
2. With complex partial seizures evolving to generalized seizures
3. With simple partial seizures evolving to complex partial
seizures evolving to generalized seizures
II. Generalized seizures
A. Absence seizures
1. With impairment of consciousness only
2. With mild clonic components
3. With atonic components
4. With tonic components
5. With automatisms
B. Myoclonic seizures
C. Clonic seizures
D. Tonic seizures
E. Tonic-clonic seizures
F. Atonic (astatic) seizures
Adapted with permission from Proposal for revised clinical and electrographic classification of epileptic seizures. From the Commission
on Classification and Terminology of the International League Against
Epilepsy. Epilepsia 1981;22:489501.
information regarding movements and responsiveness.) For example, when syncope is not preceded
by lightheadedness and postsyncopal confusion
occurs, other diagnoses must be entertained. Atypical presentations of syncope and incompletely observed parasomnias are among the most common
organic nonepileptic seizures.12,13
Psychogenic nonepileptic seizures (PNES) can
mimic essentially any type of epileptic seizure, as
described to the neurologist by the patient and

lay observers of the seizure events.14,15 Recording
of habitual events on video-EEG not only shows
absence of electrocerebral discharges of types expected for epileptic seizures with similar behaviors,
but also provides an opportunity for detailed analysis of the behaviors themselves. Specific psychiatric syndromes do not appear to have relationships
with patterns of event behaviors. Current understandings of PNES is that conversion-type reactions and dissociative states are not under direct
conscious control, and these represent the majority of PNES. Conversion-type PNES can occur in
individuals with persisting somatiform disorders
who have evidence of other nonorganic dysfunctions, but many conversion-type PNES occur in
isolation. Dissociative-state PNES often occur in
individuals with a history of physical, sexual, or
other abuse in the setting of post-traumatic stress
disorder; this group of PNES patients may be the
most responsive to cognitive-behavioral forms of
psychological therapy. While malingering with
consciously controlled events of unresponsiveness can occur, this scenario appears to be rather
uncommon as a cause of repeated PNES. Many
epileptologists who diagnose PNES routinely refer
for psychiatric consultation first, to be certain that
additional psychiatric diagnoses are not missed,
and next to a clinical psychologist for therapy.
Table 3 summarizes the commonly encountered
types of nonepileptic seizures that cause loss of
consciousness or an event with unresponsiveness
and subsequent amnesia for the event, together
with epileptic seizure types, descriptions of motor
behaviors at the level of detail usually achieved by
nonmedical witnesses of seizures, and typical diagnostic tests. Transitory events without impaired
awareness have very different diagnostic considerations, which include simple partial epileptic

seizures, a large range of organic movements
(including dystonias, tics, positional clonus, and
blepharospasm), a very large range of organic subjective sensations and experiences (including vertigo, tinnitus, and abdominal sensations), a large
array of psychogenic movements, and an even
larger array of psychogenic sensations-perceptions
and mental experiences. Frequently recurring movements without loss of consciousness often can
be video-recorded to diagnose movements that
fit established patterns of movement disorders or
other organic conditions; however, care must be
taken not to equate bizarreness of movements with
psychogenicity, given the propensity of frontal lobe
epilepsies and REM behavior disorders to cause
peculiar movements. In general, the laboratory
tests listed in Table 3 are more likely to provide
definitive diagnostic evidence for the nature of
transitory events that are associated with impaired
consciousness, or at least with abnormal movements, than they are for transitory events during
which baseline responsiveness is maintained.
Table 2. ILAE 2010 Classification of Seizures

I. Focal seizures
Descriptors of focal seizures:
A. Without impairment of consciousness or awareness
1. With observable motor or autonomic components
2. Involving subjective sensory or psychic phenomena only
B. With impairment of consciousness or awareness
C. Evolving to a bilateral, convulsive seizure
II. Generalized seizures
A. Tonic-clonic seizures
B. Absence seizures
1. Typical
2. Atypical
3. Absence with special features
a. Myoclonic absence
b. Eyelid myoclonia
C. Myoclonic
1. Myoclonic
2. Myoclonic atonic
3. Myoclonic tonic
D. Clonic
E. Tonic
F. Atonic
G. Unknown
1. Epileptic spasms
History, examination, and laboratory

tests
Adapted with permission from 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 2010;51:67685.
The common risk factors, historical associations,

and examination findings for epileptic seizures are
listed in Table 4. The risk factors for nonepileptic
seizures generally differ from those for epileptic seizures, including prior history of hysteriform paralyses or movements and prior history of childhood
sexual abuse or other psychological trauma. An
important exception is TBI, which is highly associated with both epilepsy and psychogenic seizures.
Potentially epileptogenic insults usually should
have occurred months or years before onset of the
habitually recurring epileptic seizures, giving rise to
the typical temporal pattern of an initial precipitat-
ing event followed by a latent period (during which

the epileptic seizures have not yet begun to occur)
and lastly the phase of active epilepsy. Epileptic
seizures that occur during or within a week after
a cerebral or systemic insult are generally considered provoked seizures that are not indicative of
epilepsy. Among the exceptions to these patterns
are conditions in which seemingly unprovoked
forms of status epilepticus occur at onset of a condition that later manifests as sporadically recurrent
seizures, such as the hemiconvulsion-hemiplegia-

Table 3. Epileptic and Nonepileptic Seizures with Impaired Awareness, Listed by Predominant Motor Activities During Seizures
Predominant Motor Phenomena as Described by Witnesses of Seizures
Movements during period

of unresponsiveness
Epileptic seizure types
Convulsion
Hypopostural Event
Bilateral, repetitive, rapid

flexion-extension, jerking or shaking movements
Generalized tonic-clonic
Generalized clonic
Sudden fall or droop, without jerking or shaking
Organic nonepileptic
event types
Rigors
Psychogenic nonepileptic
seizure types
Most frequently indicated
tests
Psychogenic convulsion
Generalized tonic
Generalized atonic
Generalized myoclonic
Infantile spasm
Syncope
Vertebrobasilar TIA
Cataplexy
Psychogenic swoon
EEG or video-EEG,
routine or prolonged
Brain MRI
(CT emergently)
ECG, routine or
prolonged
Tilt-table test
Brain MRI/MRA
Event with Automatisms Motionless Event

(Staring Spell)
Staring spell, with moveStaring spell, without jerkments more complex
ing, fall, or other moveand localized than jerkments
ing or fall
Complex partial
Complex partial
Atypical absence
Typical absence
REM behavior disorder

Somnambulism and other
parasomnias
Atypical arousal
Psychogenic fugue state
Psychogenic stare or
catatonia
EEG or video-EEG,
Brain MRI
EEG or video-EEG,
Brain MRI
Polysomnography
CT = computed tomography; ECG = electrocardiography; EEG = electroencephalography; MRA = magnetic resonance angiography; MRI = magnetic
resonance imaging; TIA = transient ischemic attack.
Adapted with permission from Henry TR, Drury I. Non-epileptic seizures in temporal lobectomy candidates with medically refractory seizures.
Neurology 1997;48:137482
epilepsy syndrome (see Heconvulsion-HemiplegiaEpilepsy section below).

Brief, interictal EEG recordings with scalp electrodes (routine EEGs) can record interictal epileptiform activities (spikes) and nonepileptiform abnormalities. Interictal spikes are valuable signs of
epileptic excitability.16 In most epilepsies, interictal
spikes can occur intermittently, such that prolonged
EEG recordings often detect spikes missed with
routine EEGs. Ambulatory EEG can detect interictal spikes and electrographic seizures that occur
infrequently.17 Focal interictal spikes tend to occur in
partial epilepsies, and generalized interictal spikes
often occur in generalized epilepsies, but exceptions to this principle are common. Normal interictal
EEGs are common in many epilepsies, as are interictal focal and generalized slowing without spikes.
Video-EEG monitoring is highly valuable in diagnosis of paroxysmal events with impaired consciousness or with abnormal movements and behaviors.18
The EEG data can fully distinguish epileptic seizure
discharges (with phenomena specific to partialonset versus generalized-onset epileptic seizures),
pathological generalized slowing and depression of
electrocerebral activities (of syncope and organic
encephalopathies), onset of unconscious behaviors
during sleep (specific to REM-onset versus slowwave sleep onset), and absence of change from
waking or drowsy baseline EEG activities (in psychogenic events). The synchronized audio-video recordwww.turner-white.com

