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Epilepsies of infancy and childhood.

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NEUROLOGICAL PROGRESS
Epilepsies of Infancy and Chddhood
Manuel R. Gomez, MD, and Donald W. Klass, MD
This review deals with selected forms of epilepsy beginning after the neonatal period, with special emphasis on those
that are highly age dependent for their expression. Experience accumulated in the past decade provides helpful data
concerning the clinical-electroencephalographiccorrelations, remission rate, differential response to medications, and
prognosis, although many questions remain unanswered.
Gomez MR, Klass DW: Epilepsies of infancy and childhood. Ann Neurol 13:113-124, 1983
The annual incidence in the United States of patients
with seizures during the decade 1970-80 has been estimated as 21,070 in the age group 0 to 4 years, 11,900
in the age group 5 to 9 years, and 11,690 in the group
10 to 14 years 1331. The age-specific incidence rates for
epilepsy are highest in the first year of life and decrease
with succeeding decades until a secondary increase occurs after age 60 f551. This review deals with epileptic
seizures that occur in infancy and childhood. Seizures
in the newborn have been discussed in a previous review [57).
In recent years, efforts have been made to standardize the classification of epileptic seizures and the
epilepsies. The clinical and electroencephalographic
(EEG) classification of epileptic seizures (partial seizures or seizures beginning locally; generalized seizures
without local onset; unilateral or predominantly unilateral) drawn up by the International League Against
Epilepsy 1371 has gained wide acceptance, although a
modification of the classification has recently been proposed 1231. A classification of the epilepsies into generalized (primary, secondary) and partial types has also
been developed [SS]. The proportion of classifiable
cases in children under 15 years of age, although less
than that in adults [41), has been reported to be as high
as 71.895 131. Further refinements of these still controversial classification systems are needed in order to
compare data from different localities and improve
communication.
Influence of Maturation
The incidence of different types of seizures varies at
different ages. Furthermore, their clinical and electrographic expressions depend to a great extent on the
concurrent stage of maturation of the central nervous
system 121, 102-1041. Servit ills, 1161 has shown
that the stereotyped generalized tonic-clonic seizure is
From the Sections of Pediatric Neurology and Electroencephalography, Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN.
not present phylogenetically below the level of amphibians. An analogous change occurs with ontogenetic
development in humans, and stereotyped generalized
tonic-clonic seizures are rare in early infancy.
The basic mechanisms responsible for the various
distinctive clinical and EEG syndromes in humans that
appear and evolve or disappear with relatively specific
temporal patterns in childhood are only poorly understood. Large-scale studies by the Gibbses 1501 clearly
established the age profiles of epileptiform EEG patterns, and Kellaway 169, 70) has recently shed new
light on the relationship of age-specific epileptiform
EEG patterns to clinical seizures in children.
Of the two main classes of seizures, generalized and
partial, we will discuss only the most frequent types
found in infants and children and the syndromes in
which they are recognized.
Infantile Spasms
Kellaway et al [71), in monitoring a large number of
infantile spasms with EEG, electromyography, electrocardiography, accelerometry, and video recordings,
showed that infantile spasms consist of a brief initial
phase with rapid contraction of neck, trunk, and bilateral limb muscles, followed by a tonic phase of
sustained contraction usually lasting 2 to 10 seconds.
The initial phase may involve flexion, extension, or
mixed flexion-extension of different muscle groups.
Approximately one-third of infantile spasms are purely
flexor, 22% are extensor, and 42% are mixed flexorextensor 171). In the mixed variety, flexion of the neck,
trunk, and arms is accompanied by extension of the
legs; or flexion of the neck, trunk, and legs is accompanied by extension of the arms. Infantile spasms can
be so subtle as to be easily overlooked 1711. They
usually cluster in groups, are more apt to occur during
the waking state than during sleep, and are particularly
Received Apr 28, 1982, and in revised form July 26. Accepted for
publication Aug 1, 1982.
Address reprint requests to Dr Gomez, Mayo Clinic, 200 First St
SW, Rochester, M N 55905.
0364-5134/83/020113-12$1.50 0 1982 by the American Neurological Association
113
prone to occur as the patient awakens. Occasionally,
they follow a startling stimulus. They may be preceded
by irritability, accompanied by a smile or grimace, and
followed by placid calm, crying, or laughter. Crying
may be interrupted by an attack but rarely occurs during it.
The onset of infantile spasms is before 1 year of age
in 86% of patients. The peak age is between 3 and 8
months [65]. Such patients may have additional seizures, most commonly myoclonic, tonic, or tonicclonic in type. Psychomotor development may have
been delayed before the onset of the infantile spasms,
but more often the retardation is noted after their onset.
The interictal EEG recording of patients with infantile spasms is almost always severely abnormal and typically demonstrates the constellation of abnormalities
known as hypsarrhythmia [49]. This pattern rarely persists beyond the age of 4 or 5 years. During the seizure,
the EEG characteristically shows an abrupt diffuse electrodecremental pattern [ 131, which is often heralded
by a bisynchronous slow-wave or spike-and-wave complex.
The association of infantile spasms, arrest of psychomotor development, and hypsarrhythmia has been
called the West syndrome {39]. An etiological
classification of this syndrome IS shown in Table 1.
The cause is unknown in about 40% of patients {92].
