ARTICLE
Paper presented at the World Conference on Pediatric Neurosurgery
2000: State of the Art and Perspectives for the Third Millenium, Martinique,
27 November to 4 December 1999.
Surgical therapy of epilepsy in adults has now gained full acceptance,
at least in developed countries. It has the advantage, when successful,
of being a definitive treatment not only preventing the harmful consequences
of uncontrolled, repeated seizures but also allowing the use of smaller
dosages of antiepileptic drugs or even their discontinuation. Such benefits
would appear to be of even greater importance for children in whom the
benefits could extend over a lifetime. In spite of these potential advantages,
epilepsy surgery in children has been slow to develop and the interval
between onset of the disease and surgery in patients is still often very
long, 10-15 years or more [1]. Nevertheless, over the past two decades,
considerable work has been dedicated to epilepsy surgery in young patients
[2-5]. It has been recognized as both justified, because the outcome in
childhood epilepsies became predictable, and possible, thanks to the introduction
of new techniques of exploration, especially modern neuroimaging.
As a result, epilepsy surgery programmes have been launched in most
major paediatric centres. Application of surgical therapy to childhood
epilepsies, however, raises problems different to those in adults not
only for technical reasons, but even more because the disorder occurs
in a developing, constantly changing organism and can modify its ultimate
functioning, and because early-onset epilepsies may differ considerably
from their adult counterparts. This article analyses the causes of these
differences and considers some of the unresolved issues raised by paediatric
epilepsy surgery.
Required conditions for
surgical treatment
Three conditions are necessary for surgical treatment of epilepsy, whether
in adults or in children: 1) medical intractability of the disorder; 2)
feasibility of surgery; 3) likelihood of a satisfactory result, in terms
of both cure or improvement of the disorder and reasonable preservation
of brain functions. Practical implementation of these conditions can be
considerably different in adults and children.
Intractability, defined as "inadequate seizure control in spite
of appropriate medical therapy with antiepileptic drugs or adequate seizure
control but with unacceptable side-effects from the AEDs" [6, 7] is a
rather vague concept. What constitutes "inadequate seizure control" or
"unacceptable side-effects" depends not only on biological facts but on
an appreciation by the patient that may vary according to her/his lifestyle
and personal objectives. It is therefore a joint decision of the patient
and doctor taking into account both medical and personal factors, and
is therefore highly individual.
In children, the issue is even more complicated and many factors specific
to infant and childhood epilepsies make a simple transposition of rules
in adults inappropriate. Even though epilepsies after 4-5 years of age,
especially partial symptomatic ones, can be approached in the same general
way as in adults as they raise generally similar problems although the
possibilities and techniques of presurgical exploration may differ, the
situation is radically different in many other cases [8]. One major problem
is the stability of the epilepsy. It has long been known that some children
"grow out" of their epilepsy and are thus not candidates for epilepsy
surgery. Considerable work over the past 20 years has established criteria
that separate the benign epilepsy syndromes from the severe or malignant
ones [9]. It is now possible to know, early in the course, whether persistence
of seizures is likely and whether epilepsy will interfere with cognitive
and behavioural development, and therefore to establish a firm prognosis.
Syndromes with excellent prognoses such as benign rolandic epilepsy or
benign occipital epilepsy [10] can now be easily distinguished from more
severe cases and there is little risk of advising surgery in such cases.
The characterization, from clinical and EEG points of view, of malignant
epilepsy syndromes such as West syndrome, Lennox-Gastaut syndrome, severe
myoclonic epilepsy or polymorphic epilepsy of infants casts a different
light on infantile and early childhood epilepsies. In this new perspective,
seizures are not necessarily the only or even the main problem; cognitive/behavioural
development is of paramount importance. This has to be taken into account
in the therapeutic decision and, even though the role of surgery in this
respect remains to be established, an early interruption of the epileptic
activity is clearly desirable. Most infant and childhood epilepsies are
severe, with multiple, daily seizures and specific EEG changes, so the
intractable nature is rapidly determined without the necessity of waiting
2 or 3 years [11].
Feasibility. Several studies have shown that epilepsy surgery
is perfectly feasible in children and infants [12-19] provided a trained
team including child neurologists, electroencephalographers, neuropsychologists
and specialists in imaging in young patients is available, in addition
to the neurosurgeon(s) and anaesthesiologists. However, the types of surgery
to be performed are often different from those in adults because the lesions
responsible for epilepsy syndromes are often extensive (e.g. involving
more than one lobe or a whole hemisphere), leading to large resections
especially hemispherectomies and similar techniques. For several syndromes,
such as Landau-Kleffner [20], or some cases of bilateral epileptogenesis,
only palliative surgery such as corpus callosotomy can be considered [21].
