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Review Article

Diagnosis of Epilepsy
Address correspondence to
Dr Gregory D. Cascino,
Department of Neurology,

and Related Episodic


Mayo Clinic, 200 First Street
SW, Rochester, MN 55905,
gcascino@mayo.edu.

Disorders
Relationship Disclosure:
Dr St. Louis receives research
support from the Mayo
Foundation and the National
Institutes of Health.
Erik K. St. Louis, MD, MS, FAAN; Gregory D. Cascino, MD, FAAN Dr Cascino serves on the
board of directors of the
American Academy of
Neurology and as an associate
ABSTRACT editor of Neurology.
Purpose of Review: This review identifies the diverse and variable clinical presenta- Dr Cascino receives royalties
tions associated with epilepsy that may create challenges in diagnosis and treatment. from Mayo Medical Ventures
and UpToDate, Inc.
Recent Findings: Epilepsy has recently been redefined as a disease characterized by Unlabeled Use of
one or more seizures with a relatively high recurrence risk (ie, 60% or greater Products/Investigational
likelihood). The implication of this definition for therapy is that antiepileptic drug Use Disclosure:
Drs St. Louis and Cascino
therapy may be initiated following a first seizure in certain situations. report no disclosures.
EEG remains the most commonly used study in the evaluation of people with * 2016 American Academy
epilepsy. Routine EEG may assist in diagnosis, classification of seizure type(s), of Neurology.
identification of treatment, and monitoring the efficacy of therapy. Video-EEG
monitoring permits seizure classification, assessment of psychogenic nonepileptic
seizures, and evaluation of candidacy for epilepsy surgery. MRI is pivotal in eluci-
dating the etiology of the seizure disorder and in suggesting the localization of
seizure onset.
Summary: This article reviews the new International League Against Epilepsy practical
clinical definition for epilepsy and the differential diagnosis of other physiologic
paroxysmal spells, including syncope, parasomnias, transient ischemic attacks, and
migraine, as well as psychogenic nonepileptic seizures. The initial investigational
approaches to new-onset epilepsy are considered, including neuroimaging and
neurophysiologic investigations with interictal and ictal video-EEG. Neurologists should
maintain a high index of suspicion for epilepsy when children or adults present with a
single paroxysmal spell or recurrent episodic events.

Continuum (Minneap Minn) 2016;22(1):1537.

INTRODUCTION The initial diagnostic approach to


Epilepsy is one of the most common the patient with epilepsy and related
and disabling public health problems, episodic disorders has importance for
affecting approximately 3 million both long-term prognosis and treat-
Americans and an estimated 50 million ment, including the determination of
people around the world.1 Modern
whether treatment is necessary and
diagnostic testing and evolving thera-
the type(s) of therapy to be consid-
pies have transformed care for people
with epilepsy. All neurologists need to ered. When evaluating a patient with
be intimately familiar with epilepsy possible epilepsy, the basic approach
because of its high prevalence, its is as follows: Is this epilepsy, and, if so,
variable and diverse clinical mani- is it focal or generalized? Once a
festations, and the current use of seizure is determined to be a manifes-
antiepileptic drugs (AEDs) for neuro- tation of epilepsy, a diagnostic workup
psychiatric disorders. must be performed to understand the
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Diagnosis of Epilepsy

KEY POINTS
h All neurologists need to underlying cause(s) and epilepsy syn- clinical, electroencephalographic, or neu-
be intimately familiar with drome type when possible. These basic roimaging tests that a heightened risk [at
epilepsy because of its considerations then determine which least 60%] exists for future seizures over
high prevalence, its diagnostic investigations are needed and the next 10 years), or when an epilepsy
variable and diverse the subsequent therapeutic approach. syndrome is diagnosed.2 This new defi-
clinical manifestations,
The basic goals of treatment for epilepsy nition recognizes the practical impor-
and the current use of tance of treating some patients after a
antiepileptic drugs for
are to help the patient achieve freedom
single seizure, since they may also ex-
neuropsychiatric disorders. from further seizures without adverse
perience the consequences of epilepsy,
h Seizures are typically effects of therapies, or at least minimize such as lower quality of life, loss of psy-
paroxysmal and the frequency of disabling or potentially chosocial functioning, and injury.3
episodic, resulting in a injurious seizure types when seizure The principal clinical symptoms and
suddenly occurring but freedom is not achieved, and to address signs of epilepsy include ictal (during a
transient behavioral, any relevant interictal comorbidities of seizure), postictal (immediately following
somatosensory, motor, epilepsy to maximize quality of life for seizure termination), and interictal (be-
or visual symptom or
people with epilepsy. Thus, these goals tween seizure episodes) manifestations.
sign, and caused by
abnormally excessive should guide the diagnostic approach Behavioral alterations accompanying epi-
cortical neuronal activity. to people with epilepsy for overall suc- leptic seizures are diverse, ranging from
cessful management. subjective feelings reported by the pa-
h The International
tient to objectively witnessed behavioral
League Against Epilepsy
adopted a new practical PRACTICAL DEFINITION OF arrest, unresponsiveness, or involuntary
definition for epilepsy EPILEPSY movements. The nature of the ictal
as a disease with either Seizures are typically paroxysmal and behavioral disturbance depends upon
recurrent seizures episodic, resulting in a suddenly occur- the location of seizure onset in the brain
(ie, two or more ring but transient behavioral, somato- and its rate and pattern of propagation
unprovoked seizures sensory, motor, or visual symptom or involving neuronal networks in neigh-
occurring at least sign, and caused by abnormally exces- boring or distant brain regions.
24 hours apart) or a sive cortical neuronal activity. Seizures
heightened tendency
may be provoked by certain influences DIAGNOSIS OF SEIZURE TYPE
toward recurrent AND EPILEPSY SYNDROME
(eg, trauma, brain hemorrhage, meta-
unprovoked seizures
bolic dyscrasias, or drug exposures) or A seizure is a symptom resulting from an
(ie, a single seizure,
occur spontaneously without provo- underlying brain lesion or dysfunction
accompanied by evidence
that a heightened risk cation. Some individuals may have that is not specific for a particular etio-
for future seizures exists), recurrent provoked seizures without logic cause. Diverse causative pathologies
or when an epilepsy having epilepsy, which instead re- can result in similar ictal behaviors and
syndrome is diagnosed. quires that a heightened tendency EEG manifestations. The prognosis and
h The principal clinical toward spontaneous recurrent seizures treatment of a person with epilepsy are
symptoms and signs of is present. Provoked seizures do not directed by the diagnosis of his or her
epilepsy include ictal recur when provoking factors are al- epilepsy syndrome (Case 1-1). Seizure
(during a seizure), tered or corrected. type and epilepsy syndrome diagnosis
postictal (immediately In 2014, the International League are based on a description of seizure
following seizure Against Epilepsy (ILAE) adopted a new behavior and EEG manifestations, fur-
termination), and practical definition for epilepsy as a ther aided by neuroimaging and genetic
interictal (between seizure disease with either recurrent unprovoked investigations in some cases.
episodes) manifestations. seizures (ie, two or more unprovoked Traditionally, epilepsy syndromes
seizures occurring at least 24 hours apart) have been classified as partial, general-
or a heightened tendency toward recur- ized, or unknown (based on predomi-
rent unprovoked seizures (ie, a single nant seizure type[s]), with parallel
seizure, accompanied by evidence from terminology concerning the epilepsy
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Case 1-1
A 19-year-old man with a family history of epilepsy in his father and paternal first cousin presented following
a first apparent seizure. He had just completed his firstYsemester final examinations as a college freshman and
for 2 weeks had been repeatedly sleep deprived. After his last examination, he spent the night celebrating
with friends and drank four beers, although his custom was to have only one or two alcoholic beverages per
week. He awoke the following morning with a slight headache but no other symptoms. After his morning
shower, his roommate said he fell, then stiffened, and his body convulsed for 1 or 2 minutes. He had bitten
his tongue and lost control of his bladder. He remembered nothing until recovering in the emergency
department 2 hours later. Noncontrast head CT was normal, as were serum electrolytes and complete blood
count. He was not started on any specific therapy and was released to home after recovery with a prompt
neurologic consultation arranged. One week later, he was seen in the neurology clinic. Further history was
elicited, and he mentioned a 3-year history of intermittent arm jerking episodes after awakening in the
morning. When he was 15 years old, after arising earlier than usual to deer hunt with his father, he dropped his
rifle when his arm involuntarily jerked, and several times a year, he would twitch and spill his breakfast coffee.
EEG (Figure 1-1) showed generalized atypical spike-and-wave discharges. The patient was diagnosed with
juvenile myoclonic epilepsy and started on divalproex sodium 500 mg 2 times a day. On this regimen,
he remained seizure free and without recurrence of morning arm jerking episodes 1 year later.