Table 4. Summary of Risk Factors, Historical Associations, and Examination Findings for Diagnosis of Epileptic Syndromes
Risk factors and historical associations often provided by the patient or lay care givers:
Family history of epilepsy or seizures
Family history of genetic conditions that are potentially epileptogenic in family members without seizures (eg, neurofibromatosis type 1)
History of gestational or perinatal injury, febrile convulsions, developmental delay, stroke, meningitis, encephalitis, significant traumatic
brain injury, ethanol or other drug abuse, or other epileptic predispositions
Reported seizure-provoking factors: photic stimulation-flashing lights, hyperventilation, sleep deprivation, ethanol use or cessation, use of
carbamazepine or other antiseizure medications known to exacerbate specific epileptic seizure types, catamenial exacerbation, numerous other possible seizure triggers and exacerbants
Risk factors and historical associations often provided by the medical chart (eg, previously diagnosed clinical-imaging conditions)
and conditions which the epileptologist will find on further evaluation:
Primary or metastatic cerebral neoplasm (glioblastoma and lower-grade glial tumors, ganglioglioma and gangliocytoma, dysembryoplastic
neuroepithelial tumor, others)
Primary or metastatic extra-axial, intracranial neoplasm (meningioma, meningeal carcinomatosis, others)
Cerebral infarction or hemorrhage, chronic (including residua of posterior reversible encephalopathy syndrome)
Cerebral infection, remote or chronic (including cysticercosis, bacterial-mycobacterial-fungal cerebritis or abscess, bacterial meningitis,
herpes or other viral encephalitis, retroviral encephalopathy, prion disease, others)
Post-traumatic encephalomalacia (particularly with retained skull or metal fragment or hemosiderin deposition)
Cerebrovascular lesion (arteriovenous malformation, cavernoma)
Malformation of cortical development (lissencephaly, schizencephaly, hemimegalencephaly, perisylvian or other polymicrogyria, band or
nodular heterotopia, focal cortical dysplasia, others)
Genetic disorders of neurocognitive development (Aicardi syndrome, fragile X syndrome, Angelman syndrome, Rett syndrome, Down
syndrome, trisomy 12p, ring 20 chromosome syndrome, Alpers disease, progressive encephalopathy with edema-hypsarrhythmia-optic
atrophy [PEHO syndrome], others)
Inherited metabolic disorders (mitochondrial diseases including pyruvate dehydrogenase deficiency and MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], neuronal storage disorders including Lafora disease and neuronal ceroid lipofuscinosis, peroxisomal disorders, cerebral calcinosis due to celiac disease, glycine encephalopathy, propionic acidemia and other organic
acidurias, pyridoxine dependency, phenylketonuria and other aminoacidopathies, urea cycle disorders, disorders of carbohydrate metabolism, disorders of biotin, folate, or B12 metabolism, glucose transporter protein deficiency, Menkes disease, glycogen storage disorders,
Krabbe disease, fumarase deficiency, Sanfilippo syndrome)
Neurodegenerative conditions of adult onset (Alzheimer disease, Huntington disease, others)
Neurodegenerative conditions due to neurotoxin exposure (organic solvents, lead, mercury, others)
Other cerebral conditions of adult onset (eg, multiple sclerosis, neurosarcoidosis, sequelae of lupus cerebritis, sequelae of paraneoplastic
limbic encephalitis)
Other encephalopathies of unknown etiology (eg, autism and other developmental syndromes, neuropsychiatric encephalopathies of later
onset including schizophrenia).
Neurosurgical instrumentation (eg, ventricular shunt, deep-brain stimulation electrode)
Examination findings
Cutaneous stigmata of phakomatosis or neurocutaneous syndrome (adenoma sebaceum, ash leaf spots, shagreen patches, or periungual
fibromas of tuberous sclerosis, multiple large caf-au-lait spots or axillary freckling of neurofibromatosis, facial angioma of encephalotrigeminal angiomatosis, others)
Oculoretinal stigmata of storage disorders (cherry red spot of sialidosis, iris hamartoma of neurofibromatosis, others)
Craniofacial dysmorphism of neurodevelopemenal syndromes (Down syndrome, others)
Cranial defects suggesting unreported trauma or neurosurgical intervention
Static abnormalities of the neurological examination indicating cognitive deficits, psychosis, and cerebral motor or sensory dysfunction
Episodic abnormalities of the neurological examination including interictal spontaneous or startle-induced myoclonus and witnessed ictal
manifestations

ing of behaviors is highly informative, and even when
myogenic and kinesigenic artifacts obscure the EEG
recording, the recorded behavioral data frequently in
itself supports definitive seizure diagnosis.
Classification of epilepsies and

epileptic syndromes
1989 classification
There are many highly individual aspects of the

seizures, interictal dysfunctions, and associated cerebral and systemic conditions experienced by persons with epilepsy. Nonetheless, it is obvious that
some of these characteristics cluster across individuals as particular types of epilepsy. Ideally, every
person with epilepsy could be assigned to one type
of epilepsy, and the various types of epilepsy could
be classified into a neurobiologically based, clinically relevant organizational schema of the epilepsies.
This ideal taxonomy of the epilepsies has yet to be
devised, and clinical epileptologists must use the
current epilepsy classifications to guide diagnostics
and therapeutics.
At this time, the most widely accepted classification of epilepsy types is that published by
the ILAE in 1989 (Table 5).19 In addition to defining accepted epilepsy types, this taxonomy used
2 dichotomous principles to organize the epilepsy
types. The partial (or focal, or localization-related)
versus generalized dichotomy was determined by
whether the individual had partial-onset or generalized-onset seizures, respectively. The idiopathic (or
primary) versus symptomatic (or secondary, or acquired) dichotomy was determined by whether the
individual had seizure intrinsic to his or her brain
structure-function in the absence of any brain insult,
or had a brain insult that precipitated epileptogenesis, respectively. A special category of the symptomatic group was persons with seizures of cryptogenic
etiology who had indirect evidence of having had

a causative brain insult, although the precise insult
could not be determined. Characteristically, the idiopathic epilepsies had no interictal evidence of brain
injury, so interictal intelligence and other functions
typically are normal or nearly normal. Symptomatic
partial epilepsies often feature interictal dysfunctions localized to the injured area, which includes
the ictal onset zone, with mental retardation or developmental delay in many of those with symptomatic generalized epilepsies (eg, delayed verbal recall
deficits in those with left-sided mesial temporal lobe
epilepsy-hippocampal sclerosis, a symptomatic and
usually cryptogenic partial epilepsy).
2010 classification
Ongoing efforts to improve epilepsy classification

were most recently summarized in 2010 (Table 6).20
The partial-generalized and idiopathic-cryptogenic
dichotomies were discarded, and the epilepsy types
were organized by typical developmental stage at
seizure onset (eg, neonatal, childhood) and etiology. The established types of epilepsy are mainly
the same as those recognized by the 1989 classification, although more developed and specific
syndromes of neonatal seizure onset are included
in the 2010 classification. The new epilepsy classification has been described as multifactorial and
flexible, with emphases on age at onset and etiology, and also as a work-in-progress and incomplete.
Epileptologists will need to track this transitional period in epilepsy classification systems, but fortunately the core knowledge of classification continues to
be in recognition of the individual epilepsy types.
Specific syndromes of epilepsy

A number of epilepsies are established as clinically distinguishable from epilepsy as a whole, with

Table 5. ILAE 1989 Classification of Epilepsies
1. Localization-related (focal, local, partial) epilepsies and syndromes
1.1 Idiopathic (with age-related onset)
Benign childhood epilepsy with centrotemporal spikes
Childhood epilepsy with occipital paroxysms
Primary reading epilepsy
1.2 Symptomatic
Chronic progressive epilepsia partialis continua of childhood (Kojewnikow syndrome)
Syndromes characterized by seizures with specific modes of precipitation
Temporal lobe epilepsies (amygdalo-hippocampal, lateral temporal)
Frontal lobe epilepsies (supplementary motor, cingulate, anterior frontopolar, orbitofrontal, dorsolateral, opercular, motor cortex)
Parietal lobe epilepsies
Occipital lobe epilepsies4
1.3 Cryptogenic (same syndromes as for symptomatic localization-related epilepsies, but without known etiology)
2. Generalized epilepsies and syndromes
2.1 Idiopathic (with age-related onset)
Benign neonatal familial convulsions
Benign neonatal convulsions
Benign myoclonic epilepsy in infancy
Childhood absence epilepsy (pyknolepsy)
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Epilepsy with grand mal (GTCS) seizures on awakening
Other generalized idiopathic epilepsies not defined above
Epilepsies with seizures precipitated by specific modes of activation
2.2 Cryptogenic or symptomatic
West syndrome
Lennox-Gastaut syndrome
Epilepsy with myoclonic-astatic seizures
Epilepsy with myoclonic absences
2.3 Symptomatic
2.3.1 Nonspecific etiology
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy with suppression burst
Other symptomatic generalized epilepsies not defined above
2.3.2 Specific syndromes
Epileptic seizures that complicate a specific disease state
3. Epilepsies and syndromes undetermined whether focal or generalized
3.1 With both generalized and focal seizures
Neonatal seizures
Severe myoclonic epilepsy in infancy
Epilepsy with continuous spike-waves during slow wave sleep
Acquired epileptic aphasia (Landau-Kleffner syndrome)
Other undetermined epilepsies not defined above
3.2 Without unequivocal generalized or focal features. All cases with generalized tonic-clonic seizures in which clinical and EEG findings
do not permit classification as clearly generalized or localization related, such as in many cases of sleep grand mal (GTCS) are considered not to have unequivocal generalized or focal features.
4. Special syndromes
4.1 Situation-related seizures (Gelegenheitsanflle)
Febrile convulsions
Isolated seizures or isolated status epilepticus
Seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia, nonketotic
hyperglycemia
Adapted with permission from Proposal for revised classification of epilepsies and epileptic syndromes. From the Commission on Classification
and Terminology of the International League Against Epilepsy. Epilepsia 1989;30:38999.