Preceding ischemic-hypoxic encephalopathy is a frequent perinatal event, and congenital infections, cerebral defects of development, metabolic encephalopathies, and tuberous sclerosis are the most common
prenatal causes. Among postnatal causes are craniocerebral injuries, central nervous system infections,
postinfectious and postimmunization encephalopathies, hypoglycemia, and pyridoxine deficiency. In
the 200 patients reported upon by Matsumoto and
associates {85}, the presumed cause was prenatal in
36.5%, perinatal in 2296, postnatal in 8.596, cryptogenic in 9%, and doubtful in 24%. The diversity of
causes suggests that the syndrome represents a response of the immature brain to cerebral insult at a
particular stage of development.
Since the introduction of computed tomography
(CT), structural lesions associated with the West syndrome have been recognized at an early age in many
patients, a large percentage of whom have anomalies of
development such as agenesis of the corpus callosum
with or without associated cerebral atrophy, subependymal nodular calcifications characteristic of tuberous
sclerosis, and porencephaly. Among 37 patients reported by Gastaut and colleagues [42],only 7 had normal CT scans.
In considering treatment of infantile spasms, a search
should be made for potentially reversible causes. However, only some metabolic diseases, such as phenyl-
114 Annals of Neurology VoI 13 No 2 February 1983
Table 1. Some Presumed Causes of West Syndrome
Metabolic abnormalities
Phen ylketonuria
Maple syrup urine disease
Hyperornithinemia
Isovaleric acidemia
Nonketotic hyperglycinemia
Pyridoxine dependency
Leucine-sensitive hypoglycemia
Tay-Sachs disease
Dysplastic or dysgenetic conditions
Tuberous sclerosis
Microgyria
Ulegyria
Down syndrome
Sturge-Weber angiomatosis
Agenesis of corpus callosum
Aicardi syndrome
Schizencephaly
Lissencephaly
Porencephaly
Linear nevus sebaceous syndrome
Prenatal infections
Cytomegalovirus
Syphilis
Toxoplasmosis
Perinatally or postnatally acquired encephalopathiej
Ischemic-hypoxic
Hypoglycemic
Traumatic
Infectious
Encephalitis
Complicated meningitis
Postexanthematous diseases
Postimmunization (pertussis, influenza)
lntracranial tumors
Choroid plexus papilloma and others
Unknown
ketonuria, maple syrup urine disease, isovaleric
acidemia, pyridoxine dependency, hypoglycemia of
various causes, certain central nervous system infections, and subdural hematomas, can be treated directly.
Symptomatic treatment with adrenocorticotropic
hormone (ACTH) or adrenocorticosteroids is recommended for most patients with the West syndrome.
The recommended intramuscular dose of ACTH
varies between 4 0 and 120 U daily for two to four
weeks. In a recently published study 11IS}, 40 U given
daily for two weeks was followed by alternate-day
therapy with 80 U for three months. An excellent response was obtained: 87% of patients who had infantile spasms for less than 1 month and 38% of those
who had had spasms for more than one month became
seizure free. Relapse occurred in 3.796 of the first
group and 21.4% of the second. Hormonal treatment
may decrease the seizures and EEG abnormalities regardless of cause. Unfortunately, mental and motor dis-
abilities do not always improve when infantile spasms
stop.
ACTH is more effective than corticosteroids €or the
treatment of patients with infantile spasms C741. In a
comparative study, ACTH controlled seizures in
100% of patients within five days, whereas prednisone
was effective in only 60% of patients within fourteen
days I1 171. In another study, cessation of seizures and
normalization of the EEG occurred in 4 of 5 patients
who received low-dose ACTH therapy compared with
3 of 12 who were treated with prednisone [62, 631.
Nitrazepam, clonazepam, barbiturates, or a ketogenic
diet can be used when ACTH or corticosteroids fail.
Recently, 40%’ of a group of patients with infantile
spasms had a beneficial response to valproic acid; side
effects were less prominent than with hormonal
therapy 18).
TI-ere is a great discrepancy in the reported results
of hormonal therapy for infantile spasm5 C751. The prevailing view, although not documentrtd by an adequately designed study, is that the earlier treatment is
instituted, the better the chance of a complete remission. O n the basis of this assumption, the patient
should be treated before one month has elapsed after
the onset of infantile spasms. Patients with cryptogenic
infantile spasms have remissions more often and relapses less frequently than those with demonstrable associated disorders [651. The relapse rate for all ACTHtreated patients is about 50%. A second course of
treatment is then indicated, but the probability of a
good response is less with the second than with the first
attempt C75). If seizures recur, this is most likely to
take place within two months after completion of the
hormonal treatment.
Behavioral changes are often noted as the infantile
spasms decrease in frequency: the infant becomes irritable and sleepless. These effects subside as the daily
dose of ACTH is diminished. Additional side effects
are obesity with cushingoid appearance, acneiform skin
eruption, arterial hypertension, hypotension, congestive heart failure, and delay of growth in height. Dilatation of the subarachnoid spaces and ventricles resembling cerebral atrophy, as demonstrated by CT of the
head, has been reported after steroid therapy 1541.