FIGURE 1-1 EEG, showing generalized atypical spike-and-wave discharges, of the patient in Case1-1, who had myoclonic
seizures and a first tonic-clonic seizure consistent with juvenile myoclonic epilepsy. Average referential montage.

Continued on page 18

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Diagnosis of Epilepsy

Continued from page 17


Comment. This patient presented following an apparent first generalized tonic-clonic seizure.
His presentation during teenage years, history of other subtler habitual clinical myoclonic seizures,
provocation by recent sleep deprivation and alcohol binge, and generalized epileptiform EEG pattern
were all features consistent with an epilepsy syndrome diagnosis of juvenile myoclonic epilepsy. It is
important to take a thorough history to understand whether patients may have a history of other
spells that signify previous seizures, enabling an earlier diagnosis of epilepsy and prompt treatment of
this lifelong epilepsy syndrome.

KEY POINTS etiology as either idiopathic (having an even many epilepsy practitioners.8
h The prognosis and unknown but often presumed to be ge- Therefore, familiarity with both classifi-
treatment of a person netic cause), cryptogenic (unknown, but cation schemes is preferred until a de-
with epilepsy are directed with a likely causative pathology that finitive classification system is accepted.
by the diagnosis of his or
has not yet been identified), or symp- Differentiating seizure types is often
her epilepsy syndrome.
tomatic (the etiology is known, and the difficult in new-onset seizures. Many
h In the 2010 revised brain is disordered or diseased before partial/focal seizures present clinically as
International League or between seizure episodes). generalized tonic-clonic seizures without
Against Epilepsy
However, in 2010, a revision in sei- apparent focal features, and patients
classification scheme,
zure classification was proposed.4,5 Over- may present after a single seizure or a
seizures are divided into
focal (involving brain
all, the newer proposed nosology is quite limited number of seizures, so the full
networks confined to similar to the traditional 1981 seizure6 range of seizures and related behaviors
one hemisphere) or and 1989 epilepsy7 classification schemes enabling diagnosis in a patient may have
generalized (beginning and reflects advancements in the un- not fully evolved or developed.
in bilaterally distributed derstanding of epilepsy as a brain net- In the traditional terminology, partial
networks synchronously work disorder demonstrated by basic seizures are further classified as simple,
in both hemispheres science, neuroimaging, neurophysiol- complex, or secondarily generalized. Sim-
from onset). ogy, and genetic research.4,5 In the 2010 ple partial/focal seizures do not impair
revised ILAE classification scheme, sei- consciousness and may involve very small
zures are divided into focal (involving volumes of brain tissue with limited
brain networks confined to one hemi- network involvement, equivalent to the
sphere) or generalized (beginning in older term aura but involving a range of
bilaterally distributed networks syn- possible symptoms depending on loca-
chronously in both hemispheres from tion of onset so that autonomic, cogni-
onset).4,5 Some of the proposed termi- tive, emotional, somatosensory, visual,
nology, however, is cumbersome (eg, or involuntary motor activity can occur.
focal dyscognitive seizures instead of TemporalY or extratemporalYonset com-
the older term complex partial seizures, plex partial/focal seizures typically in-
meant to reflect alteration of conscious- volve impaired or altered consciousness
ness in association with a focal/partial and can cause behavioral arrest; staring;
seizure type). A modification of the and oral or manual limb automatisms
proposed classification uses the term such as chewing or swallowing, lip
focal seizure with loss of awareness smacking, vocalization, and aimless
for this seizure type. The specific ictal fumbling hand movements; they are
behavior should also be included in usually accompanied by amnesia. As the
the seizure classification (eg, focal mo- seizure propagates, head turning and
tor seizure). The newer classification limb posturing are frequent. Head turn-
may not be well understood by people ing is most often toward the seizure
with epilepsy, neurology trainees, or focus initially (ipsiversive), followed by