Table 6. ILAE 2010 Proposal for Classification of Epilepsies
Organizational Group
Neonatal onset group
Infancy onset group
Childhood onset group
Adolescence Adult
Less specific age relationship

Distinctive constellations
Epilepsies that do not fit into any of these diagnostic categories

Epilepsies attributed to and organized by structural-metabolic causes
Epilepsies of unknown cause
Conditions with epileptic seizures that are traditionally not diagnosed
as a form of epilepsy per se
Electroclinical Syndrome
Benign familial neonatal epilepsy (BFNE)
Early myoclonic encephalopathy (EME)
Early myoclonic encephalopathy (EME)
Epilepsy of infancy with migrating focal seizures
West syndrome
Myoclonic epilepsy in infancy (MEI)
Benign infantile epilepsy
Benign familial infantile epilepsy
Dravet syndrome
Myoclonic encephalopathy in nonprogressive disorders
Febrile seizures plus (FS+) (can start in infancy)
Panayiotopoulos syndrome
Epilepsy with myoclonic atonic (previously astatic) seizures
Benign epilepsy with centrotemporal spikes (BECTS)
Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)
Late onset childhood occipital epilepsy (Gastaut type)
Epilepsy with myoclonic absences
Lennox-Gastaut syndrome
Epileptic encephalopathy with continuous spike-and-wave during
sleep (CSWS)
Landau-Kleffner syndrome (LKS)
Childhood absence epilepsy (CAE)
Juvenile absence epilepsy (JAE)
Juvenile myoclonic epilepsy (JME)
Epilepsy with generalized tonicclonic seizures alone
Progressive myoclonus epilepsies (PME)
Autosomal dominant epilepsy with auditory features (ADEAF)
Other familial temporal lobe epilepsies
Familial focal epilepsy with variable foci (childhood to adult)
Reflex epilepsies
Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS)
Rasmussen syndrome
Gelastic seizures with hypothalamic hamartoma
Hemiconvulsionhemiplegiaepilepsy
Benign neonatal seizures (BNS)

Febrile seizures (FS)
Adapted with permission from 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 2010;51:67685.
diagnostic criteria by (1) seizure types, (2) age

at onset, and (3) EEG and imaging findings, and
in many instances supplemented by information
regarding (4) associated cerebral and systemic

conditions, (5) interictal cerebral dysfunctions, and
(6) typical responses to specific medications or

other therapies that had been used before the current attempt to diagnose the individuals epilepsy
type. Successful classification of epilepsy type
usually supports the physician's efforts to establish a prognosis regarding remission of active epilepsy. Many individual patients have epilepsy with
specific seizure types but lack other information
that permits diagnosis of an established epilepsy
syndrome. When seizure types can be diagnosed
but the overall epilepsy cannot be classified, the
physician's ability to make an accurate prognosis
is limited. The following list of epileptic syndromes
is derived from the current ILAE consensus on
classification,20 grouped by age at seizure onset.
Neonatal period
Benign familial neonatal epilepsy (BFNE)

is an autosomal dominant condition in which
brief (12 sec) generalized events include tonic,
apneic, and other features.2124 Seizures usually
begin within the first days after birth and remit in
over 80% within the first 6 weeks. Those whose
seizures do not remit may have a few seizures in
adulthood. Several potassium channelopathies appear to be responsible for BFNE. The prognosis for
neurocognitive development is good.
Early myoclonic encephalopathy (EME) is
a neonatal syndrome with frequent myoclonia
and focal motor seizures and is associated with
a burstsuppression pattern on EEG.2527 Various
metabolic syndromes are the most common etiologies. Some children with EME recover with normal
or nearly normal neurocognitive development.
Ohtahara syndrome, or early infantile epileptic
encephalopathy with burst-suppression (EIEE), is
a neonatal syndrome with frequent tonic seizures
and is associated with burstsuppression on the
interictal EEG.2830 This syndrome often evolves
into the West syndrome and subsequently into the
Lennox-Gastaut syndrome, and is most often associated with brain structural abnormalities including unilateral or bilateral cerebral hypoplasia and
other developmental malformations. The prognosis
for neurocognitive development is grim.
Infancy
Epilepsy of infancy with migrating focal

seizures is a rare, severe, and progressive focal
epilepsy in which focal seizures arise in multiple
bihemispheric regions and are refractory to medications.31,32 Brain magnetic resonance imaging
(MRI) studies initially are normal but show progressive atrophy. Many of these children die in the first
year, and most continue to have refractory seizures
throughout childhood, with severe developmental
delay and microcephaly.
West syndrome is an uncommon electroclinical syndrome of multiple etiologies characterized
by the triad of infantile spasms, hypsarrhythmia on
EEG, and developmental regression.3340 Tuberous
sclerosis is the single most common cause; other
causes include focal cortical dysplasias, other malformations of cortical development such as lissencephaly, perinatal asphyxia and infarction, prenatal
and postnatal brain infections, and various other cerebral structural lesions and metabolic syndromes.
A small number of these patients have no identifiable cause; this idiopathic West syndrome has a
more favorable prognosis for cessation of seizures
and normal development. Many West syndrome patients evolve into the Lennox-Gastaut syndrome and
other generalized epilepsies with mental retardation.
The spasms are difficult to treat with medications,
including adrenocorticotropic hormone (ACTH) and
vigabatrin, and multilobar resections have been
used when one hemisphere predominates in malformation or epileptiform activity, in some cases with
reportedly good functional outcomes.

Myoclonic epilepsy in infancy (MEI) is a rare
syndrome in which subtle or massive myoclonic
jerks occur in clusters of a few seconds duration
or somewhat longer.4143 The interictal EEG is normal, while during jerks there are generalized fast
spike-/polyspike-wave discharges. No other types
of seizures occur; the myoclonic seizures usually
are controlled with valproate, and most patients
with MEI have no seizures later in life.
Benign infantile epilepsy and benign familial
infantile epilepsy feature partial seizures with or
without secondary generalization that most often
begin between 6 months and 2 years of age.4448
The interictal EEG usually is normal, although
some have midline spikes during slow-wave sleep.
Ictal EEG recordings show clear focal onsets, most
often with either temporal or centroparietal maxima
across this population (but a single ictal onset
pattern in an individual patient). Brian imaging is
normal. Often patients have an associated viral
gastroenteritis, without encephalitis. Acute therapy
with antiseizure agents may be unnecessary. Seizure recurrence later in life is rare and normal intellectual development is expected.
Dravet syndrome is a rare and progressive
epileptic encephalopathy that usually begins with
febrile and afebrile generalized and unilateral clonic
or tonic-clonic seizures in infancy, when the EEG
is normal interictally.4953 Ongoing seizures and developmental delay are associated with findings of
generalized spike- and polyspike-wave and diffuse
theta slowing on the waking EEG by 2 years. This
syndrome can occur with GEFS+, but in these instances is rarely familial, as new mutations account
for most cases of GEFS+ with Dravet syndrome.
Myoclonic encephalopathy in nonprogressive disorders (also termed myoclonic status in
nonprogressive encephalopathy) is usually evident
by the end of the first year of life, manifesting as
developmental delays that will constitute severe

mental retardation and as refractory myoclonic absences.5457 Irregular and fragmented spike-wave
discharges and low-amplitude multifocal spikes
occur with generalized slowing of the waking EEG.
Most of these patients have a genetic developmental disorder, with Angelman syndrome predominating over the 4p-deletion syndrome (Wolf
Hirschhorn syndrome) and Rett syndrome, but
perinatal anoxia also can cause this electroclinical
syndrome.
Childhood
Childhood absence epilepsy (CAE) or pyknolepsy is the most widely recognized form of
epilepsy in childhood, but not the most common,
with a prevalence of less than 10% in children
with epilepsy.5867 Seizure onset is usually at 3 to 8
years of age in children with normal development.
Most have only absence (petit mal) seizures, often
occurring multiple times daily before treatment, but
some also rarely experience generalized tonicclonic (GTC) seizures. The interictal EEG is usually normal except for brief bursts of generalized
3-per-second spike-wave discharges, which are
provoked with photic stimulation and hyperventilation; often there is also occipital intermittent
rhythmic delta slowing. Generalized 3-per-second
spike-wave discharges usually last 10 to 20 seconds during the seizures. Brain imaging is generally considered unnecessary, as no lesional or
acquired epilepsies cause these types of seizures
with these EEG findings. Ethosuximide is usually
effective for absences, and valproate for both absences and GTC seizures. Seizures cease by the
teens in over 90% of patients, and those whose
seizures persist most often evolve into the juvenile
myoclonic epilepsy syndrome.
Lennox-Gastaut syndrome (LGS) begins at

