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ILAE Commission on Neurosurgery
– H.G. Wieser, Chair
The non-pharmacological treatment of the epilepsies consists
of epilepsy surgery, behavioral therapies, and dietetic measures.
In recent time some ‘experimental’ methods or
treatments ‘in evaluation’ have enriched the
armamentarium, such as radiosurgery, in particular Gamma-Knife,
deep brain stimulation (DBS), transcranial magnet stimulation
and transplantation surgery. Epilepsy surgery has met with an increased interest but
is still underutilized in most countries, particularly third-world
countries. In so-called developed countries the availability
of advanced non-invasive diagnostic tools to delineate epileptogenic
lesions and epilepsy related functional deficits, and to
prove epileptogenicity, has partly improved this situation.
These modern diagnostic tools, together with improved surgical
techniques, have translated into better postsurgical outcome
figures and into a larger population of difficult-to-treat
patients profiting from surgical therapy. In parallel one
can recognize an important role of epilepsy surgery within
the modern neuroscience field. Epilepsy Surgery The classical ‘open’ epilepsy surgery can be
(and was) described at three levels. The first category differentiates
between ‘lesion-oriented surgery’, ‘epilepsy-oriented
lesional surgery’ and ‘epilepsy surgery sensu
stricto’. The second category differentiates between
individually ‘tailored’ and ‘standardized’ procedures,
such as anterior temporal lobe resection, selective amygdalohippocampectomy,
and anterior callosotomy. It is obvious that also so-called
standardized operations are most often somewhat tailored,
based on preoperative findings as well as on intraoperative
electrocorticography (ECoG) and other intraoperative neurophysiological
tests (functional mapping). Individually tailored operations
comprise topectomies and larger resections. The third category
differentiates between ‘curative
(causative)’ and ‘palliative" surgeries. ‘Curative’ means
that the goal of the operation is complete freedom of seizures,
i.e., the intention is the complete resection of the seizure
generating area. ‘Palliative’ means that an amelioration
of the seizure tendency, but no cure, is expected, because
the seizure generating area cannot be entirely resected.
Into the latter category fall the transection of pathways
important for spread of the seizure discharges (as is the
case in corpus callosum section, and the multiple subpial
transection (MST, Morrel-Whisler), and the resection of secondary ‘amplifier
structures’ (as is the case in palliative amygdalohippocampectomy).
Also the vagus nerve stimulation (VNS) can be included here. Curative, Resective Surgery The efficacy of resective epilepsy surgery in temporal lobe
epilepsy and some forms of extratemporal epilepsy surgery
in patients with focal epilepsy uncontrolled by antiepileptic
drugs is undisputed. Uncontrolled epilepsy is associated
with progressive cortical and hippocampal atrophy, substantial
cognitive and psychosocial morbidity, and increased mortality.
Seizure freedom is required to reverse such morbidity and
mortality. Surgery is vastly superior to medical therapy
for patients with chronic, refractory temporal lobe seizures,
and is now the standard of care for these patients. Evidence
from a recent randomized controlled trial of surgical versus
medical therapy of temporal lobe epilepsy proves that antero-mesial
resection is safe and more effective than medical therapy.
The number of patients needed to treat for one patient
to become free of disabling seizures is two, which is superior
to most interventions in neurology. A meta-analysis of
non-randomized trials gives almost identical results; about
two-thirds of patients become seizure-free, compared with
only 8% with medical therapy. The results are remarkably
similar among studies from different parts of the world.