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head or body/trunk deviation away from
the seizure focus late in the course TABLE 1-1 Typical Partial/Focal
(versive turning).9 Limb posturing may Seizure Characteristics
(if Present) According to
be asymmetric, involving a still and dys- Region of Seizure Onset
tonic hand posture contralateral to the
seizure focus and a hand/arm with mo- Partial/Focal
bile automatisms ipsilateral to the focus. Region of Seizure
Extratemporal focal seizures more often Onset Characteristics
have prominent axial and proximal limb Frontal Focal clonic
movements, leading to patient mobiliza- motor
tion, possible falls, and bizarre violent Hypermotor
limb movements that may be misdiag- behavior
nosed as psychogenic (so-called hyper-
Temporal
kinetic or hypermotor seizures), and
more frequently arise from the sleep Mesial Autonomic
state. Variability in behavioral character- Dysmnesic
istics is seen both within and across in-
Dj vu
dividuals with seizure behaviors. Focal
seizures may secondarily generalize, with Jamais vu
the arm contralateral to the side of sei- Gustatory
zure onset extending while the ipsilat- Olfactory
eral arm is often held flexed at the elbow,
making a figure 4 sign.9 Table 1-1 sum- Lateral/ Auditory
posterior
marizes characteristics of partial/focal sei- neocortical
Complex
zures. Infants may also display a range of visual
other potential seizure types, including Dysphasia
spasms (myoclonic/astatic attacks result-
Parietal Somatosensory
ing in head nodding and axial flexion or
collapse, frequently with arm extension) Occipital Simple visual
and other behaviors.10,11 For more in-
formation on pediatric seizures, refer to
the article Infantile, Childhood, and muscles, usually with preserved con-
Adolescent Epilepsies by Elaine Wirrell, sciousness. Massive myoclonus involv-
MD,12 in this issue of Continuum. ing the trunk may lead to falls and
The range of generalized seizure types injury. Tonic seizures involve sustained
includes absence, atonic/astatic, tonic, abnormal posturing of the extremities
myoclonic, clonic, or tonic-clonic sei- caused by cocontraction of agonist and
zures. Absence seizures, frequently pre- antagonist musculature, usually less than
viously called petit mal seizures, are brief 15 seconds in duration, with or without
(less than 10 seconds in duration) epi- vocalization, apnea, and falling. Atonic
sodes involving behavioral arrest, staring seizures (also known as astatic seizures)
with unresponsiveness, and automa- cause loss of muscle tone and falling.
tisms, but unlike focal seizures they Clonic seizures are repetitive jerking
lack any premonitory aura symptoms movements, and generalized tonic-clonic
or postictal state. Frequently, absence seizures involve an initial tonic posturing
attacks may be precipitated in the office phase followed by clonic limb move-
or EEG laboratory by hyperventilation. ments lasting 1 to 3 minutes, usually
Myoclonic seizures involve sudden brief followed by several minutes of postictal
jerks or twitching of limb or axial stupor, confusion, and language or motor

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Diagnosis of Epilepsy

KEY POINTS
h The most common dysfunction (often called Todd paralysis quent compared to epileptic seizures.
non-neurologic disorder [or Todd paresis] when lateralized or Cardiogenic causes of syncope result
mimicking epilepsy localized weakness of limbs is present, from bradyarrhythmia or tachyarrhyth-
is syncope. which can mimic an acute stroke when mia and less frequently involve long
h Several paroxysmal individuals present following an unwit- prodromes. Orthostatic hypotension re-
neurologic disorders can nessed seizure event). Loss of bladder sults from a fall in blood pressure fol-
be confused with or bowel continence and tongue lacer- lowing a positional change to standing
epilepsy, including ation from biting are frequent. from a recumbent position and is a fre-
nonepileptic behavior in quent cause of syncope in patients who
cognitively impaired DIFFERENTIAL DIAGNOSIS OF are elderly or diabetic with autonomic
individuals, transient SEIZURES AND RELATED neuropathy. EEG during a syncopal
ischemic attacks from EPISODIC DISORDERS event most often shows generalized
cerebrovascular disease, The differential diagnosis of epilepsy is slowing or suppression if cerebral blood
delirium, migraines, wide, since several paroxysmal disorders flow is substantially interrupted for a
and movement and
may closely mimic an epileptic seizure. period of 20 to 30 seconds, often re-
sleep disorders.
Table 1-2 details common nonepileptic sulting when asystole occurs during
paroxysmal spells and the seizure types severe vasovagal attacks.
they most closely resemble by behav-
ioral characteristics, duration, and usual Neurologic Differential Diagnoses
EEG findings. Nonepileptic spells can be Several paroxysmal neurologic disorders
divided into two basic categories, phys- can be confused with epilepsy, including
iologic and psychogenic. Physiologic nonepileptic behavior in cognitively im-
nonepileptic spells include a diversity of paired individuals, transient ischemic
non-neurologic and neurologic etiologies. attacks (TIAs) from cerebrovascular dis-
ease, delirium, migrainous events, and
Non-neurologic Differential movement and sleep disorders. Individ-
Diagnosis uals who are cognitively impaired are
The most common non-neurologic dis- especially prone to be overdiagnosed
order mimicking epilepsy is syncope. with epilepsy or to have nonepileptic
Syncope most frequently results from behavioral spells complicating true epi-
cardiogenic, vasovagal (often called sim- lepsy. Examples of nonepileptic behav-
ple faints), or hypotensive causes.13 ioral spells in this patient population
Vasovagal/neurocardiogenic syncope is include staring with unresponsiveness
the most common of these and is a and movements mistaken for epileptic
generally benign form of syncope char- automatisms (eg, stereotypies, manner-
acterized by prodromal subjective isms, or tardive dyskinesia). When be-
symptoms of lightheaded dizziness, havior presumed to be seizure related
diaphoresis, and nausea, often provoked fails to respond to AED treatment,
by triggers such as positional change, video-EEG monitoring may be neces-
physical exertion, Valsalva maneuvers sary to classify nonepileptic and epilep-
(eg, lifting, toileting), or strong emo- sy-related behaviors. Patients with drug-
tional triggers (eg, the sight of blood). resistant epilepsy (ie, refractory to two
Loss of consciousness is often brief, or more AEDs) should also undergo
lasting seconds to a few minutes. Con- epilepsy monitoring for classification
vulsive movements are frequent dur- and possible surgical localization.
ing syncopal attacks, leading to further Cerebrovascular disease. Cerebro-
diagnostic confusion with epilepsy. Con- vascular disorders also can present with
fusion and loss of continence following paroxysmal cerebral dysfunction resem-
recovery of consciousness are infre- bling seizures. Clinical characteristics
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TABLE 1-2 Differentiating Seizures From Nonepileptic Spells

Type of
Paroxysmal Premonitory Spell Usual Postspell
Event Symptoms Characteristics Duration Symptoms
Absence seizure None Staring, G10 seconds None
automatisms
Focal seizure with Variable aura Staring, 30Y180 seconds Common;
loss of awareness or brief automatisms, amnesia,
(complex partial (10Y30 seconds) variably preserved aphasia,
seizure) sensory march posture sleepiness,
confusion,
variable
incontinence
Tonic-clonic Aura variable Brief tonic 1Y3 minutes Requisite;
seizure posturing, amnesia,
ensuing clonic sleep,
movements incontinence,
tongue
biting/injury
Psychogenic Variable Variable Often prolonged Variable,
spell/attack responsiveness, (95Y10 minutes) often none
nonstereotyped,
unusual movements
Syncope Frequent: Falling, eye closure, 1Y5 minutes Variable,
lightheaded, variable movements often none
dizziness
Migraine Prolonged sensory Often positive 20Y60 minutes Headache
march (minutes) symptoms (eg,
paresthesia,
photopsia)
Transient Rapid sensory march Often negative G60 minutes None
ischemic attack (1Y10 seconds) symptoms (eg, dead
numbness, weakness)
Parasomnia None Vocalization, Minutes Amnesia,
confusion, confusion
ambulation
Cataplexy Emotional Muscle atonia, Seconds to None
provocation preserved minutes
consciousness or
sleep attack

depend on the duration of ischemia radiographic evidence for infarction.