age 3 to 8 years or rarely later, but in perhaps 20%
of cases is preceded by the West syndrome.68-73
This archetypal symptomatic or cryptogenic generalized epilepsy is defined by mixed seizure types,
generalized slow spike-wave discharges and generalized slowing on waking-drowsy interictal EEG,
generalized paroxysmal fast activity on sleeping
interictal EEG, and developmental delay. The typical seizure is a medically refractory drop attack as
a generalized tonic seizure. Atypical absences and
GTC seizures are very common. Generalized atonic, generalized clonic, generalized myoclonic, and
focal seizures often occur. Later age of onset and
relatively normal intellect sometimes are observed.
Etiologies include the phakomatoses, various malformations of cortical development, early diffuse
anoxic and focal ischemic injuries, and others as
for the West syndrome. Cryptogenic LGS with
normal brain MRI accounts for perhaps one-third
of cases. Valproate, zonisamide, and other agents
are typical of the polytherapy needed to avoid status epilepticus, but only infrequently is full seizure
control achieved in childhood. By adulthood, the
interictal EEG often evolves away from generalized slow spike-wave, so technically the individual
no longer has LGS, but often has the same types
of seizures under improved control. Focal seizures
occur in some patients with LGS, and the interictal
EEG may show more focal spike elements. Intellectual prognosis is poor, and psychosis, episodic
dyscontrol, and other disabling behavioral disorders are common.
Benign epilepsy with centrotemporal spikes
(BECTS) is the most common benign partial epilepsy of childhood, and the single most common
form of epilepsy in childhood.7483 Seizure onset
is usually at 3 to 13 years of age in children with
normal development. Most patients with BECTS
have nocturnal events that eventually are diag16 Hospital Physician Board Review Manual
nosed as focal seizures with sensory and motor

facial or glossopharyngeal seizures, often with
grunting or drooling. Diagnosis often occurs after
a first nocturnal GTC seizure. The interictal EEG
most often shows single and repetitive unilateral
or bilateral independent spike-wave complexes
of centrotemporal maximum, without focal delta
slowing at the spike site(s), but sometimes with
generalized 3-per-second spike-wave discharges.
Atypical clinical or EEG features may indicate the
need for brain imaging. When therapy is needed,
carbamazepine or other agents usually control the
seizures at modest doses. Epilepsy almost always
remits within several years of onset.
Benign epilepsy with occipital spikes (Panayiotopoulos syndrome) is the second most common benign partial epilepsy of childhood.8487
Focal seizure onset is usually at 3 to 6 years of
age in children with normal development, although
a large minority has a preceding history of febrile
convulsions. Most have focal seizures with gaze
deviation, emesis and other autonomic signs, and
impaired consciousness, with nocturnal predilection. Hemiconvulsions and GTC seizures are common. Interictal EEGs show normal background
activities with high-amplitude occipital spike-wave
complexes on eye closure, and spike activation
by sleep with unilateral or bisynchronous occipital
spikes; some also have other foci of spikes or generalized spike-wave bursts. Most have only a few
seizures, but paradoxically these few seizures frequently generate status epilepticus. Carbamazepine and valproate are usually effective, although
many do not require medication. Focal seizures
consistently cease within 2 years of onset.
Late onset childhood occipital epilepsy
(Gastaut type) is a rare condition that features focal
seizures beginning at age 6 to 12 years, with visual
hallucinations or blindness, often with gaze deviawww.turner-white.com

tion or eyelid fluttering, and often followed by postictal migraine headaches.8893 The focal seizures
often evolve into hemiconvulsions or GTC seizures.
The interictal EEG typically shows unilateral or bisynchronous occipital spikes of high amplitude with
fields extending over adjacent parietal and temporal
areas, and with attenuation on eye opening. Brain
MRI is normal. Seizures often are medially refractory, but tend to remit by the late teens.
Epilepsy with myoclonic atonic (astatic) seizures (Doose syndrome) is a rare syndrome with
onset at 2 to 5 years of age, usually in developmentally normal children.9497 The initial seizures
typically are repetitive GTC seizures, with only
isolated GTC seizures thereafter, but followed by
persisting epileptic drop attacks. The drop attacks
are generalized myoclonic-atonic (or myoclonic
astatic) seizures with components both of increased and decreased muscle tone. The interictal
EEG is abnormal due to generalized slowing in
waking with high-amplitude atypical generalized
spike-wave complexes at sleep onset. The ictal
EEG may be similar but with more and higher amplitude slowing and spiking, and often with greater
rhythmicity of slow waves and spikes. Brain MRI
is normal. Valproate can reduce seizures, which
usually remit after several months. Some of these
patients have persisting cognitive deficits.
Autosomal-dominant nocturnal frontal lobe
epilepsy (ADNFLE) is a rare syndrome with seizure onset in middle childhood and adolescence in
the majority of affected patients.98100 The disorder
was once considered to be paroxysmal nocturnal dystonia, but with the advent of video-EEG,
ictal recordings established the epileptic nature
of the events. These focal seizures have been
termed hypermotor because of their vigorous but
rather variable movements, which can be low- and
high-amplitude, synchronous or asynchronous or
alternating, and axial or appendicular. Untreated,

these seizures often occur repeatedly on many
nights. Most patients have no other type of seizure,
a normal interictal EEG, normal intelligence and
neurologic examination, and normal brain MRI.
Even the ictal EEG may be difficult to interpret,
often with anterior or diffuse attenuations or rhythmic slow waves rather than sharply construed or
high-amplitude focal discharges. Known causative
mutations code for subunits of neuronal nicotinic
receptors. Most patients with ADNFLE attain seizure control with carbamazepine or other agents,
but a sizeable minority do not attain seizure control
and may have increased risk of chronic neurobehavioral sequelae.
Epilepsy with myoclonic absences is a rare,
idiopathic generalized epilepsy with onset at age
1 to 12 years of myoclonic absences as the sole
seizure type, or as myoclonic absences with other
seizure, particularly GTCs.101103 Myoclonic absences briefly impair awareness, with proximal arm and
other jerks during transitory increases in tone that
cause the arms to elevate for a few seconds, rarely
with falling. The interictal and ictal EEG shows
Prognosis for medication control and later remission is generally good.
Epileptic encephalopathy with continuous
spike-and-waveduring sleep (CSWS), also
known as electrical status epilepticus in sleep
(ESES), is a rare cryptogenic syndrome in which
various focal or generalized (including absence)
seizures can occur in early-middle childhood.104,105
The requisite EEG feature is occurrence of generalized spike-wave discharge during greater than
85% of the non-REM sleep recording. Global cognitive decline occurs and usually leaves permanent
deficits, despite relative ease of medication control
of seizures and later remission of epilepsy.

Landau-Kleffner syndrome (LKS) is a rare
cryptogenic syndrome that is highly associated
with CSWS, as the same non-REM spike-wave
discharges occur, with similar types of seizures
and medication responsiveness as in CSWS.106,107
A progressive loss of previously acquired language
function defines LKS, and after epilepsy remits permanent auditory agnosia and aphasia are common.
Febrile seizures plus (FS+) (more often termed
generalized, or genetic, epilepsy with febrile seizures plus, or GEFS+) is an electroclinical-genetic
syndrome with a starting point of febrile convulsions of early childhood or infancy, but a wide
range of subsequent epilepsy manifestations that
have considerable overlap with other electroclinical
syndromes.108,109 These syndromes include myoclonic-astatic epilepsy, Dravet syndrome, various
generalized epilepsies, and familial temporal lobe
epilepsy TLE with or without hippocampal sclerosis. Some affected individuals have only febrile
seizures. Early publications reported genes whose
products disrupted neuronal sodium channel function at the ionophores alpha subunit (SCN1A mutations), but other sodium channel components,
and in some cases GABAA receptor subunits,
are affected by more recently reported genes that
cause GEFS+.
AdolescenceAdult
Juvenile absence epilepsy (JAE) is somewhat

more common that CAE.5867 Many authorities
consider CAE and JAE to be a continuum. Seizure
onset is usually at 8 to 12 years of age in children
with normal development. In addition to absence
seizures, which tend to occur less frequently
before treatment in JAE than in CAE, most also
occasionally experience GTC seizures. Interictal
and ictal EEGs in JAE are highly similar to those
of CAE. Valproate may be most effective for both
absence and GTC seizures, but concerns with

teratogenicity in young women often favor use of
lamotrigine or other agents. Seizures cease in the
late teens in over 80% of patients, with more than
10 lifetime GTC seizures being a negative prognostic sign. As with CAE, most nonremitters evolve
into JME.
Juvenile myoclonic epilepsy (JME) probably
is the second most common epileptic syndrome
across all ages, after mesial TLE, and accounts
for perhaps one-sixth of adult epilepsies.110114
Seizure onset is usually at ages 12 to 18 years
in individuals with normal development, and may
follow on CAE or JAE. Myoclonus in early waking
states is positive or negative, and segmental or
massive; massive negative myoclonus can cause
an injurious fall without loss of consciousness.
Occurrence of at least 1 GTC seizure has been
a formal requirement for this diagnosis, but GTC
seizures should be rare after medication initiation
with good compliance and avoidance of the principal precipitants (sleep deprivation and ethanol).
Approximately one-third of those with JME have
absence seizures. The interictal EEG typically is
normal except for brief, generalized, fast (46-persecond) spike-/polyspike-wave discharges, often
increased with photic stimulation and hyperventilation, or sometimes with generalized 3-per-second
spike-wave discharges. Jerks often coincide with
polyspikes, but ictal recordings are rarely if ever
needed for diagnosis. Valproate (in those without
child-bearing potential), zonisamide, lamotrigine,
and other agents usually can control seizures fully
in patients with good medication and lifestyle compliance. Unlike other idiopathic generalized epilepsies, prognosis for remission is very poor, with
reports of GTC seizure recurrence in elderly JME
patients on medication withdrawal after decades of
seizure freedom.