In general, the pathology responsible for the epilepsy is different in
adults and children. Hippocampal sclerosis, for example, is less common
in children than in adults [15, 16], although recent work has shown that
it is not rare [24]. Tumours are much less common in children and are
mostly represented by developmental lesions such as ganglioglioma [22,
26, 27] or developmental neuroepithelial tumours (DNET) [24] that do not
pose oncological problems as they are static or very slow growing, but
pose mostly an epilepsy surgery problem, i.e. that of the extent
of resection necessary for an optimal result. Cortical dysplasias are
the most common cause of refractory epilepsy at this age [16, 19]. Their
frequency may be responsible for the common occurrence of extratemporal
lesions that pose difficult problems. In addition, the extent of cortical
dysplasias is often difficult to define with current techniques. The possibility
of other subtle, undetectable, abnormalities in the rest of the brain
[25] may be one reason for the relatively poor surgical results in some
series. These conditions remain a challenge for epileptologists and surgeons,
to improve the techniques of diagnosis (e.g. by improvements in
anatomical and functional imaging) as well as operative methods.
The approach of such lesional epilepsies has
been revolutionized by the new techniques of neuroimaging that play a
decisive role in modern epilepsy surgery [29]. MRI is the most commonly
used of these techniques and is being constantly improved. Functional
imaging (positron emission tomography (PET), single photon emission computed
tomography (SPECT), magnetic resonance spectroscopy (MRS) and functional
MRI (fMRI) are becoming increasingly important for determination of epileptogenic
areas and of functionally eloquent cortex. Modern computing techniques
allow the combination of several modalities in the same image and comparison
with mean results from groups of normal subjects (statistical parametric
analysis) [30]. Progress in imaging combine with EEG techniques to give
a precise definition of the epileptogenic zone(s). Advanced scalp EEG
methods and combination with video-recording are widely available and
a large variety of invasive recording techniques can be used. Their feasibility
in young children and in behaviourally disturbed patients, however, continues
to raise problems and still represents a limitation in the investigation
of some cases of epilepsy with negative MRI and therefore in the feasibility
of surgery in these cases.
Likelihood of satisfactory results. Results of epilepsy surgery
on control of the seizures from various centres are comparable to those
of most adult series [15, 19, 26]. It is, however, important to separate
results in older children in whom surgery is not fundamentally different
from that in adults, from those in infants and younger children less than
3-4 years of age for whom the indications and surgical techniques are
often very different.
Such information is still relatively limited [8, 16, 18, 19]. Excellent
results (Engel grade I) are reported in 35% [16] to 61% [15, 19] of infants
less than 3 years of age at the time of surgery. Results are better for
cases of tumours or Sturge-Weber syndrome than for cortical dysplasias
or hemimegelancephaly in some, but not all, series [16, 31]. As in older
patients, the results of surgery in general are significantly better when
a dectectable lesion can be demonstrated by neuroimaging. The results
of temporal lobe surgery are better than those of extratemporal resection,
and those of hemispherectomy seem superior to those of focal resection
in some series. In fact, comparison between reported studies are difficult
because of the heterogeneous composition of series, different methods
of selection and investigation, and variable causes of seizures. Furthermore,
the very aim of surgical therapy in young infants need not be the same
as in older patients.
Indeed, total control of seizures has been shown in older patients to
be an absolute requirement for an excellent outcome in terms of quality
of life [31]. In children, it may be especially important that control
is obtained early, as the psychosocial consequences of epilepsy and its
treatment are of great significance in terms of ultimate development and
social insertion. For infants, however, other aims of surgery are conceivable.
One would be the prevention of cognitive and behavioural deterioration
or arrest of development, if it can be demonstrated that even subclinical
epileptic activity (especially some EEG patterns such as hypsarrhythmia
or continuous spike-waves of sleep) may be responsible and respond to
surgery. Incidentally, this would raise the question of whether to operate
on infants, even in the absence of seizures, in cases of progressive deterioration
with such severe EEG patterns. Another objective would be the palliation
of certain consequences of epilepsy, for example repeated falls, that
are extremely disruptive for the patient and family life, even when curative
surgery cannot be contemplated. Operations such as commissurotomy and
subpial transections could be considered for such aims. Such a widening
of the potential scope of surgery would have to be assessed on criteria
different from those in conventional resective surgery. Establishment
of different categories for measuring the outcome of epilepsy surgery
in children, based not only on seizure control but on cognitive/behavioral
improvement (or arrest of deterioration) and on improvement in the overall
quality of life would be required, especially for the unfavourable categories
for which complete seizure control may be unattainable but significant
alleviation of the worst consequences of the disorder might be achievable.
Taylor et al. [31] have proposed such a scheme and further reflection
along these lines is needed.
Future perspectives
Even though successes of surgery in the treatment of epilepsy have been
gratifying, there is ample room left for further research and improvement.
One important topic for research is assessment of the results of surgery.