and the arterial territory involved, and, Cerebrovascular disorders more fre-
as with seizures, a diversity of clinical quently cause negative symptoms,
symptoms may result depending on such as numbness, weakness, visual
anatomic localization. TIAs typically loss, or aphasia, compared to epileptic
last from minutes to 1 hour, although seizures. Epileptic seizures more often
prolonged TIAs are likely to show involve positive symptoms and signs

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Diagnosis of Epilepsy

during the ictal event, although post- resulting in further diagnostic confu-
ictal negative signs, including aphasia sion. In delirious patients, EEG most
and hemiparesis, frequently complicate often shows diffuse nonspecific non-
seizures, leading to diagnostic confu- epileptiform background slowing or
sion with stroke. However, repetitive even epileptiform-appearing patterns
limb-shaking convulsive movements such as diffuse triphasic waves.
(so-called limb-shaking TIAs); other Migraine. Clinical manifestations of
abnormal movements such as hemi- migraine and epilepsy are often similar,
ballismus, chorea, or dystonia; or even involving visual, sensory, and cognitive
symptomatic seizures from irritation symptoms. Migrainous headaches often
of neighboring cerebral cortical tissue follow epileptic seizures, and seizures
may all follow acute ischemia, leading following a primary migraine may oc-
to diagnostic uncertainty in some cur. However, in most patients, despite
cases.14 Ictal video-EEG monitoring similar clinical characteristics, migraine
is sometimes helpful in differentiating and epilepsy have distinct mechanisms.
TIAs from seizures, since focal cerebral During a migraine attack, EEG demon-
slowing or normal findings are seen on strates focal or generalized slowing, as
EEG during TIAs or stroke (typically poly- opposed to partial seizures, which may
morphic delta activity), distinguished show focal evolving rhythmic activity.
from the focal evolving rhythmic activity Movement disorders. Movement dis-
accompanying most partial seizures. orders, including paroxysmal dystonias
Encephalopathy. Delirium (enceph- and dyskinesias and some tremor dis-
alopathy) is a state of generalized confu- orders, may also resemble epileptic sei-
sion caused by a systemic disorder, often zures. EEG is invariably normal during
occurring when a vulnerable patient subcortically generated movement dis-
with an underlying mild cognitive im- orders. Careful observation of clinical
pairment or dementia is subjected to phenomenology is necessary to distin-
a procedure; change in medication; or guish these episodes from seizures, since
new acute change associated with sys- simple partial motor seizures may also
temic infection, inflammation, or expo- demonstrate stereotyped movements
sure to toxins or a metabolic disturbance, lacking an EEG change.
such as acute evolving hepatic or renal Sleep disorders. Nocturnal events
impairment.15 The hallmarks of deliri- confused with sleep epilepsies include
um are disorientation and inattention; the nonYrapid eye movement (REM)
patients are acutely disoriented, unable parasomnias (disorders of arousal) and
to accurately name their current loca- REM sleep behavior disorder.16 Non-
tion or the date, and incapable of con- REM parasomnias involve a spontaneous
centrating well enough to execute serial arousal from non-REM sleep, usually
calculations or spell words backward. from N2 or N3 (slow-wave) sleep, with
The clinical phenomena of confusion in nonstereotyped confused behavior
a delirious state may closely resemble with or without vocalization or sleep-
ictal or postictal behavior associated walking behavior. EEG may show no
with a complex partial/focal seizure, in- change other than arousal but oc-
volving staring with disorientation, inat- casionally shows generalized or frontal
tention, and variable responsiveness; dominant rhythmic delta or theta pat-
stupor with reduced vigilance; and un- terns lasting a few seconds following
usual movements, including myoclonic the arousal. REM sleep behavior disor-
jerks. Encephalopathic patients may also der is characterized by complex motor
have acute symptomatic seizures, behavior paralleling dream content,
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KEY POINT
causing enactment of the dream. Be- duration (ie, often much longer than h Psychogenic nonepileptic
haviors are often violent as patients may 1 minute). Typical features of PNES may seizures are behavioral
dream of being attacked or chased, and closely resemble actual epileptic seizures, events closely resembling
while in their dream they are defending including unresponsiveness, abnormal epileptic seizures
themselves, they may injure themselves movements, and postictal-type behavioral but lacking the
or a bed partner by punching, kicking, alteration. However, PNES can be distin- typical clinical and
or falling out of bed. Polysomnography guished by eye closure during the spell electrophysiologic
is necessary for diagnosis, showing (which may rarely be seen in true epileptic features of true epilepsy.
frequent rapid phasic muscle jerks and seizures as well) and often bizarre volun-
heightened chin and limb muscle tone tary movements, including yes-yes type
during REM sleep. head nodding or no-no type side-to-side
In distinction, nocturnal seizures head shaking, prominent pelvic thrust-
demonstrate highly stereotyped com- ing, or atypical nonanatomic spread of
plex motor behavior, frequently with movements (eg, clonic-type move-
oral, limb, or trunk automatisms. Sei- ments that may begin in a leg, spread
zures of temporal lobe origin show to the head, then to an arm, features
prominent focal evolving rhythmic activ- that also may occur in true epilepsy).
ity, while frontal lobe seizures often Moreover, individual PNES lack stereo-
show little demonstrable ictal EEG typy across different events. The hall-
change that is often obscured by muscle mark of PNES is the lack of an ictal
and movement artifact; diagnosis relies epileptiform EEG discharge. However,
upon observation of stereotyped typical caution and considerable experience are
hypermotor behaviors. Cataplexy accom- necessary to accurately diagnose PNES,
panying narcolepsy may occasionally be as epileptic seizures may share many
difficult to distinguish from astatic sei- similar atypical clinical characteristics
zures but is usually easily distinguished by and lack an EEG change. When diagnos-
characteristic emotional provocation, es- tic confusion remains, patients should
pecially following laughter or anger. undergo ictal video-EEG monitoring to
Diagnosis can be made with confidence ensure an accurate diagnosis, which can
upon observing an episode and demon- be accomplished in most cases within
strating reversible loss of knee muscle 2 to 3 days of admission to an epilepsy
stretch reflexes during an attack, followed monitoring unit. For more information
by recovery of reflexes between attacks. on PNES, refer to the article Diagnosis
Nonepileptic behavioral events. and Treatment of Nonepileptic Seizures
Psychogenic nonepileptic seizures by David K. Chen, MD, and W. Curt
(PNES) are frequent sources of confu- LaFrance Jr, MD, MPH, FAAN, FANPA,
sion with epileptic seizures.17,18 PNES DFAPA,19 in this issue of Continuum.
are behavioral events closely resem-
bling epileptic seizures but lacking the INVESTIGATION OF THE PATIENT
typical clinical and electrophysiologic WITH SEIZURES AND SPELLS
features of true epilepsy. PNES are espe- The emphasis for patients with new-onset
cially common presentations in epilepsy seizures or spells is prompt diagnosis and
monitoring unit practices, accounting an evaluation to determine the underlying
for 30% to 50% of admissions. Ictal etiology. Diagnostic tests also help deter-
video-EEG telemetry remains the gold mine the epilepsy syndrome diagnosis
standard for diagnosis. Patients with and help determine the prognosis for
PNES are less likely to have abnormal future seizure recurrence. After a detailed
EEGs or MRI scans prior to admission history is taken from the patient and any
and more often have prolonged spell available collateral historians, investigation
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Diagnosis of Epilepsy