Epilepsy with generalized tonic-clonic seizures alone is clearly a common situation. As
an epileptic syndrome, it suffers from a paucity
of published research, with no defined age-range
of onset and no established diagnostic criteria to
fully distinguish the syndrome from recurrent GTC
seizures of other causes.115,116 Seizure frequency
and relationship to seizure-provoking factors is
poorly defined. Interictal EEG sometimes shows
Brain MRI presumably is normal in this idiopathic
epilepsy. Medications are chosen for seizure type
rather than epilepsy type, and prognosis for remission is unclear.
Progressive myoclonus epilepsies (PME) are
a well-defined set of etiologies with a common clinical syndrome, which unfortunately is most often
untreatable and progressive to early death.117121
The syndrome consists of myoclonus, mixed GTC
and other seizures, dementia, and usually other
progressive neurologic deficits, including ataxia.
Onset is usually in late childhood or adolescence,
depending on the etiology. The interictal EEG
shows generalized and multifocal slowing, multifocal spikes often with posterior predominance,
and atypical generalized spike-/polyspike-wave
discharges. Depending on the age of degeneration, cerebral atrophy is present on MRI. Causes
include Lafora disease, neuronal ceroid lipofuscinosis, myoclonus epilepsy and ragged red fibers
(MERRF), sialidosis, and other neurodegenerative
storage diseases, each with specific biochemical or tissue studies allowing diagnosis. Seizures
are refractory and decline is inexorable, except in
Baltic familial myoclonus epilepsy (Unverricht-Lundborg disease), an autosomal recessive condition
that probably occurs in most human populations,
although somewhat less rarely near the Baltic Sea.
Most cases involve mutations in genes encoding
cystatin B, a cysteine protease inhibitor, with some

mutations developed for clinical tests. Baltic familial
myoclonus epilepsy features cognitive decline that
can be stabilized if seizures are controlled, which
also prolongs survival. Valproate and zonisamide
are the medications most frequently used for seizure control in PME.
Autosomal dominant epilepsy with auditory features (ADEAF) is a rare TLE of teenage
or early adult onset, characterized by auras with
unformed auditory hallucinations and frequent
GTC seizures.122,123 The interictal EEG is normal or
shows interictal spikes of posterior temporal maximum. Brain MRI is normal or may show subtle enlargement of lateral temporal cortex without clearly
dysplastic features. Seizures generally are easily
controlled with medications.
Other familial TLEs are uncommon, and are
often associated with febrile convulsions before
onset of auras, focal seizures with impaired awareness, and GTC seizures similar to those of mesial
TLE with hippocampal sclerosis.124127 Interictal and
ictal EEGs are similar to those of mesial TLE with
hippocampal sclerosis, and some individuals have
hippocampal atrophy on MRI. Clear distinction of
familial from sporadic mesial TLE probably will
require genetic tests that are yet to be developed.
Less specific age relationship
Familial focal epilepsy with variable foci is

a rare syndrome with variable onset in childhood
or adulthood. In this syndrome, each affected individual has focal epilepsy limited to one invariant
focus, but the family has individuals with different
foci in frontal, temporal, and occipital lobes.127,128
Focal seizures are defined by semiology and EEG
abnormalities, as brain MRI is consistently normal.
Reflex epilepsies must be differentiated from
reflex seizures.129131 Many forms of epilepsy feature

generalized or focal seizures that sometimes occur
immediately on photic stimulation, startle, or other
particular stimuli, but these seizures also occur
spontaneously in the absence of the potentially
ictogenic stimulus. In reflex epilepsy, the seizures
should occur only in response to a specific set of
stimuli. The prototypical example of reflex epilepsy
is primary reading epilepsy. In this very rare and
quite remarkable syndrome, the patient can predictably induce focal seizures by reading complex
material for prolonged periods of time, after which
mandibular myoclonus or orofacial sensations or
movements occur. If the individual persists in reading, a GTC seizure consistently ensues. Interictal
EEG and brain MRI are normal, but bilateral or
unilateral EEG spikes of left temporoparietal predominance occur during the focal seizures.
Distinctive constellations and less
specific age relationship
Mesial temporal lobe epilepsy with hippocampalsclerosis (MTLE-HS) is probably the

single most common form of epilepsy, if one allows for limitations in detection of very mild hippocampal sclerosis by current clinical MRI techniques.125,132139 Habitual seizure types often are
preceded by febrile convulsions. The typical auras,
focal seizures with impaired awareness and with
or without automatisms, and afebrile GTC seizures
can begin by 2 or 3 years of age, but more often
begin in middle childhood or well into adulthood.
Psychic and autonomic auras can include dreamy
states with perceived unreality or dj vu or jamais
vu phenomena, gustatory or olfactory hallucinations, epigastric rising sensations, and a variety
of other symptoms. With more widespread ictal
discharges, an initial motionless staring spell often
is followed by chewing, swallowing, nonspecific
hand movements, and various other automatisms.
Evolution into a GTC seizure may be immediately preceded by oculocephalic version. Typical
interictal EEG findings include unilateral or bilateral anterior temporal spikes or runs of intermittent
rhythmic delta activity (specific TLE discharges),
nonspecific focal temporal or generalized slowing, or a persistently normal interictal EEG. Typical
ictal discharges are focal frontotemporal rhythmic
discharges that can be sinusoidal or sharply contoured and evolve in field, frequency, and morphology, or similar discharges that are nonlocalizing
at onset and sometimes develop later temporal
maximum. Brian MRI can be normal or nonspecifically abnormal (with subcortical white matter signal
alterations, for example), but the classic signs are
unilateral or rarely bilateral hippocampal atrophy
and T2 signal increase. This syndrome is medically refractory in perhaps 50% of individuals, but
is more likely to be amenable to surgical resection
than are most other epilepsies.
Rasmussen syndrome is an electroclinical syndrome of epilepsia partialis continua with progressive atrophy of the affected cerebral hemisphere
and profound medication refractoriness.140144 Characteristic onset is in early to middle childhood,
but considerably later onset is recognized, as are
variants with aphasic or other focal seizures rather
than focal motor seizures. The clinical and EEG abnormalities are highly lateralized, with EEG slowing,
spikes and seizures continuing over months and
years, usually with limited response to tolerable or
intoxicating polypharmacy. Serial brain MRI shows
progressive atrophy of the affected hemisphere,
correlating with progressive hemiparesis. Brian tissue shows characteristic microglial proliferation
and nodularization, perivascular lymphocytic cuffing, and neuronal loss and gliosis in the affected
hemisphere. T-cell dysfunction and other lines of
evidence support various anti-inflammatory and

