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Epilepsia, 45(Suppl.

8):1316, 2004
Blackwell Publishing, Inc.

C International League Against Epilepsy

Educational Lecture

Diagnosis and Treatment of Epilepsy


Hirokazu Oguni
Department of Pediatrics, Tokyo Womens Medical University, Tokyo, Japan

Summary: Purpose: The correct diagnosis of epilepsy leads to


an appropriate treatment.
Methods: The first step is to distinguish epileptic seizures from
nonepileptic attacks, and to make a precise seizure diagnosis and
classification. The next step is to identify the etiology or basic
disorders underlying the epilepsy by physical and neurologic
examinations, laboratory tests, including EEGs and neuroradiologic examinations. Although the EEG is the most important
laboratory examination for the diagnosis of epilepsy, limitations
of EEG interpretations must be recognized.
Results: A syndromic classification of the patients, to determine whether they fit known syndromes, should be attempted.

If patients do not match a described syndrome, a neurobiologic


approach, utilizing genetic, neurophysiological, and neuropharmacologic knowledge, alternatively provides useful information
to understand the neurobiologic background of epilepsy.
Conclusions: Both approaches have advantages and disadvantages for diagnosing and treating epilepsy. Both approaches
can be used interchangeably with patients with seizure disorders, depending upon their condition. The epilepsy diagnosis, etiology, and seizure-type diagnosis should be reevaluated
when seizure control is insufficient with first- and secondline antiepileptic drugs. Key Words: Diagnosis of epilepsy
Syndromic approachNeurobiologic approach.

Diagnosis and treatment of epilepsy cannot be separated; appropriate treatment can only be performed without a precise diagnosis of epilepsy. It is rare to observe a
seizure directly at the first medical examination or at an
outpatient clinic. Thus, the confirmation and diagnosis of
the seizure types usually rely heavily on the history taken
from the parents or caregivers. The first requirement is
to distinguish epileptic seizures from the nonepileptic attacks, such as syncopal attacks, atonic attacks caused by
moyamoya disease, and psychogenic seizures, etc. Syncope includes breath-holding spells in infancy, orthostatic
dysregulation during childhood, and a noxious vasovagal
reflex at any age. In distinguishing a syncopal attack from
an epileptic seizure, we must pay attention to the feeling of
blackouts or sensation of faintness immediately before
loss of consciousness and the presence of a provoking factor, such as standing for a long time, sudden unexpected
pain, or noxious stimuli. Next, we must ask the following questions directly to the patients or indirectly to the
parents to make a precise seizure diagnosis including the
aura content, clouded consciousness, understanding and
production of language during the seizure if the patient

is conscious (the involvement of a dominant hemisphere),


asymmetry of the seizures, presence of automatism, deviations of the eyes and head, and a dystonic arm posture.
The clinical manifestation of ictal automatism may differ among young children and older children or adults.
Young children may have an automatic seizure characterized by sudden rushing and holding their mother with
a fearful expression as if they were frightened of attack. After we confirm that the attacks are of epileptic
origin, we must ask the parents when the attacks most
often occur; during wakefulness, sleep, awakening, or
drowsiness. In idiopathic generalized epilepsy, generalized tonicclonic seizures (GTCSs) commonly occur during awakening or wakefulness, but during sleep or during
wakefulness and sleep in partial epilepsy or symptomatic
generalized epilepsy, respectively. We must ask carefully
about the provoking factors of the attacks. In idiopathic
generalized epilepsy, such as juvenile myoclonic epilepsy,
a lack of sleep provokes the attacks.
The next step is to identify the etiology or basic disorders underlying the epilepsy, so we ask about family
histories of convulsive disorders and neurological diseases. In Japan, a family history of involuntary movement,
late-onset dementia, or ataxia in adult relatives may suggest that children with intractable generalized epilepsy
with a slowly progressing clinical course will have

Address correspondence and reprint requests to Dr. H. Oguni at


Department of Pediatrics, Tokyo Womens Medical University, 8-1
Kawada-cho, Shinjuku-ku, Tokyo 162, Japan. E-mail: hoguni@ped.
twmu.ac.jp