KEY POINTS
h When the EEG shows an with EEG and neuroimaging is essential or spike-wave discharges that are dis-
epileptiform discharge to consider in the evaluation of most tinct from the normal background
after a single seizure, patients presenting with seizures or spells activity and indicate an increased sei-
treatment may be and is an expected consideration within zure tendency. The spike discharges
considered even before a the American Academy of Neurology are predominantly negative transients
diagnosis of epilepsy (AAN) Epilepsy Quality Guidelines.20 with steep ascending and descending
is established. limbs and a duration of 20 ms to 70 ms.
h The sensitivity of a single Electroencephalography A sharp wave is a broader potential with
EEG study to record an The EEG is the most commonly a duration of 70 ms to 200 ms. The
epileptiform abnormality performed diagnostic study in people epileptiform discharges should be dis-
may be 50% or less in with epilepsy. The first EEG performed tinct from the normal background activity,
people with epilepsy. on a person was recorded by Hans involve more than one scalp electrode,
Berger in 1924, and the importance of and have a physiologic field, and a voltage
EEG in the evaluation of patients with gradient should be present. Knowledge
epilepsy was confirmed by several in- about the patients age, coexistent medi-
vestigators in the 1930s. The EEG has cation uses, state of consciousness, and
enhanced our understanding of the patho- medical history are needed to appro-
physiology of seizures and has been an priately interpret the EEG study. The
invaluable diagnostic tool in the evalua- conceptual age of the patient is impor-
tion and treatment of seizure disor- tant for neonatal recordings. An epilep-
ders.20,21 Early observations concerning tiform pattern seen on EEG after a
the use of EEG in epilepsy validated the first-time seizure often predicts recur-
basic tenets outlined by J. Hughlings rence of seizures based on studies in
Jackson and his colleagues in the 19th both adults and children, with recur-
century regarding cortical excitability and rence rates that range from 30% to 70%
hypersynchrony in focal seizures.22 in the first year.24 Therefore, when the
The routine awake and asleep EEG EEG shows an epileptiform discharge
recording may be obtained on an outpa- after a single seizure, treatment may be
tient or inpatient basis and includes considered even before a diagnosis of
activating procedures, such as eye open- epilepsy is established.
ing and eye closure, hyperventilation, The clinical applications of EEG in-
and photic stimulation. The importance clude diagnosis of epilepsy, selection of
of sleep deprivation and the performance AED therapy, evaluation of response to
of the EEG recording during sleep in treatment, determination of candidacy for
patients with epilepsy have been empha- drug withdrawal, and surgical localization.
sized.23 In selected patients, the epilep- Sensitivity and specificity. The sen-
tiform discharges may only be present sitivity of a single EEG study to record
during the sleep EEG recording. The an epileptiform abnormality may be
AAN recommends EEG in diagnosing 50% or less in people with epilepsy.23Y25
epilepsy in adults and children, with The diagnostic yield increases to 80% to
inclusion of photic stimulation, hyper- 90% if three or more serial EEGs are
ventilation, and sleep deprivation in performed.26 Patients with childhood
adults as part of the protocol.20 EEG epilepsy are more likely to have abnor-
studies may reveal interictal epilepti- mal epileptiform EEG recordings than
form abnormalities. Repetitive EEGs adult patients. The timing of the EEG in
may be of diagnostic importance and relationship to a clinical seizure also in-
may evaluate the patients response to creases the likelihood of recording a
therapy. Epileptiform abnormalities specific epileptiform pattern.20,21 The
usually appear as spikes, sharp waves, presence of an epileptiform discharge
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KEY POINT
suggests a significant epileptogenic po- barriers to recording the EEG include h Normal interictal EEG
tential and indicates a high specificity CSF, dura, bone, and scalp, and these studies do not exclude
for these paroxysmal findings. Normal noncerebral tissues intervening between the presence of a
interictal EEG studies do not exclude the brains surface and recording elec- seizure disorder.
the presence of a seizure disorder. Ulti- trodes produce a marked attenuation of
mately, epilepsy is a clinical diagnosis spontaneous cortically generated EEG
and the EEG serves to provide support- activity. Extracranial (scalp) EEG records
ing evidence; in other words, you treat activity in only approximately one-third
the patient and not the EEG. Interictal of the cerebral cortex. Scalp EEG may
epileptiform discharges are seen rare- not record potentially epileptiform dis-
ly in adults or children without epilepsy charges in basal regions, sulci, medial
(0.2% to 3%).27 Epileptiform abnormali- temporal lobe, and interhemispheric
ties were detected very uncommonly in regions. Simultaneous extracranial and
healthy airline personnel who under- intracranial EEG recordings show that
went EEG studies.28 Other factors that only 10% to 15% of intracranial spikes
may affect the diagnostic yield of EEG in are detected with scalp EEG studies.29
patients with epilepsy include: (1) the Routine EEG conventionally samples
age of the patient (children often have a narrow bandwidth of frequencies
more frequent interictal spiking or re- (0.5 Hz to 70 Hz); brain frequency ac-
corded seizures); (2) seizure classifica- tivity is much broader.
tion and epileptic syndrome diagnosis The presence of artifacts is a con-
(patients with primary generalized sei- stant concern in the interpretation of
zures and epilepsies usually have higher the EEG. These may include electrode
yield of diagnostic interictal changes popping, high electrode impedance,
on EEG); (3) presence of AED therapy and other technical and environmen-
(which can decrease the yield for tal factors. Physiologic changes associ-
interictal discharges); and (4) proximity ated with head movement, tremor, eye
of the EEG recording to seizure activity opening and closure, sweating, nystag-
(since patients with more recent sei- mus, and myogenic activity may be
zures more frequently have diagnostic difficult to differentiate from epilepti-
EEG recordings). form discharges. The EEG study is usually
The presence of an epileptiform brief, approximately 20 to 40 minutes,
abnormality does not always indicate a and may fail to identify epileptiform
seizure disorder. Occipital spikes have alterations in people with epilepsy. At
been observed in blind people, and least 6 cm2 of cerebral cortex must be
generalized spikes have been reported involved to generate a scalp-recorded
in relatives of patients with genetic gen- epileptiform discharge.29
eralized epilepsies. Interictal epilepti- When EEG alterations are seen, the
form discharges may also be seen in routine EEG study almost invariably re-
patients receiving bupropion, cefepime, cords interictal EEG alterations because
clozapine, lithium, and tramadol, and in of the paroxysmal nature of the sei-
individuals with certain metabolic disor- zures.20,21,23 Recognition of the ictal
ders such as patients with renal failure EEG pattern (ie, during the seizure)
or an acute encephalopathy. may be necessary to confirm the diag-
Limitations. The limitations associ- nosis of a seizure disorder and to sug-
ated with routine EEG are significant gest seizure type(s). In many patients,
and have been known since the initial interictal epileptiform activity may prove
studies of this diagnostic tool in people sufficient to select the appropriate treat-
with epilepsy (Table 1-3). Physiologic ment. The sensitivity and specificity of
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Diagnosis of Epilepsy