immune-modulating therapies, which possibly blunt
the severity of cerebral degeneration over the years
of ongoing seizures. Functional hemispherectomy
may allow the other hemisphere to develop more
normally, with seizure control, in selected children.
Gelastic seizures with hypothalamic hamartoma is a rare syndrome of focal seizures with
mirthless laughter and GTC seizures that is specifically associated with a neuronal-glial hamartoma of
the hypothalamus.145147 Precocious puberty, ictal
semiology, and brain MRI findings are diagnostic.
Interictal and ictal EEG epileptiform findings are variable. Seizures often are intractable, but resective or
radiosurgical procedures have significant efficacy.
Hemiconvulsion-hemiplegia-epilepsy (HHE)
is a rare syndrome most often of early childhood
onset.148150 The first manifestation usually is hemiconvulsive status epilepticus lasting one to several
hours, or longer if untreated. After status ends, a
new postictal hemiplegia persists. After a latent
period of 1 to 4 years, focal seizures begin to
occur as complex partial seizures (focal seizures
with impaired awareness), focal clonic seizures, or
other types of focal seizures. These seizures may
be controlled with medications, or sometimes with
resective surgery. The optimal therapy is aggressive management of all childhood status epilepticus, and with improving health care delivery the
incidence of HHE appears to have declined.
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References
1. Hesdorffer DC, Logroscino G, Benn EK, et al. Estimating
risk for developing epilepsy: a population-based study in
Rochester, Minnesota. Neurology. 2011;76:237.
2. Henry TR, Roman DD. Presurgical epilepsy localiztion with interictal cerebral dysfunction. Epilepsy Behav
2011;20:194208.
3. Fisher RS, Boas WVE, 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 2005;46:4702.
4. Beghi E, Carpio A, Forsgren L, et al. Recommendation
for a definition of acute symptomatic seizure. Epilepsia
2010;51:6715.
5. Matsumoto H, Ajmone Marsan C. Cellular mechanisms in
experimental epileptic seizures. Science 1964;144:1934.
6. Holmes GL, Ben-Ari Y. Seizing hold of seizures. Nature
Med 2003;9:9946.
7. Bragin A, Engel J Jr, Wilson CL, et al. Hippocampal and
entorhinal cortex high-frequency oscillations (100--500 Hz)
in human epileptic brain and in kainic acid--treated rats
with chronic seizures. Epilepsia 1999;40:12737.
8. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med
2003;349:125766.
9. Fisher RS. Animal models of the epilepsies. Brain Res
Brain Res Rev 1989;14:24578.
10. Proposal for revised clinical and electrographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League
Against Epilepsy. Epilepsia 1981;22:489501.
11. Syed TU, LaFrance EC, Kahriman ES, et al. Can semiology predict psychogenic nonepileptic seizures? a prospective study. Ann Neurol 2011;69:9971004.
12. Derry CP, Duncan JS, Berkovic SF. Paroxysmal motor disorders of sleep: The clinical spectrum and differentiation
from epilepsy. Epilepsia 2006;47:177591.
13. Parry SW, Tan MP. An approach to the evaluation and
management of syncope in adults. BMJ 2010;340:c880.
14. Devinsky O, Gazzola D, LaFrance WC. Differentiating
between nonepileptic and epileptic seizures. Nature Rev
Neurosci 2011;7:21020.
15. Henry TR, Drury I. Non-epileptic seizures in temporal
lobectomy candidates with medically refractory seizures.
Neurology 1997;48:137482.
16. Pillai J, Sperling MR. Interictal EEG and the diagnosis of
epilepsy. Epilepsia 2006;47(suppl 1):1422.
17. Gilliam F, Kuzniecky R, Faught E. Ambulatory EEG monitoring. J Clin Neurophysiol 1999;16:111115.
18. Cascino GD. Video-EEG monitoring in adults. Epilepsia
2002;43(suppl 3):8093.
19. Proposal for revised classification of epilepsies and epileptic syndromes. From the Commission on Classification and
Terminology of the International League Against Epilepsy.
Epilepsia 1989;30:38999.
20. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminol-

ogy and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and
Terminology, 2005-2009. Epilepsia 2010;51:67685.
21. Berkovic SF, Heron SE, Giordano L, et al. Benign familial
neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol 2004;55:5507.
22. Hirsch E, Velez A, Sellal F, et al. Electroclinical signs
of benign neonatal familial convulsions. Ann Neurol
1993;34:83541.
23. Leppert M, Anderson VE, Quattlebaum T, et al. Benign
familial neonatal convulsions linked to genetic markers on
chromosome 20. Nature 1989;337:6478.
24. Shevell MI, Sinclair DB, Metrakos K. Benign familial neonatal seizures: clinical and electroencephalographic characteristics. Pediatr Neurol 1986;2:2725.
25. Dalla Bernardina B, Zullini E, Fontana E. Electroclinical
longitudinal study of ten cases of Angelmans syndrome.
Epilepsia 1993;34(Suppl 2):71.
26. Lombroso CT. Early myoclonic encephalopathy, early infantile epileptic encephalopathy, and benign and severe infantile myoclonic epilepsies: a critical review and personal
contributions. J Clin Neurophysiol 1990;7:380408.
27. Ohtahara S, Yamatogi Y. Epileptic encephalopathies in
early infancy with suppression-burst. J Clin Neurophysiol
2003;20:398407.
28. Fusco L, Pachatz C, Di Capua M, Vigevano F. Video/
EEG aspects of early-infantile epileptic encephalopathy
with suppression-bursts (Ohtahara syndrome). Brain Dev
2001;23:70814.
29. Mizrahi EM, Clancy RR. Neonatal seizures: early-onset
seizure syndromes and their consequences for development. Ment Retard Dev Disabil Res Rev 2000;6:22941.
30. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E. The earlyinfantile epileptic encephalopathy with suppression-burst:
developmental aspects. Brain Dev 1987;9:3716.
31. Coppola G, Plouin P, Chiron C, et al. Migrating partial seizures in infancy: a malignant disorder with developmental
arrest. Epilepsia 1995;36:101724.
32. Wilmshurst JM, Appleton DB, Grattan-Smith PJ. Migrating
partial seizures in infancy: two new cases. J Child Neurol
2000;15:71722.
33. Alvarez LA, Shinnar S, and Moshe SL. Infantile spasms due
to unilateral cerebral infarcts. Pediatrics 1987;79:10246.
34. Asano E, Juhasz C, Shah A, et al. Origin and propagation
of epileptic spasms delineated on electrocorticography.
Epilepsia 2005;46:108697.
35. Bachman DS. Spontaneous remission of infantile spasms
with hypsarrhythmia. Arch Neurol 1981;38: 785.
36. Chiron C, Dumas C, Jambaque I, et al. Randomized
trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res
1997;26:38995.
37. Chugani HT, Shields WD, Shewmon DA, et al. Infantile
spasms: I. PET identifies focal cortical dysgenesis in
cryptogenic cases for surgical treatment. Ann Neurol
1990;27:40613.
38. Dulac O, Plouin P, Jambaque I. Predicting favorable outcome in idiopathic West syndrome. Epilepsia 1993;34:747
56.
39. Kuzniecky R, Andermann F, Guerrini R. Infantile spasms:
an early epileptic manifestation in some patients with the
congenital bilateral perisylvian syndrome. J Child Neurol
1994;9:4203.
40. Lombroso CT. A prospective study of infantile spasms: clinical and therapeutic correlations. Epilepsia 1983;24:135
58.
41. Auvin S, Pandit F, De Bellecize J, et al. Benign myoclonic
epilepsy in infants: electroclinical features and long-term
follow-up of 34 patients. Epilepsia 2006;47:38793.
42. Darra F, Fiorini E, Zoccante L, et al Benign myoclonic epilepsy in infancy (BMEI): a longitudinal electroclinical study
of 22 cases. Epilepsia 2006;47 Suppl 5:3135.
43. Lombroso CT, Fejerman N. Benign myoclonus of early
infancy. Ann Neurol 1977;1:13843.
44. Capovilla G, Beccaria F. Benign partial epilepsy in infancy
and early childhood with vertex spikes and waves during
sleep: a new epileptic form. Brain Dev 2000;22:9398.
45. Dulac O, Cusmai R, de Oliveira K. Is there a partial benign
epilepsy in infancy? Epilepsia 1989;30:798801.
46. Nelson GB, Olson DM, Hahn JS. Short duration of benign
partial epilepsy in infancy. J Child Neurol 2002;17:4405.
47. Okumura A, Watanabe K, Negoro T, et al. Long-term
follow-up of patients with benign partial epilepsy in infancy.
Epilepsia 2006;47:1815.
48. Watanabe K, Yamamoto N, Negoro T, et al. Benign complex
partial epilepsies in infancy. Pediatr Neurol 1987;3:20811.
49. Dravet C, Bureau M, Oguni H, et al. Severe myoclonic epilepsy in infancy (Dravet syndrome). In: Roger J, Bureau M,
Dravet C, et al, eds. Epileptic syndromes in infancy, childhood and adolescence. 4th ed. London: John Libbey: 2005.
50. Fukuma G, Oguni H, Shirasaka Y, et al. Mutations of
neuronal voltage-gated Na+ channel alpha 1 subunit
gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB). Epilepsia
2004;45:1408.
51. Siegler Z, Barsi P, Neuwirth M, et al. Hippocampal sclerosis in severe myoclonic epilepsy in infancy: a retrospective
MRI study. Epilepsia 2005;46:7048.
52. Singh R, Andermann E, Whitehouse WP, et al. Severe
myoclonic epilepsy of infancy: extended spectrum of
GEFS+? Epilepsia 2001;42:83744.
53. Yakoub M, Dulac O, Jambaque I, et al. Early diagno-