Ideally, effective treatment of West syndrome would
prevent progressive psychomotor deterioration, but no
controlled studies with long-term follow-up examinations have been done to compare treated with untreated infants. A retrospective study C1201 indicated
that at follow-up, a greater percentage of hydrocortisone-treated than untreated patients were of normal
intelligence.
The long-term prognosis of the West syndrome is
related to (1) the nature of the associated etiological
disorders, (2) the state of mental and neurological development before onset of the seizures, and (3) the
cessation or persistence of the infantile spasms. In a
report of 150 patients 1661, 37% of the cryptogenic
and postimmunization groups with previously normal
development had complete recovery, whereas of the
total number of patients only 16% recovered, 345%
were subnormal, 47% had other neurological deficits,
and 22% died. In a previous report from the same
authors C671, 15 of 22 untreated patients stopped having spasms before the age of 4 years and only 14 of 98
treated and untreated children were attending school
for normal children. Ten attended school for the subnormal, 18 were in a training center, 38 were severely
mentally retarded, and 18 had died. The patients with
cryptogenic seizures did better than the rest. Matsumoto et al 1851 concur with the better prognosis in
cryptogenic cases (normal mental and physical development in 44%).
Although it is reasonable to suppose that the same
process that causes the infantile spasms also leads to
delay or arrest of psychomotor development and mental subnormality, the spasms seem to constitute an indicator of the degree of success treatment may have on
the entire syndrome. When the seizures stop, patients
become more alert and start to make progress again,
even if congenital structural lesions of the brain are
present [52]. However, in one follow-up study, only
22% of children who had shown a good response to
ACTH therapy (cessation of seizures for at least three
weeks and disappearance of hypsarrhythmia) were seizure free and without mental impairment 11011.
Generalized Epileptic Seizures of Childhood
Toward the end of the first year of life and continuing
throughout childhood, a large group of seizures occur
which are primarily generalized from onset. These include myoclonic, tonic, atonic, tonic-clonic, and absence seizures {30]. Although the ictal EEG manifestations vary with different types of attacks, the
electrographic manifestations are bilaterally synchronous at onset. For many of these seizures, the cause
remains unknown even after extensive investigation.
Some, however, may be caused by diseases with a wide
spectrum of severity. Prognosis depends not only on
the type of clinical seizures and ictal EEG pattern but
also on the interictal state of neurological and electrical
function and other diagnostic tests.
The Lennox-Gastaut Syndrome
The association of the EEG pattern of “petit mal variant” 148) or “slow spike-wave” {78}with certain clinical
aspects led to the concept of a syndrome variously
named “severe myokinetic epilepsy of early childhood
with slow spike and wave” [122}, “childhood epileptic
encephalopathy with diffuse slow spike-waves” C451,
“Lennox syndrome” I1 131, and, later, “Lennox-Gastaut
syndrome” 138, 761. It is characterized by onset of
Neurological Progress: Gomez and Klass: Epilepsies of Infancy and Childhood
115
seizures early in childhood. More than one variety of
generalized seizures occurs, predominantly tonic, tonic-clonic, atonic, akinetic, absence, and myoclonic
117, 22, 1131; mental retardation is often present, and
refractoriness to the common anticonvulsant drugs is
the rule. The EEG contains generalized sharp- and
slow-wave complexes 117, 22, 45, 84, 1131.
The maximal age expression of the Lennox-Gastaut
syndrome is between 1 and 5 years, with a slight preponderance of males 117, 22, 30, 84, 1141. Some affected patients have previously had infantile spasms
and may continue to experience these as they acquire
other types of seizures. Seizures are the first symptom
of the Lennox-Gastaut syndrome in the majority of
patients, with an age at onset varying from 1 day to 17
years and a mean age of 26 months 117, 22). During
“minor” status epilepticus (prolonged episodes of frequently repeated akinetic or myoclonic seizures) the
patient may be unable to maintain the head erect. The
accompanying difficulty in eating and swallowing resembles pseudobulbar palsy C301.
Delayed psychomotor development is found in 20 to
30% of patients when they present with seizures [17,
22, 301. Additional abnormalities in the neurological
or ophthalmological examination are found in 30 to
59% of patients C17, 841. Mental subnormality is recognized in 90% of patients by the time they are 5 Y 2
years old E22). In one study, the mean age at seizure
onset was 30 months among patients with subnormal
intelligence and 7 years 2 months among subjects with
normal mentality at follow-up 1171. Mental deficit is
especially prevalent in patients who have had infantile
spasms, tonic seizures, or minor status epilepticus 117,
301.
Radiographic investigations have demonstrated examples of generalized cerebral atrophy 130, 1131.
Other radiographic findings include cerebral malformation, unilateral or localized cerebral atrophy, and intracranial calcification in toxoplasma and cytomegalovirus
infections and in tuberous sclerosis.
The etiological factors responsible for the LennoxGastaut syndrome are numerous and overlap with
those of the West syndrome (Table 2). Prenatal events
have been suspected in 10 to 15% of cases C74, 84,
113}, perinatal factors invoked in 15 to 36% [45, 74,
84, 1131, and postnatal causes found in 0 to 25% 184,
1131 in different reported series. The cause was unknown in 30 to 70% C74, 84, 1131, but delayed
psychomotor development in many of these children
supports the impression of a preexistent cerebral abnormality. Once the syndrome has become established,
the underlying causes are usually not treatable, although some are preventable. Rarely, the syndrome
represents secondary generalization from a focal lesion
that is amenable to surgical treatment 16, 611.