TABLE 1-3 Diagnostic Use of EEG Recordings

Factors Beneficial Features Limitations


Duration of study Brief (G60 minutes) Low to moderate diagnostic
sensitivity given limited
recording duration and single
sampling point in time
Location Outpatient or inpatient None
Patient age Children or adults Maturational effects of EEG
may be difficult to interpret,
patient cooperation
required for EEG
Video monitoring Outpatient or inpatient availability, Higher cost, inpatient
actual spell recording with concomitant recordings require intensive
video-recorded behavior and ictal EEG resources and expose patient
is the gold standard for diagnosis of to temporary danger if
spell/seizure type when clinical history antiepileptic drugs
and/or interictal EEG is unclear are discontinued
EEG interpretation Reproducible results, study findings Overinterpretation of
can be compared to prior EEGs, nonspecific findings, normal
highly specific patterns paroxysmal alterations (eg,
drowsiness), benign variants,
medication effects, and
artifacts can be mistaken for
abnormal epileptiform activity

EEG = electroencephalogram.

ictal EEG, however, is superior to mal variants in EEG (eg, benign sporadic
interictal EEG as a diagnostic tool. sleep spikes or wicket waves during
Interictal EEG alone may lead to errors drowsiness or build-up slow waves
in diagnostic classification that result in with intermixed spiky components dur-
an ineffective treatment strategy. The ing hyperventilation) may also be in-
routine EEG may be persistently normal correctly identified as epileptiform
in an individual with epilepsy, even discharges that suggest the diagnosis
with drug-resistant seizure disorders of epilepsy.30 These paroxysmal alter-
(Case 1-2). Paroxysmal alterations (ei- ations are not associated with an in-
ther nonspecific or potentially epilep- creased epileptogenic potential.
tiform discharges) may be identified in Electroencephalography and focal
a patient with nonepileptic behavioral seizures. Focal seizures are the most
events (PNES). The interictal EEG pat- common seizure type in patients with
tern also may be an unreliable indica- epilepsy. The most epileptogenic region
tor of the classification of seizure type. or zone (the area likely to be associated
For example, generalized spike-and-wave with seizures) is the medial temporal
discharges may be present in a patient lobe, including the amygdala and hip-
with a focal seizure disorder; general- pocampus. The majority of patients
ized paroxysmal abnormalities may be with extratemporal focal seizures (ie,
present without well-defined focal alter- seizures emanating outside the tempo-
ation(s). Nonspecific benign and nor- ral lobe) have seizures of frontal lobe

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Case 1-2
A 33-year-old man presented with two recent unprovoked nocturnal
tonic-clonic seizures during sleep in the last 3 months. During one seizure,
he lacerated the lateral aspect of his tongue and had probable urinary
incontinence. The seizures were witnessed by his spouse. The patient
had no history of remote symptomatic neurologic disease. There was no
family history of seizures. The patients medical history was essentially
unremarkable and did not suggest an etiology for his seizures. He was
receiving no medications and denied a history of alcohol or substance
abuse. Neurologic examination was normal. Both a CT and an MRI of
his brain were normal. An awake-asleep EEG with standard activating
procedures was unremarkable.
Comment. This patient would be an appropriate candidate for
antiepileptic drug therapy despite the normal EEG recording. The
probability of a third seizure is sufficiently high to justify empiric therapy
in the absence of a determined etiology or an epileptiform EEG finding.
It is best to treat the patient and not the EEG in this setting.

origin. An extratemporal region of sei- reveal epileptiform discharges.31 The


zure onset can be confirmed in 10% to interictal EEG finding in the patient
30% of patients with focal seizures. with focal seizures is the focal-spike or
Extratemporal seizures are more likely sharp-wave discharge identifying the
associated with EEG studies that do not irritative zone (Figure 1-2). Focal spikes

FIGURE 1-2 EEG of a patient with focal seizures of right frontal lobe origin that reveals right superior frontal (F4) and
midfrontal (Fz) spike discharges during sleep.