Quality of life improves early after epilepsy surgery,
the improvements are both statistically and
clinically significant, and they are sustained. Surgical
morbidity with clinically important permanent sequelae
is 2%. Nevertheless, epilepsy surgery remains underutilized
in developed countries and it does not exist in all but
a few developing countries. Current randomized trials are
underway to explore the effect of early surgery versus
optimum medical therapy on the prevention of disability
in patients with mesial temporal lobe epilepsy, and to
examine the effectiveness of novel interventions, such
as minimally invasive surgery and brain stimulation. Although
the concept of early surgery requires further exploration
and definition and, at present, there is no robust, direct
evidence to support early epilepsy surgery, case series
and cohort studies report an association between earlier
surgery and better outcomes. Outcome predictors: Extensive reviews of the literature
since 1990 on the effectiveness of surgery for antero-mesial
temporal lobe exist (Engel et al. 2003; McIntosh et al. 2001)
and many of the more recent studies tried to identify variables
(outcome predictors / risk factors) associated with postoperative
outcome. In the systematic literature review of 126 articles
published between January 1991 and April 2000 on temporal
lobe surgery outcome, McIntosh et al. (2001) found that 97
studies tested the relationship of at least one factor with
outcome by using statistical analysis. Preoperative variables
(aggregated into six major groups according to general subject)
were clinical features, electroencephalographical (EEG and
ECoG), preoperative magnetic resonance imaging (MRI), preoperative
functional imaging, histopathology findings, and operative
factors. Such studies on predictors of epilepsy surgery outcome
have helped to better advise patients at an early stage of
their disease. Mesial temporal lobe epilepsy with hippocampal sclerosis
(MTLE-HS) is the most important type of epilepsy in surgical
series. At the May 2002 expert Meeting in Istanbul on MTLE-HS
(Wieser 2004) experts discussed in depth the underlying causes
and how to diagnose and treat this syndrome. Concerning treatment
it was concluded that in the presence of unilateral MTLE-HS
the extent of mesial resection correlates positively with
seizure outcome. However, ‘extent’ of mesial
resection needs precision. Surgical series where only the
anterior part of the hippocampal formation (pes) or no hippocampus
was removed indicate less seizure control than when most
of the hippocampal body along with the pes and parahippocampal
gyrus is removed. Except for the study of Wyler et al. (1997)
direct comparisons of different surgical resections have
not been done in a prospective surgical series to compare
seizure control (short-and long-term, and for differences
in neurocognitive skills). In the prospective, randomized,
blinded clinical trial of Wyler et al. seizure and neuropsychological
outcomes from anterior temporal lobectomies were compared
between two groups of patients. One group underwent hippocampal
resection posteriorly to the anterior edge of the cerebral
peduncle (partial hippocampectomy). In the other group, the
hippocampus was removed further to the level of the superior
colliculus (total hippocampectomy). The amount of lateral
cortical resection was the same between groups. At 1 year
postoperatively, the total hippocampectomy group had a statistically
superior seizure outcome compared with the partial hippocampectomy
group (69% versus 38% seizure-free), and examination of time
to first seizure revealed significantly superior outcomes
associated with total hippocampectomy. There was no increased
neuropsychological morbidity associated with the more extensive
hippocampal resection. Therefore, if there is evidence for
the presence of MTLE-HS the hippocampal formation and in
most instances the anterior parahippocampal gyrus should
be resected after careful evaluation of the remaining functions
of the to-be-resected structures. However, the amount of
amygdala that needs to be resected in MTLE-HS is unknown. Outcome for MTLE-HS might be associated with the severity
and type of HS (‘classical’ HS with neuron cell
loss and gliosis in CA1, CA3, and the granule cell layer
of the dentate gyrus, with relative sparing of the CA2 region
versus ‘nonclassical’ (diffuse) HS, sometimes
extending into temporal polar regions) patients, but further
studies are necessary to provide convincing evidence and
possible confounding variables have to be taken into account
(Wieser et al. 2003). There is controversy about the need to resect lateral temporal
cortex in the presence of MTLE-HS. From the systematic review
of McIntosh et al. (2001) there is no indication that extent
of lateral neocortical resections correlates with seizure
outcome. Consequently several centers no longer resect neocortical
lateral temporal cortex and claim that seizure outcomes with
restricted mesial resections are at least as good as with
more extensive temporal lobe resections. However, until now
no convincing studies exist that show that more selective
mesial resections are correlated with better neuropsychological
outcomes, although this has been claimed and might be the
case. It is likely that the more selective surgery causes
less memory problems than standard two-thirds anterior temporal
lobe resection. However potential collateral cortical damage
due to the approach must be considered a potential source
of additional memory impairment in highly selective mesial
resections. The cognitive consequences of sparing not only
the lateral cortex but also mesial structures apart from
the hippocampus or of tailored hippocampal resections are
not yet known. Likewise there is controversy whether tailored
resections using pre-/post intraoperative recording improves
seizure outcome. In the presence of circumscribed foreign tissue lesions,
such as ganglioglioma, DNET and other low-grade tumors a
lesionectomy might suffice in certain instances. If there
is evidence for ‘secondary’ HS or ‘dual
pathology’, it is recommended to resect both the foreign
tissue lesion and the gliotic hippocampus. In patients with
dual pathology, removal of both the lesion and the atrophic
hippocampus is the best surgical approach and should be considered
whenever possible since hippocampectomy alone and removal
of the lesion alone yield unsatisfactory results. An accepted
definition of dual pathology is, however, still lacking.
