Intractable seizures associated with severe forms of
epilepsy have been shown to have serious consequences. Selected groups of
children with continued seizures will exhibit poorer developmental outcomes and
overall cognitive decline. This is perhaps best exemplified in children with
catastrophic epilepsy due to diffuse hemispheric disturbances. Epileptic
discharges from the abnormal hemisphere interfere with normal development in the
unaffected hemisphere and the frequent seizures in these children lead to an
overall developmental decline that in many cases will be irreversible (Figure
1).
Figure 1: T2-weighted coronal magnetic resonance imaging (MRI) scan of a
3-year-old child with right hemimegalencephaly and intractable seizures.
While
epilepsy has long been considered an ictal disorder,
the interictal effects of chronic epilepsy also warrant consideration. Affected
children must deal not only with continued seizures, but also with the side
effects of antiepileptic drugs, impaired social relationships, low self-esteem
and a loss of autonomy. Chronic seizures may result in the disruption
of the affected child's or teenager's education, socialization, employment
and family life. Also, patients with chronic epilepsy have a much higher
risk of injury when compared to the general population and the risk of sudden
unexpected death in epilepsy (SUDEP) has been estimated to be at least 24 times
higher than that in a general population. [3
]
Although most children with epilepsy will have a good overall prognosis,
there is a small but significant minority of patients who will either not
respond to antiepileptic drugs or will have a significant adverse reaction to
these medications. With the increased recognition of the morbidity associated
with intractable seizures and refinements in the evaluation and treatment of
these children, surgery is becoming a well-established part of the
treatment.
Non-invasive evaluation
Excluding lesional cases, to be considered for epilepsy surgery, a
patient must first be determined to be medically intractable. Different
definitions have been proposed, but all essentially require an inability to
achieve acceptable seizure control despite adequate drug trials. However, some
ambiguity remains because there has been no consensus as to what defines an
acceptable number of medications, or particular combinations of medications, or
the length of time a child must remain on a medication before being defined as
intractable.
Once a child's seizure disorder has been deemed
intractable, an extensive preoperative evaluation is undertaken in order to
classify the patient's epilepsy and to determine whether or not it can be
treated surgically. Questions that will need to be answered include the
lateralization of the ictal onset and localization of the specific area of
seizure onset. Additionally, it will also be necessary to determine if the area
of brain thought to be responsible can be removed without compromising important
functions such as movement, language, or memory.
The first phase of the evaluation of a child with epilepsy consists of a
thorough noninvasive workup. An extensive history with attention to both
antenatal and postnatal events is obtained as is a description of the semiology
of the ictal events in question. Of particular interest are the descriptions of
seizure onset and the physical manifestations that are present during the
seizure. A thorough neurological examination is also performed. Once this data
is obtained, then appropriate adjuvant testing is ordered and will generally
include neuroimaging and neurophysiological testing.
Despite significant advances in neuroimaging and neurophysiological
testing, no currently available imaging or electrophysiological modality can
accurately define the area of brain that is responsible for the seizures. For
this reason the preoperative evaluation will include a combination of testing
modalities to identify structural abnormalities, as well as areas of ictal and
interictal electroencephalogram (EEG) abnormalities.
Most patients being considered for epilepsy surgery will already have had
multiple interictal EEGs. While these studies are important in localization and
classification of the child's seizures, intensive video-electroencephalographic
(video-EEG) monitoring often provides more information. These tests are
conducted in an inpatient monitoring unit to allow for the reduction of the
patient's antiepileptic medications. In this setting, continuous EEG data is
collected and the patient's habitual seizures are correlated with behaviors
recorded on video and the EEG recordings. In many cases lateralization can be
determined and the seizure type can be properly classified.
Modern
neuroimaging techniques have significantly improved our ability to identify
focal and diffuse pathologies that can cause epilepsy. Magnetic resonance
imaging (MRI) and its application to clinical epilepsy has increased our
understanding of structure as it relates to various epileptic syndromes and has
become the imaging modality of choice in the investigation of patients with epilepsy.