sis of severe myoclonic epilepsy in infancy. Brain Dev
1992;14:299303.
54. Aicardi J, Chevrie JJ. Myoclonic epilepsies of childhood.
Neuropadiatrie 1971;3:17790.
55. Dalla Bernardina B, Dulac O, Fejerman N, et al. Early myoclonic epileptic encephalopathy (E.M.E.E.). Eur J Pediatr
1983;140:24852.
56. Erba G, Lombroso CT. Angelmans (Happy Puppet) syndrome: Clinical, CT scan and serial electroencephalographic study. Clin Electroencephalogr 1973;20: 12840.
57. Dalla Bernardina B, Fontana E, Darra F. Myoclonic
status in nonprogressive encephalopathies. Adv Neurol
2005;95:5970.
58. Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform
EEG activity. Brain 1984;107( Pt 1):293308.
59. Berkovic SF, Andermann F, Andermann E, Gloor P. Concepts of absence epilepsies: discrete syndromes or biological continuum? Neurology 1987;37:9931000.
60. Browne TR, Dreifuss FE, Penry JK, et al. Clinical and
EEG estimates of absence seizure frequency. Arch Neurol
1983;40:46972.
61. Cobb WA, Gordon N, Matthews SC, et al. The occipital
delta rhythm in petit mal. Electroencephalogr Clin Neurophysiol 1961;13:1423.
62. Holmes GL, McKeever M, Adamson M. Absence seizures
in children: clinical and electroencephalographic features.
Ann Neurol 1987;21:26873.
63. Lennox WG. The petit mal epilepsies; their treatment with
tridione. J Am Med Assoc 1945;129:106974.
64. Meencke HJ, Janz D. Neuropathological findings in primary generalized epilepsy: a study of eight cases. Epilepsia
1984;25:821.
65. Penry JK, Porter RJ, Dreifuss RE. Simultaneous recording
of absence seizures with video tape and electroencephalography. A study of 374 seizures in 48 patients. Brain
1975;98:42740.
66. Wirrell EC, Camfield CS, Camfield PR, et al. Long-term
prognosis of typical childhood absence epilepsy: remission
or progression to juvenile myoclonic epilepsy. Neurology
1996;47:91218.
67. Wolf P, Goosses R. Relation of photosensitivity to epileptic
syndromes. J Neurol Neurosurg Psychiatry 1986;49:1386
91.
68. Bauer G, Aichner F, Saltuari L. Epilepsies with diffuse slow
spikes and waves of late onset. Eur Neurol 1983;22:344
50.
69. Chugani HT, Mazziotta JC, Engel J Jr. Phelps ME. The
Lennox-Gastaut syndrome: metabolic subtypes determined by 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography. Ann Neurol 1987;21: 413.
70. Gastraut H, Roger J, Soulayrol R, et al. Childhood epileptic

encephalopathy with diffuse slow spike-waves (otherwise
known as petit mal variant) or Lennox syndrome. Epilepsia 1966;7:13979.
71. Lennox WG, Davis JP. Clinical correlates of the fast and
the slow spike-wave electroencephalogram. Pediatrics
1950;5:62644.
72. Ohtahara S, Yamatogi Y, Ohtsuka Y. Prognosis of the Lennox syndrome-long-term clinical and electroencephalographic follow-up study, especially with special reference
to relationship with the West syndrome. Folia Psychiatr
Neurol Jpn 1976;30:27587.
73. Tassinari CA, Dravet C, Roger J, et al. Tonic status
epilepticus precipitated by intravenous benzodiazepine
in five patients with Lennox-Gastaut syndrome. Epilepsia
1972;13:42135.
74. Aicardi J, Chevrie JJ. Atypical benign partial epilepsy of
childhood. Dev Med Child Neurol 1982;24:28192.
75. Beydoun A, Garofalo EA, Drury I. Generalized spikewaves, multiple loci, and clinical course in children with
EEG features of benign epilepsy of childhood with centrotemporal spikes. Epilepsia 1992;33:10916.
76. Blom S, Heijbel J. Benign epilepsy of children with centrotemporal EEG foci: a follow-up study in adulthood of patients initially studied as children. Epilepsia 1982;23:629
32.
77. Caraballo R, Cersosimo R, Fejerman N. Idiopathic partial
epilepsies with rolandic and occipital spikes appearing in
the same children. J Epilepsy 1998;11:26164.
78. Bernardina BD, Beghini G. Rolandic spikes in children with
and without epilepsy. (20 subjects polygraphically studied
during sleep). Epilepsia 1976;17:1617.
79. Gelisse P, Corda D, Raybaud C, et al. Abnormal neuroimaging in patients with benign epilepsy with centrotemporal
spikes. Epilepsia 2003;44:3728.
80. Kramer U, Zelnik N, Lerman-Sagie T, Shahar E. Benign
childhood epilepsy with centrotemporal spikes: clinical
characteristics and identification of patients at risk for multiple seizures. J Child Neurol 2002;17:1719.
81. Lerman P, Kivity S. Benign focal epilepsy of childhood. A
follow-up study of 100 recovered patients. Arch Neurol
1975;32:2614.
82. Lombroso CT. Sylvian seizures and midtemporal spike foci
in children. Arch Neurol 1967;17:5259.
83. Wirrell EC, Camfield PR, Gordon KE, et al. Benign rolandic
epilepsy: atypical features are very common. J Child Neurol 1995;10:4558.
84. Caraballo RH, Sologuestua A, Granana N, et al. Idiopathic
occipital and absence epilepsies appearing in the same
children. Pediatr Neurol 2004;30:2428.
85. Kuzniecky R, Rosenblatt B. Benign occipital epilepsy: a

family study. Epilepsia 1987;28:34650.
86. Panayiotopoulos CP. Benign childhood epilepsy with occipital paroxysms: a 15-year prospective study. Ann Neurol
1989;26:5156.
87. Panayiotopoulos CP. Elementary visual hallucinations,
blindness, and headache in idiopathic occipital epilepsy:
differentiation from migraine. J Neurol Neurosurg Psychiatry 1999;66:53640.
88. Blume WT, Wiebe S, Tapsell LM. Occipital epilepsy: lateral
versus mesial. Brain 2005;128:120925.
89. Fejerman N. [Atypical evolution of benign partial epilepsy
in children]. Rev Neurol 1996;24:141520.
90. Gastaut H. A new type of epilepsy: benign partial epilepsy
of childhood with occipital spike-waves. Clin Electroencephalogr 1982;13:1322.
91. Kivity S, Ephraim T, Weitz R, Tamir A. Childhood epilepsy
with occipital paroxysms: clinical variants in 134 patients.
Epilepsia 2000;41:152233.
92. Ludwig BI, Marsan CA. Clinical ictal patterns in epileptic
patients with occipital electroencephalographic foci. Neurology 1975;25:46371.
93. Talwar D, Rask CA, Torres F. Clinical manifestations in
children with occipital spike-wave paroxysms. Epilepsia
1992;33:66774.
94. Doose H. Myoclonic astatic epilepsy of early childhood.
In: Roger J, Bureau M, Dravet C, et al, eds. Epileptic syndromes in infancy, childhood and adolescence. London:
John Libbey: 2005.
95. Dulac O, Plouin P, Shewmon A. Myoclonus and epilepsy
in childhood: 1996 Royaumont meeting. Epilepsy Res
1998;30:91106.
96. Nabbout R, Kozlovski A, Gennaro E, et al. Absence of
mutations in major GEFS+ genes in myoclonic astatic epilepsy. Epilepsy Res 2003;56:12733.
97. Oguni H, Fukuyama Y, Imaizumi Y, Uehara T. VideoEEG analysis of drop seizures in myoclonic astatic
epilepsy of early childhood (Doose syndrome). Epilepsia
1992;33:80513.
98. Hirsch E, Sellal F, Maton B, et al. Nocturnal paroxysmal
dystonia: a clinical form of focal epilepsy. Neurophysiol Clin
1994;24:20717.
99. Meierkord H, Fish DR, Smith SJ, et al. Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy? Mov Disord
1992;7:3842.
100. Scheffer IE, Bhatia KP, Lopes-Cendes I, et al. Autosomal
dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain 1995;118 ( Pt 1):6173.
101. Capovilla G, Rubboli G, Beccaria F, et al. A clinical spectrum of the myoclonic manifestations associated with
typical absences in childhood absence epilepsy. A videopolygraphic study. Epileptic Disord 2001;3:5762.
102. Guerrini R, Bureau M, Mattei MG, et al. Trisomy 12p

syndrome: a chromosomal disorder associated with
generalized 3-Hz spike and wave discharges. Epilepsia
1990;31:55766.
103. Manonmani V, Wallace SJ. Epilepsy with myoclonic absences. Arch Dis Child 1994;70:28890.
104. Patry G, Lyagoubi S, Tassinari CA. Subclinical electrical
status epilepticus induced by sleep in children. A clinical
and electroencephalographic study of six cases. Arch Neurol 1971;24:24252.
105. Praline J, Hommet C, Barthez MA, et al. Outcome at adulthood of the continuous spike-waves during slow sleep and
Landau-Kleffner syndromes. Epilepsia 2003;44:143440.
106. Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner
syndrome: a clinical and EEG study of five cases. Epilepsia
1990;31:75667.
107. Landau WM, Kleffner FR. Syndrome of acquired aphasia
with convulsive disorder in children. Neurology 1957;7:523
30.
108. Escayg A, Heils A, MacDonald BT, et al. A novel SCN1A
mutation associated with generalized epilepsy with febrile
seizures plus--and prevalence of variants in patients with
epilepsy. Am J Hum Genet 2001;68:86673.
109. Scheffer IE, Berkovic SF. Generalized epilepsy with febrile
seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain 1997;120 (Pt 3):47990.
110. Aliberti V, Grunewald RA, Panayiotopoulos CP, Chroni E.
Focal electroencephalographic abnormalities in juvenile
myoclonic epilepsy. Epilepsia 1994;35:297301.
111. Asconape J, Penry JK. Some clinical and EEG aspects of benign juvenile myoclonic epilepsy. Epilepsia
1984;25:10814.
112. Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic
epilepsy of Janz. Neurology 1984;34:28594.
113. Janz D, Christian W. Impulsiv-Petit mal. Dtsch Z Nervenheilkd 1957;176:34886.
114. Zifkin B, Andermann E, Andermann F. Mechanisms, genetics, and pathogenesis of juvenile myoclonic epilepsy.
Curr Opin Neurol 2005;18:14753.
115. Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 1991;41:96572.
116. Hauser WA, Anderson VE, Loewenson RB, McRoberts
SM. Seizure recurrence after a first unprovoked seizure. N
Engl J Med 1982;307:5228.
117. Berkovic SF, Andermann F, Carpenter S, Wolfe LS. Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med 1986;315:296305.
118. Koskiniemi M, Toivakka E, Donner M. Progressive myoclonus epilepsy. Electroencephalographical findings. Acta
Neurol Scand 1974;50:33359.