Therefore, the concept of ‘dual pathology’ needs
further clarification.
Seizure outcome in MRI-negative patients and in patients
without histopathological abnormalities in the resected specimen
is poor. Outcome may be good in MRI-negative patients with
temporal hypometabolism on FDG-PET, who usually do show histopathologic
abnormalities. Long-term actuarial analysis of outcome is
a necessary next step for future studies. Thus, while not
optimal, cryptogenic cases (defined as no significant pathology
on imaging and histology) are still surgical candidates if
the risk-benefit analysis is acceptable to the patient and
family. The actuarial analysis of Berkovic et al. (1995) showed
that outcome at postoperative year 5 is different for MTLE-HS
compared to other forms of temporal lobe epilepsy: 5 years
after surgery 21% with normal MRI had no postoperative seizures
versus 50% with hippocampal sclerosis, and 69% of patients
with foreign tissue lesions. Similarly, an eventual seizure-free
state of 2 years or more, whether the patient was seizure-free
since surgery or not, was achieved by 36% of those with normal
MRI, versus 62% of those with HS, and 80% of patients with
foreign tissue lesions. Long-term relapse. More research is needed to determine
if patients with HS are more likely to experience late seizure
recurrence. Data previously published from patients with
long-term follow-up analyzed up to 1996 found that medial
temporal resections had a higher rate of long-term relapse,
but this remains open to further prospective studies. Extratemporal Epilepsy Surgery Extratemporal epilepsy surgery is usually a tailored
surgery and very often associated with lesions. Frontal epilepsy
surgery prevails in this category. Non-lesional extratemporal
epilepsy surgery usually requires extensive invasive presurgical
evaluation, which differs from patient to patient according
to the non-invasive findings. Invasive EEG with grid- strip-
and depth-electrodes, often in combination, is necessary
to delineate the epileptogenic seizure onset zone. Results
in extratemporal epilepsy surgery are inferior to temporal
lobe surgery. From the data collected by Engel et al. (1993)
at the 2nd Palm Desert Conference out of a total of 8234
operations only 13% were extratemporal. In non-lesional
extratemporal epilepsies circumscribed topectomies are
rarely successful; more often rather extensive resections
are required to render a patient seizure-free. The complete
resection of the epileptogenic zone is very often hindered
by the fact that the epileptogenic seizure-generating zone
extends into indispensable functional cortex. In such instances
multiple subpial transection can be considered. Hemispherectomy Today standard anatomical hemispherectomy has given place
to the so-called ‘functional hemispherectomy’ (Adams
1983; Rasmussen 1973, 1983; Villemure et al. 1993). Rasmussen’s ‘functional
hemispherectomy’ technique is a subtotal hemispherectomy,
i.e., removal of the temporal lobe and central region, and
disconnection of the residual frontal and parieto-occipital
lobes from the rest of the brain. Schramm et al. (2001) described
the so-called ‘transsylvian keyhole functional hemispherectomy’. Indications for hemispherectomy are severe unilateral epilepsies
of childhood with unilateral neurological deficits (hemiparesis
and hemianopia), hemimegaloencephaly, infantile type hemiplegia
and seizures (HHE), Rasmussen’s encephalitis, and Sturge-Weber-Syndrome.