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H. OGUNI

dentatorubral-pallidoluysian atrophy. Questions about the


history, including febrile convulsions during infancy, developmental delay, and central nervous system infection
should be asked. Physical and neurological examinations
should be performed carefully to identify the localization
and lateralization of minor neurological deficits. The dermatological findings should be carefully checked to rule
out the presence of a neurocutaneous syndrome.
Laboratory examinations should include blood sugar,
calcium, phosphorus, magnesium, creatine kinase, and
lactic acid, especially in children. In cases of intractable
epilepsy, CSF lactate, urinary organic and amino acids, or
other specific tests may be required.
The routine EEG should be recorded during wakefulness, sleep, photic stimulation, and hyperventilation. The
EEG is the most important laboratory examination for the
diagnosis of epilepsy, for the following reasons:
a. Electroencephalography is able to identify epileptiform EEG activity, supporting the diagnosis of
epilepsy. Also worthy of attention is localized slowwave activity, which may suggest an underlying cerebral abnormality.
b. The presence of a specific EEG pattern, such as 3-Hz
spikewave complexes or rolandic discharges, points
toward a specific epileptic syndrome and prognosis.
c. The localization and lateralization of the epileptogenic EEG foci can explain the clinical manifestation
of the aura and seizure manifestations of the patients.
In candidates for epilepsy surgery, the localization
and lateralization of epileptogenic foci should be
properly evaluated. EEG examinations, including
special EEG electrodes such as sphenoidal, zygomatic, and supraorbital electrodes should be considered.
In contrast, we also must know the limits for interpreting
the EEG findings for the following reasons:
d. The epileptiform EEG abnormality may not be identified in the first EEG examination. In addition, a few
patients do not show any epileptiform EEG abnormalities on repeated EEG examinations (1). In such
cases, we must make a diagnosis of epilepsy based
solely on the clinical history of the seizures.
e. The presence of an epileptiform EEG abnormality itself does not necessarily indicate the presence
of epileptic seizures. Genetically determined epileptic EEG abnormalities, including rolandic spike discharges, generalized fast or 3-Hz spikewave complexes and photosensitivity are incidentally identified
in children without seizure disorders. A family history of convulsive disorders in close relatives may
explain the presence of these epileptic EEG findings.
Epilepsia, Vol. 45, Suppl. 8, 2004

f. A localized epileptic EEG focus may shift in localization, become multifocal, or spread diffusely with
age in children with epilepsy (2).
g. The EEG may include both focal and generalized
epileptiform activity, which sometimes makes it difficult to classify epilepsy into either partial or generalized if the seizure type also is undetermined. One
of the examples is symptomatic partial epilepsy with
secondary bilateral synchrony, which is sometimes
encountered during childhood (3).
As a routine neuroimaging study for seizure disorders,
a head computed tomography (CT) scan gives us information about the structural abnormality of the brain. In
cases of symptomatic epilepsy, brain magnetic resonance
imaging (MRI) provides more detailed information than
does a CT scan. In patients with complex partial seizures,
brain MRI is especially useful to identify temporal lobe
abnormalities, because CT imaging is disturbed by temporal bone.
A neuropsychological examination also gives us information with regard to selective higher cognitive dysfunction in patients with localization-related epilepsy.
We must make a seizure-type diagnosis, then an
epilepsy diagnosis, and follow a treatment strategy based
on the analysis of the aforementioned information obtained on an outpatient basis. It is now more common for
epileptologists to take a syndromic approach, in which the
clinical and EEG characteristics, including the onset age,
seizure types, circadian rhythm of the seizures, and quality
of epileptic EEG abnormalities, are analyzed in detail (4).
Then we look for known syndromes sharing these features
of the patients. The advantage of syndromic classification
is to give us practically useful information regarding a
precise diagnostic, prognostic, and therapeutic approach
(5). However, not all patients fit into the described syndromes on an outpatient basis, although many epileptic
syndromes have been proposed. In addition, these syndromes vary in specificity from some that represent broad
concepts to others that are highly specific.
Conversely, a neurobiological approach, with genetic,
neurophysiologic, and neuropharmacological knowledge,
provides useful information to understand the neurobiological background of epilepsy that does not fit into
specific syndromes (5). Based on accumulated clinical
and experimental evidence, Gloor (6) proposed a concept of generalized cortico-reticular epilepsy. Idiopathic
epilepsy produced by genetically determined cortical hyperexcitability resided at one end of a spectrum, and
symptomatic epilepsy produced by acquired diffuse gray
matter pathology resided at the other end. Intermediate
cases were determined by mixtures of the genetic and acquired factors. Conversely, Doose (7) proposed a concept
of hereditary impairment of brain maturation, in which
he considers that genetically determined multifocal sharp