The seizures in these patients are notoriously
116 Annals of Neurology
Vol 13 No 2
February 1983
Table 2.Causes of Lennox-Gastaut Syndrome
Metabolic abnormalities
Phen ylketonuria
Lipidosis (GM,, GM3)
Metachromatic leukodystrophy
Ceroid lipofuscinosis
Homoc ystinuria
Hypoglycemia of various causes
Dysplastic or dysgenetic conditionj
Tuberous sclerosis
Encephalofacial angiomatosis
(Sturge-Weber syndrome)
Megalencephaly
Other cerebral malformations
Perinatal events
Ischemic-hypoxic encephalopathy
Intracranial hemorrhage
Hyperbilirubinemia
Postnatally acquired disordeu
Purulent meningitis
Cerebral venous thrombosis
Acute encephalitis
Postinfection encephalopathy
Postimmunization encephalopathy
Craniocerebral trauma
Cerebral hypoxia
Stroke (acute hemiplegia)
encephalopathy
Intracranial tumors
Unknown
difficult to control with anticonvulsant drugs. Anticonvulsants commonly used for generalized tonic-clonic
seizures, such as phenobarbital and phenytoin, are
usually ineffective. Barbiturates often induce hyperactivity. Nitrazepam, clonazepam, and other benzodiazepine derivatives, given orally, may succeed in
reducing the frequency of myoclonic seizures, although
diazepam is ineffective in abolishing the interictal EEG
spike- and slow-wave complexes 1841. Moreover, in
some instances, diazepam administered intravenously
has resulted in increased tonic seizures and tonic status
epilepticus with ictal apnea 114, 1241. Ethoswimide
and acetazolamide have sometimes proven beneficial
when other anticonvulsants have failed. Valproic acid
or sodium valproate has been more successful in our
experience than any of the other anticonvulsant drugs
in patients with akinetic or tonic seizures, whereas
clonazepam is more often effective for myoclonic seizures 153, 1111. Unfortunately, up to 25% of patients
who respond to clonazepam become resistant after taking it for a few months 1191. Valproate may be used in
combination with clonazepam for patients who have
both akinetic and myoclonic seizures.
ACTH has been used to treat the Lennox-Gastaut
syndrome, although the reduction of seizures has been
said to be transient 122, 45, 122). According to a re-
cent report, daily intramuscular injections of ACTH
brought some improvement to 9096, and seizures
stopped completely in about 70% of patients within
two weeks after initiation of treatment f127f. Of these
patients, 2 1% remained seizure free during a follow-up
period lasting between one and fourteen years, 43%
relapsed within six months, and 34% relapsed at a later
date. The dose given was 10 IU (0.25 mg) for infants
and 30 IU (0.75 mg) for older children. The duration
of therapy varied between 10 and 57 days. Relapse may
be prevented by using a larger initial daily dose (e.g.,
40 IU for children) and tapering it gradually over a
period of many months or as long as a year 1971. Treatment with ACTH is more often successful in patients
younger than 4 years, in patients whose seizures have
been present less than one year, in cryptogenic cases,
and in patients with tuberous sclerosis when treated
early 11271.
For about fifty years the ketogenic diet has been
used to treat patients who have generalized seizures
that do not respond to anticonvulsant medications
[687. The seizures of patients with the Lennox-Gastaut
syndrome sometimes improve substantially after institution of “the lardaceous hegemony” 1991. Failure of
the ketogenic diet is often due to inability to maintain
the patient in ketosis with a strict diet. The difficulty
may be lessened by substituting the more palatable
medium-chain triglycerides (MCT oil) for the abundant
fatty foods of the natural ketogenic diet 1641.
Long-term follow-up studies have shown that regardless of the type of treatment used, the proportion of
patients whose seizures stop is greater for those whose
onset of seizures was in late childhood than for those
with seizure onset in the first two years of life 1171. The
prognosis for cessation of seizures is worst for patients
with tonic seizures, infantile spasms, and minor status
epilepticus 117, 30). The proportion of the EEG which
is occupied by slow and spike waves on the initial recording has no prognostic value for future control of
seizures or mental development 1171. Prompt cessation
of seizures after treatment augurs a good prognosis.
Generalized Tonic-Clonic Seizures
The generalized tonic-clonic seizure (grand mal), the
most common epileptic symptom of children 1977, can
occur as the only type of seizure, in combination with
generalized seizures of other types, or as secondary
generalization of a partial seizure. During the attack,
the EEG first shows generalized repetitive spikes during the tonic phase and then periodic bursts of spikes
during the clonic phase, although the surface recording
is contaminated by muscle artifact. Immediately after
the seizure, there is transient attenuation of electrical
activity followed by generalized slow waves.
The onset of generalized convulsive seizures may
occur at any age except in neonatal life. There is often a
family history of seizures. Some patients have a past
history of febrile convulsions. If there is no other sign
of neurological disease, the seizures can usually be controlled with anticonvulsants such as phenobarbital,
phenytoin, carbamazepine, or valproic acid. The choice
of anticonvulsant for treatment of generalized tonicclonic seizures associated with other types of seizures
depends on whether the other types are generalized or
partial.