119. Lafreniere RG, Rochefort DL, Chretien N, et al. Unstable
insertion in the 5 flanking region of the cystatin B gene
is the most common mutation in progressive myoclonus
epilepsy type 1, EPM1. Nat Genet 1997;15:298302.
120. Magaudda A, Ferlazzo E, Nguyen VH, Genton P. Unverricht-Lundborg disease, a condition with self-limited
progression: long-term follow-up of 20 patients. Epilepsia
2006;47:8606.
121. Shibasaki H, Yamashita Y, Neshige R, et al. Pathogenesis
of giant somatosensory evoked potentials in progressive
myoclonic epilepsy. Brain 1985;108(Pt 1):22540.
122. Michelucci R, Poza JJ, Sofia V, et al. Autosomal dominant
lateral temporal epilepsy: clinical spectrum, new epitempin
mutations, and genetic heterogeneity in seven European
families. Epilepsia 2003;44:128997.
123. Winawer MR, Martinelli Boneschi F, Barker-Cummings C,
et al. Four new families with autosomal dominant partial
epilepsy with auditory features: clinical description and
linkage to chromosome 10q24. Epilepsia 2002;43:6067.
124. Andermann E, Abou-Khalil B, Berkovic SF, et al. Deja-vu
is the characteristic aura in benign familial temporal lobe
epilepsy. Epilepsia 1997;38:200.
125. Cendes F, Lopes-Cendes I, Andermann E, Andermann F.
Familial temporal lobe epilepsy: a clinically heterogeneous
syndrome. Neurology 1998;50:5547.
126. Kobayashi E, Lopes-Cendes I, Guerreiro CA, et al. Seizure
outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy. Neurology 2001;56:16672.
127. Scheffer IE, Phillips HA, OBrien CE, et al. Familial partial
epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. Ann
Neurol 1998;44:8909.
128. Berkovic SF, Serratosa JM, Phillips HA, et al. Familial partial epilepsy with variable foci: clinical features and linkage
to chromosome 22q12. Epilepsia 2004;45:105460.
129. Bickford RG, Whelan JL, Klass DW, Corbin KB. Reading
epilepsy: clinical and electroencephalographic studies of a
new syndrome. Trans Am Neurol Assoc 1956(81st meeting);100102.
130. Koutroumanidis M, Koepp MJ, Richardson MP, et al. The
variants of reading epilepsy. A clinical and video-EEG
study of 17 patients with reading-induced seizures. Brain
1998;121(Pt 8):140927.
131. Matthews WB, Wright FK. Hereditary primary reading epilepsy. Neurology 1967;17:91921.
132. Cascino GD, Jack CR, Jr, Parisi JE, et al. Magnetic resonance imaging-based volume studies in temporal lobe epilepsy: pathological correlations. Ann Neurol 1991;30:31
36.
133. Engel JJ. Current concepts: surgery for seizures. N Engl J
Med 1996;334:64752.
134. Engel J Jr, Wiebe S, French J, et al. Practice parameter:

temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the
American Academy of Neurology, in association with the
American Epilepsy Society and the American Association
of Neurological Surgeons. Neurology 2003;60:53847.
135. French JA, Williamson PD, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: I. Results of history
and physical examination. Ann Neurol 1993;34:77480.
136. Risinger MW, Engel J Jr, Van Ness PC, Henry TR, Crandall PH. Ictal localization of temporal lobe seizures with
scalp/sphenoidal recordings. Neurology 1989;39:128893.
137. So N, Gloor P, Quesney LF, et al. Depth electrode investigations in patients with bitemporal epileptiform abnormalities. Ann Neurol 1989;25:42331.
138. Sperling MR, OConnor MJ. Auras and subclinical seizures: characteristics and prognostic significance. Ann
Neurol 1990;28:3208.
139. Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal
scalp electroencephalography, neuropsychological testing,
neuroimaging, surgical results, and pathology. Ann Neurol
1993;34:7817.
140. Bien CG, Urbach H, Deckert M, et al. Diagnosis and staging of Rasmussens encephalitis by serial MRI and histopathology. Neurology 2002;58:2507.
141. Li Y, Uccelli A, Laxer KD, et al. Local-clonal expansion of
infiltrating T lymphocytes in chronic encephalitis of Rasmussen. J Immunol 1997;158:142837.
142. McLachlan RS, Girvin JP, Blume WT, Reichman H. Rasmussens chronic encephalitis in adults. Arch Neurol
1993;50:26974.
143. Rasmussen T, Olszewski J, Lloydsmith D. Focal seizures due to chronic localized encephalitis. Neurology
1958;8:43545.
144. Pardo CA, Vining EP, Guo L, et al. The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia
2003;45:51626.
145. Breningstall GN. Gelastic seizures, precocious puberty,
and hypothalamic hamartoma. Neurology 1985;35:1180
3.
146. Kahane P, Ryvlin P, Hoffmann D, et al. From hypothalamic
hamartoma to cortex: what can be learnt from depth recordings and stimulation? Epileptic Disord 2003;5:20517.
147. Kuzniecky R, Guthrie B, Mountz J, et al. Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy.
Ann Neurol 1997;42:6067.
148. Chauvel P, Dravet C. The HHE syndrome. In: Roger J, Bureau M, Dravet C, et al, eds. Epileptic syndromes in infancy,
childhood, and adolescence. London: John Libbey: 2005.

149. Freeman JL, Coleman LT, Smith LJ, Shield LK. Hemiconvulsion-hemiplegia-epilepsy syndrome: characteristic
early magnetic resonance imaging findings. J Child Neurol
2002;17:1016.
150. Roger J, Dravet C, Bureau M. Unilateral seizures: hemiconvulsions-hemiplegia syndrome (HH) and hemiconvulsionshemiplegia-epilepsy syndrome (HHE). Electroencephalogr
Clin Neurophysiol Suppl 1982;21121.
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Epilepsy Principles and Diagnosis

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Epilepsy Board Review Manual

Seizures and Epilepsy:

Professor of Neurology, Director, Comprehensive Epilepsy

PRESIDENT, Group PUBLISHER

NOTE FROM THE PUBLISHER:

Board Review Questions. . . . . . . . . . . . . . . . . . . 21

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

Epilepsy Board Review Manual

Seizures and Epilepsy:

effects, and therapeutic monitoring of antiseizure

www.turner-white.com Epilepsy Volume 1, Part 1 1

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

conversion symptoms and dissociative states. Many

Nature of epileptic seizures and

The paroxysmal depolarization shift (PDS) is

underlies all types of epileptic seizures (Figure 1)

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

can be based on intrinsic neuronal properties,

Experimentally induced seizures and animal

www.turner-white.com Epilepsy Volume 1, Part 1 3

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

study the nature of seizures and epilepsy and to

epilepsy models, as do genetic rodent models of

The starting point in diagnosis of seizures and

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

generate a hypothesis regarding the type(s) of

Types of nonepileptic seizures

Organic nonepileptic seizures are paroxysmal

www.turner-white.com Epilepsy Volume 1, Part 1 5

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

described to the neurologist by the patient and

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

Table 2. ILAE 2010 Classification of Seizures

History, examination, and laboratory

The common risk factors, historical associations,

ing event followed by a latent period (during which

www.turner-white.com Epilepsy Volume 1, Part 1 7

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

Movements during period

Epileptic seizure types

Bilateral, repetitive, rapid

Sudden fall or droop, without jerking or shaking

Event with Automatisms Motionless Event

REM behavior disorder

Psychogenic fugue state

epilepsy syndrome (see Heconvulsion-HemiplegiaEpilepsy section below).

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

www.turner-white.com Epilepsy Volume 1, Part 1 9

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

Classification of epilepsies and

There are many highly individual aspects of the

etiology who had indirect evidence of having had

Ongoing efforts to improve epilepsy classification

Specific syndromes of epilepsy

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

www.turner-white.com Epilepsy Volume 1, Part 1 11

Epilepsy and Seizures: Pathophysiology and Diagnostic Principles

Infancy onset group

Childhood onset group

Less specific age relationship

Epilepsies that do not fit into any of these diagnostic categories

Benign neonatal seizures (BNS)

diagnostic criteria by (1) seizure types, (2) age

regarding (4) associated cerebral and systemic