MRI can diagnose neoplastic lesions and vascular malformations, as well
as structural abnormalities such as cortical dysplasias (Figure 2), neuronal
heterotopias and mesial-temporal sclerosis. [4,5
]
Figure 2: T2-weighted coronal MRI scan demonstrating an area of cortical
dysplasia within the inferolateral right frontal lobe. This area correlated with
the child's ictal and interictal electroencephalogram (EEG) studies that
suggested right frontal lobe epilepsy.
Most current MR imaging is performed in 1.5 Tesla units, but 3T MRI has
recently been approved by the Food and Drug Administration and these scanners
may increase our ability to detect lesions and define their character. The role
of functional MRI in localization of cerebral language and memory function is
still being defined.
When focal seizures become medically refractory, MRI may assist in
selecting surgical candidates and in guiding the surgical resection. When an
abnormality is detected, its location is usually interpreted in the context of
the available EEG and video-EEG data. Certain patients may be considered for
surgery at this point, if the imaging and EEG data are concordant. In more
complicated patients, other methods of localization are often necessary before
surgery can be recommended. Since epilepsy does not always correlate with an
anatomic substrate, functional imaging can be particularly useful. Positron
emission tomography (PET) provides information about the metabolic activity in
the brain and can assist in localization of a seizure focus. Flourodeoxyglucose
(FDG) is the most commonly used tracer in the presurgical evaluation of epilepsy
patients. FDG is taken up by neurons and glia in proportion to their metabolic
demand. This modality is most commonly used for interictal imaging and in this
state the epileptic focus is usually hypometabolic (Figure 3). In some cases,
hypometabolism can be detected in the absence of structural abnormality on MRI.
Figure 3: Axial flourodeoxyglucose (FDG) positron emission tomography (PET)
images obtained in a 19-month-old girl with left occipital electrographic
seizures. The images depict a large region of hypometabolism involving portions
of the left temporal, parietal and occipital lobes.
Another useful functional modality is single-photon emission computed
tomography (SPECT). This is another nuclear medicine derived technique that can
be used to identify a region of epileptogenic brain. It is based on the decay of
a single photon emitting nuclide like Tc
99m
and the images that are
obtained are essentially those of cerebral blood flow, providing an indirect
measurement of cerebral metabolic demand. The most commonly used method is the
ictal SPECT, with the isotope injected during or immediately after a
seizure.
[6]
Ictal SPECT images will usually
demonstrate areas of hypermetabolism in and around the epileptic focus.
S
ubtraction peri
i
ctal
S
PECT
co
-registered to
M
RI (SISCOM) is a recently developed technique that subtracts interictal
SPECT data from ictal SPECT data, then co-registers the difference to the
patient's MRI images.
[7]
This combination
of structural and functional imaging may be most useful in non-lesional epilepsy
cases (Figure 4).
Figure 4: Subtracted periictal single-photon emission computed tomography
(SPECT) coregistered to a structural MRI in a patient with right frontal lobe
seizures. SPECT subtraction shows focal cerebral hyperperfusion in the inferior
right frontal lobe.
Neuropsychological evaluation is another modality used in the presurgical
workup of children with epilepsy. Properly selected testing may be able to
predict cognitive changes that can occur after surgery and assist in the
selection of surgical candidates. These modalities offer yet another method of
studying the functional integrity of the brain and can also help to establish a
preoperative baseline of cognitive function.
Invasive monitoring
Despite many recent advances in the noninvasive workup of epilepsy
surgery candidates, these various modalities can occasionally provide discordant
data or the localization of the epileptic focus may remain unclear. An example
would be a child with EEG evidence of right frontal lobe epilepsy with either
normal imaging or an MRI abnormality in the right temporal lobe. In situations
like this, the epilepsy team may consider other more invasive techniques to
further define and localize the seizure focus. Intraoperative
electrocorticography with cortical mapping is an attractive technique because it
requires only 1 surgery. Its utility is limited, however, in the pediatric
population because a young child may not be able tolerate an awake anesthetic
technique or cooperate when the intraoperative mapping is being performed. For
these reasons and others, extraoperative monitoring with implanted electrodes is
the primary method used to evaluate these patients.