Absence (Petit Mali Seizures
The concept of absence seizures has undergone considerable modification in the last twenty years. NO longer
are the clinical manifestations considered to be invariably simple (brief spells of unresponsiveness with arrest
of movement or rhythmic movements of the eyelids).
Close observation aided by simultaneous recording of
the patient and the EEG on movie film or videotape
has demonstrated much clinical variation C72, 1007
among attacks in different patients and in different
attacks in the same patient 130, 72, 1001. The EEG
provides an accurate index of these seizures since a
paroxysm of generalized 3 Hz spike- and slow-wave
complexes invariably occurs with each attack. This feature is important from a diagnostic standpoint because
automatisms resembling complex partial seizures can
occur in a large fraction of these patients [loo}. Only
40% of patients in one study [lo01 had one or more
simple absences during prolonged periods of observation, and only 9% of the total number of seizures recorded were simple absences. Other possible associated clinical features of absence seizures include
myoclonus, increased postural tone, version of the
head and conjugate deviation of the eyes, decreased
postural tone, and autonomic changes. In the past, approximately 50% of patients with absence seizures also
experienced generalized tonic-clonic seizures 147, 837,
although this proportion may be decreasing as a result
of more effective treatment.
Absence seizures usually last less than 10 seconds,
but exceptionally an attack may last nearly a minute.
Absence status, however, may last for hours, with
clouding of consciousness and reduced accuracy of responses but without noticeable abrupt interruptions. In
children it has sometimes been misinterpreted as a
nonictal behavior disorder, toxic confusional state, or
mental retardation. This form of status does not appear
to have any deleterious prognostic implication [57, and
the status can usually be quickly terminated by intravenous administration of diazepam I l O S } .
Maturation plays an important role in the expression
of these seizures. The onset of absences is rare before
the age of 3 years, most common between 4 and 11
years of age, and unusual after age 20 years.
The observations that monozygotic twins are 84%
concordant for spike-and-wave discharges at 3 Hz and
Neurological Progress: Gomez and Klass: Epilepsies of Infancy and Childhood
117
75% concordant for petit mal seizures, whereas dizygotic twins are discordant [77), indicated a hereditary
factor in this disorder. The Metrakoses [89-91) have
suggested an autosomal dominant mode of inheritance
for the spike-and-wave EEG trait with age-dependent
expressivity. These authors found the spike-and-wave
pattern in recordings from 35% of siblings and offspring of probands with “spike-wave epilepsy,” a proportion that was much higher than in comparable relatives of a control group. In the same studies, the
prevalence of seizures was four times higher in close
relatives of the probands compared with the controls.
Doose et alC291, however, have postulated polygenetic
factors for absences with spike-and-wave discharges. A
genetic influence also has been implicated for other
types of seizures C4, 18, 77, 951.
The two most effective drugs for the treatment of
absence seizures are ethoswimide and valproate.
Ethosuximide is relatively free of undesirable side effects or serious complications and is more economical
than valproate. Because of the risk of generalized
tonic-clonic seizures, a second anticonvulsant drug such
as phenobarbital is often necessary. Valproate given
alone {117) not only is effective in controlling absences
but also prevents major generalized seizures; however,
uncommon but serious idiosyncratic reactions with
hepatocellular damage [43] can occur.
Clonazepam may control absence seizures, particularly attacks with associated myoclonus, but it does not
prevent tonic-clonic seizures. A frequent disadvantage
is the tendency for clonazepam’s effectiveness to decrease with continued use. Acetazolamide has sometimes proved to be effective alone or in combination
with ethoswimide. The ketogenic diet with natural fats
or with artificial medium-chain triglycerides is now
generally used only when anticonvulsant drugs fail or
produce untoward reactions. It is customary to treat
patients with absence seizures until they have been seizure free for at least two years and the EEG no longer
shows spike-and-wave discharges.
The prognosis for remission of absence seizures has
been a controversial subject, apparently because of differences in the selection of patients studied and duration of follow-up. In general, the remission rate is
greater for simple absences not accompanied by other
seizure types, but actual rates have varied considerably
in different series [l09]. In a long-term follow-up
study of 117 patients [791,92 (78.6%) were in remission, and 89 of these patients were 20 years of age or
younger when they became seizure free. In another
study with average follow-up to age 25 years [25}, 56%
of the patients continued to have seizures; 37% had
acquired “grand mal” seizures, but none after the age of
18 years; for “petit mal” seizures, the average age at
onset was 7 years and the average age at cessation was
14 years. In a study of 213 patients [llo], the prog-
118 Annals of Neurology
Vol 13 No 2 February 1983
nosis for remission of seizures was favorable when the
onset was between 5 and 9 years of age, absence seizures were unassociated with other types of seizures,
and intelligence was normal.
In a longitudinal study of patients with epilepsy [71,
the probability of remission (at least five years seizure
free) at twenty years after diagnosis was 80% for patients with absence seizures (with or without generalized tonic-clonic seizures), 85% for those with generalized tonic-clonic seizures, and 65% for those with
complex partial scmres. Another longitudinal study
11211 followed 511 epileptic children for four to ten
years and determined a two-year remission rate of 7 8%
for simple absence seizures, 72% for “grand mal” seizures, 64% for elementary partial seizures, and 36%
for complex partial seizures.