DIAGNOSIS AND TREATMENT OF EPILEPSY

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FIG. 1. Schematic drawing of the neurophysiologic mechanism underlying generalized spike-and-wave complexes. The
neurophysiologic mechanisms underlying
absence seizures and generalized spikeand-wave complexes based on various experimental studies (1014) are summarized and illustrated. This mechanism can
apply in part to that of spike-and-wave
complexes produced by the secondary bilateral synchrony (12) and of focal spikeand-wave complexes. The generalized
and focal spike-and-wave complexes have
been shown to give rise to atonic seizures,
epileptic-negative myoclonus, absence or
atypical absence seizures, and transient
interference with cognitive function. Ethosuximide is considered to suppress the
spike-and-wave complexes by blocking the
T-type calcium channel and thus abolishing the rhythmic sustaining mechanism
(14).

waves produce various clinical symptoms, and thus various epileptic syndromes, depending on the localization of
sharp waves in childhood partial epilepsy. These epileptic
syndromes, including benign epilepsy with centrotemporal spike foci, benign occipital epilepsy, LandauKleffner
syndrome, and epilepsy with continuous spikewaves during slow sleep, etc., are thus recognized as a clinical phenotype or clinical spectrum of this genetically determined
epilepsy with multifocal sharp waves. This conceptualization more easily can explain borderline cases. Atypical or
borderline cases are always identified, even in a discrete
epileptic syndrome with homogeneous clinical and EEG
characteristics. We should consider these atypical cases as
valuable examples giving us clues to the neurobiological
background of the syndrome itself, rather than excluding them from the syndrome as heterogeneous epilepsy
cases. If we do not, we may subdivide a small number of
patients into more and more subentities by rigid definitions, and this may be a never-ending story described by
Doose (8).
We have shown a dramatic effect of ethosuximide
(ESM) on children with atypical benign partial epilepsy, or
cryptogenic partial epilepsy with secondary bilateral synchrony first seen with partial seizures, epilepticnegative
myoclonus, and atypical absence seizures (9). The basic
neurophysiological mechanisms underlying spike-andwave discharges helps in part to explain how these seizures
are generated in the cortex and why they respond to ESM
(Fig. 1).
The neurobiological approach provides a global view
of the factors underlying epilepsy, but it does not provide
a precise diagnosis, prognosis, or therapeutic regimen, as
does the syndromic approach (5). Thus, both approaches
have advantages and disadvantages for ma king a diagnosis and treating epilepsy. At present, we should use both
approaches interchangeably with patients with seizure disorders, depending upon their condition.

Treatment decisions must consider recent advances in


first unprovoked seizure studies. The recurrence rate of a
first unprovoked seizure has been reported to range from
27 to 71%, depending on various factors (14). The recurrence rate reaches 30% in children with cryptogenic
generalized seizures when no EEG abnormality is present
(14). Antiepileptic drug (AED) treatment decisions should
be based upon the balance of risks and benefits of treatment, and the views of the patient or parents in the case of
a first seizure. A first-line AED should be prescribed for
patients based on the seizure type and syndromic classifications. The epilepsy diagnosis, etiology, and seizure-type
diagnosis should be reevaluated when seizure control is
insufficient with first- and second-line AEDs.
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