The significance of currently published results is hard to evalulate as
many studies are obviously not comparable and the results probably depend
as much or more on the criteria for acceptance of surgical candidates
than on the methods of investigation or operative techniques used. Centres
that operate on relatively "poor" candidates such as patients with mental
retardation, cerebral palsy or extensive lesions will have less favourable
statistics than those that accept only rigorously selected patients of
the "best" category. This has a clear impact on the extent to which surgical
therapy can be used: should it be reserved for a selection of relatively
unusual patients with a high probability of good control and great benefit,
in terms of quality of life and social insertion, or is it acceptable
to include a larger number of patients with a less favourable prognosis
both in terms of seizure control and of quality of results? It is clearly
difficult to give an absolute answer as the issue is not purely medical
but has to be also evaluated according to the cost to society and burden
imposed on patients.
A somewhat similar issue arises with respect to the indications of the
multiple methods of investigation for surgery. While clinical examination
is of accepted importance and the depth of investigation is very much
guided by the individual problem of each patient, there is still some
debate about the more or less completeness and technicity required. For
example, is invasive EEG recording (SEEG or otherwise) necessary for all
or a majority of cases or can investigation be simplified in a significant
proportion? Again, there is no simple answer, in large part because comparisons
are not available which take into account not only the crude statistics
but also the comparability of operated patients. Some studies indicate
that, even with a well-defined lesion, the use of operative intracranial
recording improves the results [15, 23, 30, 35] but the cost of complicated
techniques is great both in terms of resources, human and material, and
of human factors such as duration of hospitalisation and repeated investigations.
The actual benefit is difficult to measure as the degree of experience
of a team may be as important for some matters as the technical tools
they use. I believe that a considerable effort should be made to try to
devise methods that could help answer these questions.
The place of techniques other than resection
surgery in treatment also demands further research. Such methods do not
directly compete with resection in terms of control of seizures, so their
possible benefit requires a different assessment. Some may have a relatively
high degree of effectiveness for control of seizures and can therefore
be assessed like more classical techniques, e.g. amygdalohippocampectomy
which may be used palliatively in some temporal lobe tumours. Others,
such as commissurotomy, are basically meant to limit the damage from seizures
and have a rather narrow scope. Their usefulness appears to be relatively
limited and better techniques should be looked for. Still other methods,
especially subpial transection, are being used in several centres for
the treatment of epilepsies in which the epileptogenic area cannot be
resected without major functional deficits. The underlying assumption
is that recruitment necessary for generating an epileptic discharge is
mediated by horizontal fibres that are interrupted by the procedure, whereas
vertical fibres that mediate the functions are left untouched [20]. The
effectiveness of the procedure is still being evaluated. An additional
interest of this method is to suggest that some surgical procedures might
have a positive effect on functional deficits not directly related to
clinical seizures. Suppression of the underlying epileptic discharge would
allow resumption of the normal function suppressed by the massive and
unmodulated paroxysmal activity. A possible mechanism to explain the persistence
of deficit after a long-lasting period of epileptic activity even without
clinical seizures, is that the epileptic activity as expressed by the
EEG can modify the connectivity of the cortical areas involved and interfere
with their specialisation. Clearly, much more needs to be known about
possible mechanisms, but the possibility of interfering surgically with
an abnormal function in order to restore a more normal activity is both
intriguing and exciting as cognitive and/or behavioural deterioration
is one of the major issues in infant epilepsy. Whether the method is effective
and whether it can be extended to other areas and pathologies remains
to be determined. Finally, vagus nerve stimulation is being intensively
studied for patients not amenable to any form of surgical treatment and
preliminary results seem interesting [7].
CONCLUSION
The recent developments in surgical treatment of epilepsy in childhood
suggest that its indications may need to be redefined in several respects.
Firstly, the good results obtained lead most investigators to propose
surgery as an early, if not a first option. This would apply especially
to some syndromes such as mesial temporal lobe epilepsy following febrile
seizures for which surgery could even be considered as indicated, as a
first treatment or at least after only a brief attempt at medical control.
Clearly, there is no reason to procrastinate when a definitive treatment
is available with a high likelihood of cure. However, a more complete
assessment of the possible adverse effects of resection, especially on
memory [17], is necessary before this approach can be recommended.
Secondly, the domain of surgery may possibly be extended to patients
so far excluded. These could include patients with disorders in which
localisation of the responsible lesion(s) is currently imprecise, such
as tuberous sclerosis, patients with multiple disabilities for whom even
partial relief of seizures can improve their quality of life, and some
of those with threatening or ongoing cognitive behavioural deterioration
such as infantile spasms, the Lennox-Gastaut syndrome and other epileptic
encephalopathies, if adequate methods of exploration and treatment can
be devised.
Thirdly, efforts should be made to reduce the cost of surgery, both
in terms of personal suffering and of human and financial resources. This
implies a minimum agreement on the best techniques for specific problems,
thus the possibility of comparative studies among the different methods.
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