Partial Seizures
Partial seizures can be classified into two types [23]: (1)
those with elementary symptomatology (or simple), in
which there is no impairment of consciousness, and (2)
those with complex symptomatology (or complex), in
which there is some impairment of consciousness. Simple partial seizures are subdivided according to manifestations as motor, sensory (somatosensory or special
sensory), autonomic, psychic, and compound (mixed).
The complex partial seizures are associated with impaired consciousness at onset, or they begin as a simple
partial seizure and are followed by impaired consciousness. Both simple and complex partial seizures
may progress to a generalized tonic-clonic seizure.
Simple Partial Seizwes
The simple partial seizures are more common in infancy than in childhood. In children they are often
followed by rapid generalization so that the focal onset
may not be recognized. Young children cannot give a
good account of the initial sensory or autonomic symptoms, and parents seldom make accurate observations of early motor manifestations. Nevertheless, the
neurological examination in the interictal state or the
EEG may demonstrate a focal abnormality. Distinctively epileptiform EEG abnormalities may appear only
during sleep. CT scan of the head has been reported to
be abnormal in 63% of patients with partial seizures
C40, 1141, with focal abnormalities in 78% and diffuse
ones in 22% {98}. The most effective drugs for treating partial seizures are carbamazepine, phenytoin,
phenobarbital, and primidone.
BENIGN FOCAL EPILEPSY.
This electroclinical syndrome [9, 28, 931, variously called “benign focal
epilepsy of childhood” [97],“benign epilepsy of children with centrotemporal EEG spikes” C161, “Sylvian
seizures and midtemporal spike foci” [811, and “benign
childhood epilepsy with Rolandic paroxysmal dis-
charges” [SO}, consists of a constellation of specific clinical and electrographic manifestations, characteristic
ages at onset, and usually benign outcome. Its onset is
without any immediately preceding illness, usually occurs between 4 and 10 years of age, and is more common in boys than in girls. An adversive or a generalized
seizure during sleep in the early hours of the morning
or on awakening is often the first symptom. In about
half the cases, seizures occur only during sleep I1 1,
121. When they occur during waking, the initial symptom is sensory or motor, involving one side of the
tongue, mouth, and face accompanied by salivation and
gurgling sounds. The patient is unable to speak or swallow and yet is fully conscious. The speech arrest is due
to anarthria [8l}. The symptoms correspond to a probable origin from the inferior rolandic cortex near the
sylvian fissure 181). The sensory involvement is usually
contralateral to the focal EEG sharp waves, but it may
be ipsilateral. Rarely, a typical jacksonian march occurs
1811. During sleep, the focal motor manifestations usually do not awaken the patient and are detected only
when the patient is under continuous close observation
I261.
A genetic factor appears important. In one study, a
history of seizures was obtained in 18% of parents and
siblings of patients with benign focal epilepsy and centrotemporal EEG foci {lb}. In another report, 17 of 26
patients with rolandic spikes also had generalized 3 to 4
Hz spike-and-wave discharges [lo].
The incidence of benign focal epilepsy found in one
study [56] was 21 per 100,000, or about 16% of all
afebrile epileptic seizures with onset below 15 years of
age, and more than four times as frequent as “petit mal”
epilepsy. The natural history of benign focal epilepsy
based on a prospective study of 58 consecutive patients
{Sl} showed that within five years, 75% of patients
were seizure free and 60% had a normal EEG.
The effectiveness of treatment with anticonvulsant
medications in this syndrome is difficult to assess. In a
study of 324 patients with follow-up of between one
and twenty-two years 1127, those who received regular
treatment for more than five years showed no better
remission at the end of therapy than patients receiving
treatment for only one year. Seven of 21 patients who
received no treatment and were followed more than
two years had only one seizure. There appears to be a
trend toward remission of seizures with or without
treatment.
Caution should be exercised about considering this
syndrome a discrete entity. Few reports have described
the location of the EEG spikes as precisely as the topography so well documented by Lombroso [Sl}. The
location has encompassed areas referred to as rolandic,
centrotemporal, posterior-frontal, central, midtemporal, sylvian, and parietal {12, 16, 56, 80, Sl}. Blom
and Brorson [l51 found that neurological abnor-
malities, particularly those classified as “cerebral palsy,”
were frequent in children with rolandic spikes. Others
in reviewing the syndrome have specifically excluded
patients with interictal neuropsychiatric abnormalities
I l l ] or the “possibility of encephalopathy” [lZl.
It is appropriate to recall that symptoms in a child
whose EEG shows a central spike focus are not necessarily epileptic seizures [46]. Kellaway [67} found that
only 38% of 638 children with central spike foci had
clinical seizures.
APHASIA ASSOCIATED WITH EPILElTIFORM ACTIVITY IN
The first report of this unusual syndrome
[76} described 6 children with acquired temporary
aphasia lasting days to months, associated with seizures
and generalized spike-and-wave discharges in the EEG,
whose language disorder and EEG abnormalities improved together. Since then, more than 40 similar patients have been reported [36, 58, 82, 87, 105, 112,
1261, but not all suffered isolated aphasia as had been
first described.