Subdural grid electrodes are surgically implanted arrays of electrodes
that are available in various sizes and configurations. The electrodes are
placed in direct contact with the region of cortex under study and can be
implanted in children of any age (Figure 5).
Figure 5: Intraoperative photograph of subdural grid and strip electrodes
placed over the surface of the exposed right frontal, temporal, and parietal
lobes.
Depth electrodes are implanted into deeper, less accessible areas of the
brain and are used infrequently in children. Regardless of the type of electrode
utilized, after implantation, the child is monitored for several days in an
epilepsy monitoring unit where ictal and interictal data are collected. Ideally,
the seizure focus related to the patient's habitual seizures can be identified.
An additional benefit with this technique is that functional mapping can be
performed. Critical areas of eloquent cerebral cortex can be identified and
mapped by stimulating individual electrodes. This information is then considered
when planning for the resection of the epileptogenic focus. Complications are
infrequent, but can include cerebrospinal leakage, meningitis, elevated
intracranial pressure and hemorrhage.
Surgical intervention
Prior to considering any type of surgical procedure, a complete review of
all historical, semiological, electrophysiological, imaging and
neuropsychological data is performed by specialists at a multidisciplinary
patient management conference. Treatment options are discussed and if it is
decided that surgery is indicated, the appropriate procedure is selected and
preparations can then be made for surgery. An ideal candidate would be a child
with disabling, medically intractable seizures that originate from a single
focus in an area of functionally silent cortex. Resection of an epileptic focus
in such a child has a high likelihood of achieving seizure freedom. If a clearly
defined focus cannot be identified, a disconnection procedure may provide
acceptable palliation. There are a variety of surgical techniques that can be
employed and some of the more common procedures are described here.
Seizures arising from the temporal lobe are the most common type of
medically intractable seizures. There are several distinct temporal lobe
epilepsy syndromes, but the most common in children and adolescents usually
occurs with sclerosis of the mesial temporal lobe structures as the pathological
substrate. These children frequently have a history of an early febrile seizure
and the typical partial complex seizures manifest with staring episodes, manual
automatisms, extension of the contralateral extremities and brief duration. EEG
frequently shows temporal spiking and MRI reveals an atrophic hippocampus with
increased signal on T2 and FLAIR sequences. These seizures are frequently
resistant to medical therapy.
Today, the most commonly utilized technique in these patients is a
2-stage temporal lobectomy during which a variable amount of the anterolateral
neocortex is removed followed by resection of the mesial temporal lobe
structures the amygdala and hippocampus. The extent of neocortical resection
will vary, but in general the anterior portions of the middle and inferior
temporal gyri are removed while sparing the superior temporal gyrus. In selected
older children, intraoperative language mapping with electrocorticography has
been utilized in an attempt to avoid injury to important functional areas.
Major morbidity occurs in approximately 5% of cases and
its effects can be devastating. Transient language deficits secondary to
involvement of the language areas of the dominant hemisphere are not
infrequently observed. These consist primarily of dysnomia and full recovery is
usually seen, particularly in young children. Visual field deficits are observed
and may vary from a superior quadratanopia to a complete hemianopia due to
interruption of the optic radiations in the posterior temporal lobe. Hemiplegia
is uncommon but may occur due to manipulation of or injury to the anterior
choroidal artery as it runs along the mesial surface of the temporal lobe.
Infectious complications are seen infrequently. Despite these significant risks,
many patients and their families will accept the potential for morbidity since
the seizure free outcome rates are quite high. Seizure free rates vary between
series from 78% to 90% with the highest seizure free rates seen in patients with
mesial temporal sclerosis.
