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8):1316, 2004
Blackwell Publishing, Inc.
C International League Against Epilepsy
Educational Lecture
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
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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
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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.
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