The language disturbance in the “epileptic aphasia
syndrome” category is not the result of a gross focal
cerebral lesion, and it is not an ictal or postictal phenomenon. The seizures may be simple partial, complex
partial, generalized conic-clonic, absence, or akinetic,
or there may be no seizures at all. The onset of symptoms is either gradual or abrupt and occurs between 3
and 9 years of age. The aphasia fluctuates and does not
necessarily coincide with the recurrence of seizures. A
behavior disorder may be associated, but intelligence
appears to be unaffected. The reported paroxysmal
EEG abnormalities vary: bilateral independent temporal or temporoparietal spikes, bilateral 1 to 3 Hz spikeand-wave activity maximal over temporal regions, generalized sharp waves or spike-and-wave discharges,
multifocal spikes, or unilateral spikes. The long-term
prognosis varies between complete recovery and permanent language impairment.
A recent study of 2 patients 1581 with EEG telemetry and video-audio monitoring during speech and
language examination failed to demonstrate a correlation between the speech abnormalities and the epileptiform activity in the EEG. The authors proposed that
“the EEG abnormality in this syndrome is an
epiphenomenon of underlying pathology of brain areas
concerned with speech rather than a cause of the
speech abnormality.”
THE EEG.
Most partial seizures are brief, stereotyped, and sporadic in occurrence. A less common variety consists of persistence of
the clonic muscular twitches of one part of the body for
hours, days, months, or years [125]. Twitching may
vary in rate, rhythm, and intensity and affect closely
related muscle groups asynchronously. The distal porEPILEPSIA PARTIALIS CONTINUA.
Neurological Progress: Gomez and Klass: Epilepsies of Infancy and Childhood
119
tion of the upper extremity is affected more often than
the proximal part. Trunk muscles are rarely affected. In
a study of 32 patients of all ages 11251, the duration of
epilepsia partialis continua (EPC) ranged from four
hours to eighteen years with a mean of twenty-five
months. The EEG usually shows a focal or lateralized
spike, sharp-wave, or slow-wave abnormality.
The causes of EPC are diverse and include cerebral
infarction, hemorrhage, neoplasm, trauma, and inflammation. In some patients no cause can be identified.
This disorder in children may be a manifestation of the
“Rasmussen syndrome” of focal epilepsy and progressive neurological deficits presumably due to a chronic
smoldering encephalitis El, 106, 1071. In this last syndrome, histopathological examination has shown inflammatory lesions, including perivascular infiltration
by lymphocytes and glial nodules. A viral cause has
been suspected, but no specific agent is yet identified.
No medical or surgical treatment has been effective in
arresting the course of this disease, although surgical
treatment can help control intractable seizures after
progression of the disease has stopped {l06}.
The motor manifestations of EPC have sometimes
been mistaken for nonepileptic movement disorders
such as chorea. However, focal epileptiform EEG discharges can firmly establish the epileptic mechanism in
the disorder.
Complex Partial Seizuyes
Complex partial seizures are less common in children
than in adults {241. They are usually recognized in the
latter half of the first decade of life and in adolescence,
paralleling the emergence in later childhood of the typical focal anterior temporal sharp wave in the interictal
EEG [SO]. Although these seizures arise most frequently from the temporal lobe, there is ample evidence that they can originate from other regions of the
brain 1731.
Stevens El231 pointed out the importance of distinguishing these partial seizures from “petit mal” attacks
for “delineation of cause, planning investigative procedures, and proper choice of treatment.” On the one
hand, brief complex partial seizures can consist simply
of arrest of movement with loss of consciousness and
resemble generalized nonconvulsive absence seizures.
On the other hand, absence seizures with automatisms
can exhibit manifestations usually associated with complex partial seizures [72, 1001. The ictal EEG distinguishes conclusively between the fundamentally different types of seizures {733.
Complex partial status epilepticus, a rare phenomenon in adults, has recently been reported in 4 children
aged 1 to 4 years [86]. Ictal manifestations included
impaired consciousness and decreased reaction to pain,
absence of vocalization, staring alternating with wandering eye movements or conjugate deviation of the
120 Annals of Neurology
Vol 13 No 2
February 1983
eyes, focal clonic movements, masticatory movements,
and automatisms. In each case the status was terminated by intravenous administration of anticonvulsant medication. Ictal and postictal EEGs helped distinguish this condition from absence status.
Presumptive causes of complex partial seizures in
children include perinatal complications, postnatal
head trauma, congenital malformations, cerebral inflammatory diseases, severe or prolonged seizures in
early life, and neoplasms (seldom). Often no definite
cause can be established. Complex partial seizures may
occur as a late aftermath of an acute hemispheric insult
with hemiconvulsions and hemiplegia in early childhood, the “HHE syndrome” 1441.
The ictal clinical manifestations of complex partial
seizures are legion {27). In children particularly, the
symptoms must be carefully distinguished from migrainous events 13l]. Olaser and Dixon [ S l) found that
the most common auras in children with complex partial seizures consisted of anxiety with visceral sensations, that younger children tended to have simpler
automatisms, and that interictal behavior disorders
were frequent.
In a report of 666 patients with complex partial seizures who were followed for an average of seven years,
the seizures began before the age of 15 years in 26%,
focal EEG abnormalities were present in 92%, and
“the duration of epilepsy before control of attacks was
independent of the age of onset” 1243.