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Diagnosis of Epilepsy

KEY POINT
h The sensitivity and or sharp waves are usually asymmetric
and may be bilaterally synchronous, TABLE 1-4 Epileptogenic
specificity of the routine Potential of
EEG in focal epilepsy often followed by a slow wave. They Paroxysmal Discharges
depends on the generally have a radial dipole (formed
localization of the when current flow is perpendicular b High (990%)
epileptic brain tissue, to the scalp). The field of distribution
Anterior temporal lobe spikes
duration of the recording, on a scalp recording depends on the
use of supplementary location of the irritative zone. They Vertex spikes
electrodes, frequency of occur singly but in some cases can be Generalized paroxysmal
seizure activity, and focal polyspikes, and the state during fast activity
timing of the study in
which they appear (ie, awake or asleep) Generalized slow spike
relationship to the most
can vary with the epilepsy syndrome. and wave
recent seizure.
Another interictal EEG pattern is tem- Hypsarrhythmia
poral intermittent rhythmic delta ac-
tivity (TIRDA). The interictal EEG b Moderate (50Y90%)
alterations suggest an increased epilep- Frontal lobe spikes
togenic potential. Epileptiform changes Central-midtemporal spikes
during a routine EEG recording may
Occipital spikes
confirm the classification of the seizure
disorder and suggest the region of Generalized atypical spike
seizure activity in the brain. The most and wave
common interictal EEG finding in adult Photoparoxysmal discharge
patients with focal seizures is the ante- b None
rior temporal lobe spike discharge. The
anterior temporal lobe epileptiform Benign variants
discharge is highly epileptogenic, and Normal sleep activity
80% to 90% of these patients have a Photic driving
seizure disorder (Table 1-4). The sen-
Hyperventilation-induced
sitivity and specificity of the routine
changes
EEG in focal epilepsy depends on the
localization of the epileptic brain tissue Drowsy bursts
(with EEG in patients with temporal
lobe seizures having higher diagnostic
yield than extratemporal seizures), du- poral spikes may not be identified
ration of the recording, use of supple- during routine scalp-recorded EEG
mentary electrodes, frequency of studies. Supplemental scalp electrodes
seizure activity, and timing of the study may prove useful to localize the topog-
in relationship to the most recent sei- raphy of the irritative zone. The diag-
zure. Patients with focal seizures may nostic yield of the EEG in patients with
have generalized or bihemispheric focal seizures depends on multiple
spike discharges that are widely distrib- factors, including the localization of
uted without lateralization, or bilateral the epileptogenic zone.20,21,23Y26 In pa-
independent temporal lobe epilepti- tients with temporal lobe epilepsy, 80%
form alterations. Secondary bilateral to 90% will have predominantly tem-
synchrony has been observed in pa- poral lobe epileptiform discharges.
tients with focal seizures of mesial Bitemporal spike discharges may be
frontal lobe origin. identified in 25% to 33% of patients
Diagnostic yield of electroencepha- with temporal lobe epilepsy. Only ap-
lography in focal seizures. Mesial tem- proximately one-half of patients
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KEY POINT
with extratemporal seizures will have Generalized seizures. The pre-
h Approximately 10% to
interictal epileptiform discharges local- dominant routine EEG abnormality in 30% of patients with
ized to the correct lobe of seizure patients with a genetic generalized focal seizures of
origin. Approximately 10% to 30% of epilepsy is the widely distributed and extratemporal origin
patients with focal seizures of extra- bisynchronous alteration referred to have no interictal
temporal origin have no interictal epi- as the generalized spike-and-wave dis- epileptiform discharges
leptiform discharges on repetitive charge (Figure 1-1).32 The interictal on repetitive routine
routine EEG recordings. A lateralized, epileptiform pattern may be most EEG recordings.
but not localized, interictal abnormality prominent in the anterior or posterior
is the most common routine EEG alter- head region. The epileptiform dis-
ation in patients with extratemporal charge shows no significant lateraliza-
seizures. Patients with mesial frontal tion. Activation of the epileptiform
lobe regions of seizure onset may have abnormality may occur in response to
bisynchronous spike discharges with- selected provocative maneuvers (eg,
out obvious asymmetry. In patients hyperventilation or photic stimula-
with temporal lobe epilepsy, the EEG tion). Typically, absence seizures
pattern is a more reliable indicator of are activated with hyperventilation,
the epileptogenic zone. although epileptiform discharges in
The care and management of pa- focal epilepsies may be activated as
tients with focal seizures is deter- well. Photic stimulation is a useful
mined by the response to therapy method of activating epileptiform dis-
and not necessarily the presence of charges primarily in patients with a
interictal epileptiform discharges after genetic generalized epilepsy, but also
therapy is initiated (Case 1-3). The in those with focal seizures. Photic
use of routine EEG to select candi- driving of a posterior rhythm is a
dates for AED discontinuance is con- normal response, and a photomyogenic
troversial. Other factors, including response that consists of brief repetitive
seizure type, history of remote symp- muscle activity, such as eye blinks seen
tomatic neurologic disorders, difficulty in anterior electrodes that increase in
attaining seizure remission, and seizure- amplitude with flash frequency and
free duration may be more predic- cease when stimulation stops, is a
tive determinants of the success of normal variant. A photoparoxysmal re-
AED discontinuance. sponse (Figure 1-3) that consists of

Case 1-3
A 42-year-old man had a history of recurrent focal seizures. He was seizure
free on a single antiepileptic drug (AED) for over 1 year. The patient was
highly compliant with his medical regimen. He denied drug adverse
effects. He was employed and operating a motor vehicle without difficulty.
A routine EEG that was performed while he was on AED therapy showed
intermittent right temporal interictal epileptiform discharges during sleep.
Comment. This patient has a seizure disorder in remission on AED
therapy. The presence of an interictal epileptiform discharge would not
require a change in medical therapy or an increase in the dose of medication.
The patients performance on his AED therapy (seizure freedom and
without adverse effects) is the best indicator of medication response.
The abnormal interictal EEG study would also not require a change in
his ability to operate a motor vehicle.

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Diagnosis of Epilepsy

FIGURE 1-3 EEG during photic stimulation of a patient with a generalized seizure disorder showing a photoparoxysmal
response. Ipsilateral ear reference montage.

KEY POINT generalized spike-wave or polyspike- types, including myoclonic, generalized


h Seizure type(s), frequency, and-wave discharges, which may be tonic-clonic, and atonic seizures. The
and specific epilepsy anterior or posterior dominant and that interictal EEG pattern in these patients
syndrome are important may or may not be associated with loss reveals slow spike and wave, which
determinants of the of awareness or myoclonic jerks, is an occurs at 1.5 Hz to 2.5 Hz. Patients with
diagnostic yield of
abnormal response often associated pervasive developmental delay may
routine EEG studies in
with epilepsy, especially if it outlasts have increased diffuse slow-wave activ-
patients with a genetic
generalized epilepsy.
the duration of the photic stimulation. ity and disorganization of the EEG
Photoparoxysmal responses are most background. These individuals may have
often seen in genetic generalized epi- Lennox-Gastaut syndrome, associated
lepsies, such as childhood absence epi- with a chronic global encephalopathy,
lepsy with or without eyelid myoclonia, multiple seizure types, and generalized
juvenile absence epilepsy, and juvenile spike-and-wave discharges (Figure 1-4).
myoclonic epilepsy.33 Almost invariably, patients with this un-
Seizure type(s), frequency, and spe- favorable epilepsy have tonic seizures
cific epilepsy syndrome are important with generalized paroxysmal fast activity
determinants of the diagnostic yield of bursts during slow-wave sleep. Patients
routine EEG studies in patients with a with juvenile myoclonic epilepsy and
genetic generalized epilepsy.30 Patients generalized tonic-clonic seizures upon
with childhood absence epilepsy may awakening usually have a normal EEG
have a normal EEG background with the background with intermittent general-
emergence of 2.5-Hz to 3.5-Hz general- ized spike-and-wave discharges and
ized spike-and-wave discharges. Individ- polyspikes (3.5 Hz to 6 Hz).32 These in-
uals with atypical absence seizures are terictal EEG alterations are more likely
more likely to have developmental to occur upon arousal after sleeping
delay and experience multiple seizure and during photic stimulation.

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FIGURE 1-4 EEG revealing generalized slow spike-and-wave discharges and diffuse slowing in a patient with
Lennox-Gastaut syndrome. Ipsilateral ear reference montage.

Video-Electroencephalography cal center.34 The studies may be par- KEY POINTS


Recordings ticularly important in neurocritical care h Indications for video-EEG
units in the assessment of encephalopa- studies include the
Video-EEG monitoring may be used to
evaluation of spells,
evaluate patients with presumed seizure thy and nonconvulsive status epilepticus.
seizure classification,
disorders. In a minority of people with An estimated 25% to 33% of patients
seizure quantification,
epilepsy, video-EEG monitoring is nec- admitted to an epilepsy monitoring unit assessment of seizure-
essary for correct diagnosis prior to AED have nonepileptic behavioral events precipitating factors,
therapy (Figure 1-5). Indications for (PNES) (Figure 1-6).35,36 Spell symp- and surgical localization
these EEG studies include the evaluation tomatology, patient examination by in drug-resistant
of spells, seizure classification, seizure monitoring personnel during the event, focal epilepsy.
quantification, assessment of seizure- and lack of electrographic seizure activity h Spell symptomatology,
precipitating factors, and surgical local- are used to render the diagnosis of a patient examination by
ization in drug-resistant focal epilepsy. nonepileptic disorder. Correct classifi- monitoring personnel
Video-EEG monitoring can be performed cation of a nonepileptic disorder will during the event, and
on an outpatient or inpatient basis or in permit discontinuance of AED therapy lack of electrographic
a specially designed epilepsy monitor- and institution of appropriate medical seizure activity are used
ing unit. Ambulatory studies are now treatment. Only about 9% to 15% of pa- to render the diagnosis
of a nonepileptic disorder.
available that provide digital video-EEG tients with psychogenic events have co-
monitoring at sites remote from a medi- existent seizure disorders.35 Repeat

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Diagnosis of Epilepsy

FIGURE 1-5 Scalp-recorded EEG change during a habitual event showing the onset of a left temporal lobe seizure. This
study was performed in the epilepsy monitoring unit with video-EEG recording. Bipolar montage.