[8,9]
One study even demonstrated
improvements in intelligence scores and memory following temporal
lobectomy.
[10]
In general, better outcomes
have been achieved when surgery is performed in adolescents or younger
children.
Partial seizures of extratemporal origin present unique challenges.
Extratemporal neocortical resections are more common in children than in adults
due to the predominance of developmental abnormalities in this age group.
Malformations of cortical development or cortical dysplasias are the most
commonly identified pathological substrates. The principles of extratemporal
resection are similar to other types of epilepsy surgery and outcomes are
improved when structural imaging reveals a clearly defined abnormality. In cases
without a clearly defined abnormality, extraoperative monitoring with implanted
electrodes may be necessary to confirm localization of the epileptogenic zone
prior to surgical resection. Children with frontal lobe pathology tend to do
better overall than children with parietal or occipital lobe involvement since
it is more difficult to define areas of eloquent cortex in the latter, thus
limiting the extent of resection. In general, seizure free rates range from 40%
to 60%. With extensive frontal lobe resections, a dense hemiplegia may result,
but this deficit is usually temporary. Excellent recovery is seen within 6 to 9
months.
In children with diffuse hemispheric seizures or
multifocal unilateral seizures and little functional use of the contralateral
extremities, hemispherectomy or a hemispheric disconnection procedure can
produce dramatic and gratifying results. Many of the children who are considered
for hemispheric epilepsy surgery will have either immature or regressing
neurocognitive development, a manifestation of the frequent seizures and their
deleterious effects on the developing brain. Initial experience with this type
of surgery consisted of the complete removal of all structures within 1
hemisphere with the exception of the basal ganglia. Complications associated
with this technique led to the development of procedures that functionally
disconnect the entire hemisphere while only resecting certain hemispheric
structures. Today, "functional hemispherectomy" can lead to dramatic improvement
in seizure control and in many cases improved neurocognitive development. In
properly selected patients, seizure free rates in children undergoing
hemispherectomy can approach 70% to 80%.
[11]
In some children the goal of epilepsy surgery is not complete seizure
freedom, but rather palliation. Children with atonic seizures have frequent,
harmful drop attacks, which can be significantly reduced with a corpus
callosotomy. The rationale for the procedure is based on the disconnection of
the rapid spread of a focal seizure to the contralateral hemisphere through the
corpus callosum. Seizures are not eliminated, but the rapid synchronization of
the 2 hemispheres is eliminated. More than two-thirds of the patients with drop
attacks who undergo callosotomy will have a substantial reduction in the
frequency or complete elimination of their drop attacks. If the posterior third
of the callosum is spared, a cerebral disconnection syndrome can usually be
avoided.
The newest palliative epilepsy procedure is the use of the vagal nerve
stimulator (VNS). Patients with intractable seizures without an identifiable
focus may benefit from the controlled delivery of electrical stimulation to the
peripheral and central nervous system. The exact mechanism of action of vagal
nerve stimulation is still debated, but reductions in seizure frequencies have
been demonstrated. The procedure consists of implanting a coiled electrode
around the left vagal nerve. A pulse generator is then inserted into the
subcutaneous tissues over the chest wall and programmed externally. Outcomes are
encouraging, but they do not reach the efficacy seen with the common resective
procedures. The VNS is an attractive option, however, because it does not
destroy or remove any cerebral tissue.
Summary
Surgery has become an integral part of the management of
infants, children and adolescents with epilepsy. The various neurosurgical
procedures in use can often produce dramatic and gratifying results.
Unfortunately, surgery is still regarded by many as a treatment of last resort
reserved for the child at the end stage of multiple diagnostic decisions. With
improvements in neuroimaging techniques and evaluation procedures, more children
are being identified with intractable seizures that may be amenable to surgical
treatment. In a child in whom a reasonable trial of antiepileptic drugs has
failed to provide adequate seizure control, referral to a pediatric epilepsy
center should be considered.
References
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Walczak TS,
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