Carbamazepine is the drug of first choice for children with complex partial seizures 1351. Phenytoin,
phenobarbital, primidone, or valproate may also be effective. In carefully selected patients with welllocalized incapacitating and drug-resistant seizures, surgical excision can offer substantial benefit.
Febrile Seizures
A convulsion that occurs in a child only during an acute
febrile illness is not necessarily indicative of epilepsy
but can represent an age-related benign disorder.
Nevertheless, in children with any of the epilepsies, a
generalized tonic-clonic convulsion may occur during
the course of a febrile illness. In other situations the
seizure and the fever could be caused by a central nervous system infection such as viral encephalitis, acute
purulent meningitis, iatrogenic hypernatremia, hyponatremia, or rapid intravenous administration of penicillin.
Children with febrile seizures often have a sibling or
parent with the same condition. The age at onset of the
first febrile seizure is generally between 6 months and
5 years. The febrile seizure is usually a generalized
tonic-clonic convulsion, but it may be purely tonic or
clonic or have a focal onset. Focal aspects and febrile
seizures of long duration (lasting more than 15 minutes
or occurring more than once in a 24-hour period) have
been termed “complex” 1941. Febrile seizures may recur with repeated febrile illnesses. Forty percent of
children who have had one febrile seizure experience a
second, almost always within one year.
Patients with an uncomplicated “pure” or “simple”
febrile seizure have a three-fold greater probability of
subsequent epilepsy (recurrent afebrile seizures) than
normal (15 per 1,000 versus 5 per 1,000)1941. Patients
whose first febrile seizure was “complex” have a probability of later epilepsy that is two to four times the
probability of patients with pure febrile seizures.
Preexisting neurological disease increases the risk of
subsequent afebrile seizures 1941.
The need for prophylactic treatment of febrile seizures has been a subject of controversy 1341. After a
child has had one such episode, prevention of recurrent
febrile seizures does not diminish the possibility of subsequent epilepsy. Anticonvulsants given orally at the
onset of fever do not reach therapeutic levels rapidly
enough to be effective in the acute situation. However,
recurrent febrile seizures are usually preventable with
daily oral administration of phenobarbital or sodium
valproate. Phenobarbital has the disadvantage of causing hyperactivity in about 40% of children who take it
regularly, and this symptom may be so disturbing in 10
to 20% E201 that the risk of recurrent febrile seizures
seems preferable to some parents. Carbamazepine is
ineffective in preventing febrile seizures in phenobarbital failures 1201. Sodium valproate carries a risk of
hepatic toxicity, and it must be given three times daily.
Thus, there are cogent arguments against prophylaxis
of febrile seizures with anticonvulsant drugs. On the
other hand, potentially serious complications of febrile
seizures, including respiratory embarrassment with resulting hypoxia during prolonged or severe convulsions
and true status epilepticus with its immediate dangers
and possible sequelae E23, also need to be considered
(see also 123a, 94a)).
The EEG is a useful adjunct for evaluating children
with febrile seizures. Although abnormal diffuse slowwave activity can be expected as a transient aftermath
of any generalized tonic-clonic seizure, the EEG returns to normal within a few days after an uncomplicated febrile seizure. After that time, diffuse slowwave abnormalities may persist if central nervous
system inflammatory disease or electrolyte or metabolic derangements are present; focal slow-wave abnormalities or lateralized attenuation points to intracranial
complications, and some paroxysmal abnormalities
indicate an increased risk for subsequent afebrile
seizures.
Prognosis after Withdrawal
of Anticonvulsant Medication
A more favorable outcome has been found for children
than for adults after drug withdrawal following pro-
longed control of seizures C591. Recently reported follow-up studies on children with diverse types of seizures have shown that 69 to 72% continued to be
seizure free 132, 60). Opinions differ concerning
significant predictors of outcome. One group of investigators [32] found that the most significant risk factors
for relapse were the number of seizures (more than 30)
before control was established and an abnormal EEG
when withdrawal was begun. In another study CbO],
risk of relapse was associated with long duration of
seizures (more than six years), neurological deficit, and
type of seizure (jacksonian or multiple). Both studies
132, 60) agreed that risks were not influenced by sex,
race, family history of epilepsy, or age at the time of
drug withdrawal.
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Announcement
Frank C . Zondlo, MD, working under the auspices of
the St. Paul-Ramsey Hospital Medical Education and
Research Foundation, is compiling a resource directory
for physicians with physical impairment. The purpose
is to list physicians with various physical disabilities
who are willing to provide information and referral
services to other physicians who incur similar disabilities and need specific information. Dr Zondlo estimates that 4% of all physicians are not in active practice because of a physically disabling condition, and that
one-quarter of these persons have the potential to be
rehabilitated into the active practice of medicine.
To date, the response to advertisements by D r
124 Annals of Neurology Vol 13 NO 2 February 1983
Zondlo has been disappointing, as the term, handicapped physician, used in the initial advertisements may
have been taken to imply disability for medical practice.
Physicians with any physical impairment, whether or
not they are handicapped in their practice, are urged to
contact D r Zondlo at 640 Jackson St, St. Paul, MN
5 5 101. Information forms will then be mailed. Copies
of the directory will be sent only to those physicians
who are listed therein and all correspondence is
confidential. Advice from a practicing physician with
even a minor physical impairment may be of benefit to
another physician with multiple impairments. The cornerstone of this project is your participation.
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