Marked preoperative neurological deficits should be present
before considering this radical operation. If performed early
and with appropriate indication results of functional hemispherectomy
are in general very gratifying, i.e., most children profit
quite a lot. Corpus Callosotomy (CCT) Callosotomy is based on the principle of preventing generalization
of seizures. It should be considered in pharmacoresistant
epileptic conditions where no circumscribed cortical excision
is possible because of extended badly localized epileptogenic
seizure generating zone(s). Ictal EEG findings are, however,
lateralized with rapid generalization (so-called ‘secondary
bilateral synchrony’). Clinically, candidates for callosotomy
suffer usually multiple seizure types, but those with severe
sudden falls are said to respond best to this surgical approach. CCT using Gamma Knife is possible as shown by the Graz group.
However, further studies are necessary to define the role
of classically performed CCT versus Gamma Knife CCT versus
VNS. Multiple Subpial Transection (MST) In a meta-analysis Spencer et al. (2002) collected 211 patients
from 6 large epilepsy centers operated on with MST, but only
53 had no additional resection (MST-). In patients with MST
and resection (MST+) in 87% a >95% seizure reduction was
obtained for generalized seizures, a 68% reduction for psychomotor
seizures and a 68% seizure reduction for simple partial seizures.
For MST results were less good. A >95% seizure reduction
was obtained for generalized seizures in 71%, for psychomotor
in 62% and for simple partial seizures in 63%. EEG localization,
age at onset of epilepsy, duration of
epilepsy, and localization of MST were not significantly
correlated with the result. Surgery related neurological
deficits were present in 47 patients, in MST+ (23%)
in MST- (19%). Experimental Procedures or Epilepsy Surgical Techniques
in Evaluation. Besides intermittent vagal nerve stimulation (VNS), transcranial
magnetic stimulation and deep brain stimulation, as well
as attempts of transplantation of fetal or genetically engineered
inhibitory active cells into the epileptogenic focus have
been started. Whereas stereotactic procedures – with the exception
of amygdalotomy in the extremely rare amygdalar seizure onset
epilepsies – are no longer generally accepted, some
subthalamic and thalamic targets have been recently rediscovered
within the field of deep brain stimulation (DBS). Some tumor-associated
focal epilepsies of delicate locations (insula of Reil and
hypothalamic hamartoma) may profit from radiosurgical approaches,
such as the Gamma Knife and interstitial 125-iodine radiosurgery
of low-grade gliomas by seed-implantation. Arguments for
radiosurgery are lower mortality and morbidities with equal
efficacy with regard to seizure
outcome and quality of life. In principle today Gamma Knife,
linear accelerator and Cyclotron techniques are available
and competing. In the field of so-called non-lesional (non-tumoral)
epilepsy surgery only with the Gamma Knife technique has
a reasonable experience accumulated with at least some – albeit
limited – long-term data. Studies are presently conducted
to define the role of Gamma Knife for the treatment of MTLE-HS. Concluding Remarks Epilepsy surgery is playing an increasingly important role
in the epileptologist's therapeutic armamentarium. In one
part this is due to the considerable improvement in structural
and functional imaging and electrophysiological techniques,
particularly EEG long-term monitoring. The other reasons
are a better understanding of the pathophysiology of those
epileptic conditions, which are amenable to surgery, and
refinements in surgical (and radiosurgical) techniques. Today
reasonably reliable prognosis can be made prior to the recommendation
of surgery based on worldwide collected inclusion and
outcome data. Whereas careful and knowledgeable presurgical evaluation
of candidates of epilepsy surgery still remains the most
important step, there is no doubt that today a
considerable number of patients can undergo successful surgery
without invasive intracranial presurgical procedures, resulting
in an improved cost-effectiveness and in a growing utilization
of this kind of therapy in countries with limited resources. Whereas for years epilepsy surgery has been considered a
kind of ‘last resort’ for many doctors, surgical
treatment for epilepsy is nowadays an evolving and accepted
discipline. It is hoped that the resulting growth in basic
research on the epileptic human brain and improved surgical
techniques result in further improvement in the
treatment of certain types of epilepsy. On the other hand,
experience shows that quality control in epilepsy surgery
is very important. Worldwide collaboration and the establishment
of national centers of reference for epilepsy surgery are
probably the best way to guarantee observation of high and
accepted standards. The ILAE Commission on Neurosurgery for
Epilepsy is challenged!
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