KEY POINTS video-EEG monitoring may be necessary is considered essential in patients under-
h Only about 9% to 15% of if the initial evaluation is indeterminate.37 going a presurgical evaluation.
patients with psychogenic Inpatient video-EEG has several
events have coexistent Magnetic Resonance Imaging
limitations. First, patients may not
seizure disorders.
have a typical or habitual clinical spell The rationale for neuroimaging studies
h Focal seizures without during their inpatient stay. However, a in people with epilepsy includes iden-
loss of awareness, long-term EEG study is still potentially tification of the pathologic findings
especially when of
valuable. Over 80% of people with associated with focal or generalized
extratemporal origin,
epilepsy will have interictal epilepti- seizures, localization of the epilepto-
may not be associated
with a scalp-recorded
form discharges present during 3 days genic zone, and determination of sur-
seizure discharge. of EEG recording. Second, focal sei- gical localization in drug-resistant focal
zures without loss of awareness, espe- epilepsy (Figure 1-7 and Figure 1-8)
h All individuals with
cially when of extratemporal origin, (Case 1-4).38 MRI is the structural
seizures should undergo
an MRI study unless the
may not be associated with a scalp- neuroimaging procedure of choice in
patient has a confirmed recorded seizure discharge. Individuals people with epilepsy.38Y43 Neuroimag-
genetic generalized with supplementary motor area seizures, ing studies are increasingly important
epilepsy syndrome however, typically will have sleepYrelated for the evaluation of patients with recur-
(eg, childhood absence hypermotor seizures. Finally, the cost of rent paroxysmal symptoms suggesting a
epilepsy) or a these studies is substantial. The cost- seizure disorder in the presence of un-
contraindication exists effectiveness of video-EEG monitoring as remarkable or indeterminate routine
that does not permit a diagnostic tool is more difficult to assess EEG studies. All individuals with seizures
this imaging procedure than is the relevant information obtained should undergo an MRI study unless
to be done safely. using these studies. Inpatient monitoring the patient has a confirmed genetic

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FIGURE 1-6 EEG during a psychogenic nonepileptic seizure. A, EEG during psychogenic nonepileptic seizure revealing a
prominent artifact related to muscle activity and movement during the convulsive behavior. B, EEG
immediately after the motor activity has ceased showing a normal awake background without epileptiform
activity. The patient appeared unresponsive at this time. This study was performed in the epilepsy monitoring unit with
video-EEG recording. Bipolar montage.

generalized epilepsy syndrome (eg, Importantly, 12% of patients in one


childhood absence epilepsy) or a con- series of 1013 patients with a first
traindication exists that does not per- seizure had an abnormal MRI head
mit this imaging procedure to be done (specific pathologic alteration) in the
safely. Even individuals with single presence of a normal CT head.39 MRI is
seizure episodes may benefit from an a reliable indicator of selected underly-
MRI study because 29% of these pa- ing pathologies with varying degrees
tients may have abnormal imaging.39 of sensitivity and specificity that are
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Diagnosis of Epilepsy

FIGURE 1-7 Coronal fluid-attenuated inversion recovery (FLAIR)


MRI sequence showing increased signal in the right
hippocampal region. Pathology following epilepsy
surgery revealed mesial temporal sclerosis.

FIGURE 1-8 Sagittal MRI using the double inversion recovery


sequence showing a focal signal change consistent
with bottom-of-sulcus dysplasia (arrow).
Pathology revealed focal cortical dysplasia.

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Case 1-4
A 25-year-old man had a history of recurrent
focal seizures beginning in childhood. He had
nocturnal seizures during sleep associated with
hypermotor activity. His neurologic examination
was normal. Routine EEG revealed only mild
diffuse nonspecific slowing. Video-EEG monitoring
showed a bifrontal ictal discharge that was
lateralized to the right hemisphere. Brain MRI
showed a transmantle sign seen in the
oblique-coronal fluid-attenuated inversion
recovery (FLAIR) sequence (Figure 1-9). The
patient underwent chronic intracranial EEG
monitoring that confirmed the concordance
between the area of seizure onset and the
MRI-identified structural abnormality. The
pathologic findings were consistent with focal
cortical dysplasia. The patient was seizure
free following a focal cortical resection.
Comment. The imaging finding of a
transmantle sign is a specific alteration
that has been shown to be consistent with FIGURE 1-9 Imaging of the patient in Case 1-4. Coronal
focal cortical dysplasia and is associated fluid-attenuated inversion recovery (FLAIR)
MRI sequence showing a focal lesion in the
with a favorable operative outcome in right frontal lobe consistent with the transmantle sign.
patients with drug-resistant focal epilepsy. Pathology revealed focal cortical dysplasia.
MRI was pivotal in this patient to suggest
the area of seizure onset, the underlying
pathology, and an operative strategy.

associated with focal seizures, includ- sclerosis defined on histopathology


ing tumor, vascular malformation, (Figure 1-7). Studies demonstrated that
posttraumatic changes, mesial tempo- more sophisticated methods of image
ral sclerosis, and malformations of corti- reconstruction from 3-D acquisitions
cal development.40Y43 allow a better evaluation of patients with
The optimal MRI technique in adult discrete structural lesions (eg, focal
patients with focal seizures includes use cortical dysplasia) (Figure 1-8).40Y43
of a 3-tesla study in the coronal or
oblique-coronal, axial, and sagittal planes CONCLUSION
using T1-weighted, T2-weighted, and Epilepsy is a clinical diagnosis that is
fluid-attenuated inversion recovery often based on medical history alone as
(FLAIR) sequences. MRI epilepsy proto- health care providers rarely personally
cols should include a three-dimensional observe the patients seizure activity.
(3-D) T1-weighted volumetric acquisi- EEG is the most important diagnostic
tion with isotropic voxel size of 1 mm or tool that may assist in diagnosis, seizure
1.5 mm to enable the reconstruction classification, and monitoring response
of images in any plane.38Y41 FLAIR to treatment. Importantly, individuals
imaging sequences have shown an with normal routine EEG recordings
accuracy of 97% for detecting abnor- and recurrent seizures may be appro-
malities associated with mesial temporal priate candidates for AED therapy.

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Diagnosis of Epilepsy

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