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Epilepsy surgery Is it an effective treatment.

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ISSUES I N CLINICAL NEUROSCIENCE
Epilepsy Surgery: Is It an
Effective Treatment?
Richard M. Dasheiff, M D
Epilepsy surgery is now considered an acceptable treatmen\ for patients who have medically intractable seizures. Epilepsy surgery centers are appearing like
mushrooms after a long period of cool weather and
much rain. This new infatuation with epilepsy surgery
in America and Europe is likely to be a mixed blessing.
The advantages should include more and better care of
patients with all types of epilepsy, a raised social consciousness about epilepsy (which is still in the closet),
and advances in the clinical and basic science aspects of
brain function. The disadvantages could include the
delivery of inferior services to patients caused by a gap
between the academic institutions that developed the
techniques and the community hospitals that try to use
them. The expense of epilepsy surgery could funnel
monies away from other worthwhile programs. Lastly,
epilepsy surgery may not be a satisfactory treatment
for patients with medically intractable epilepsy. The
purpose of this article is to discuss this last issue.
There currently exists a great diversity of approaches in the presurgical evaluation for epilepsy
surgery, in the types of operations performed, and in
the methods and standards of determining outcome
{ 1). The efficacy of epilepsy surgery for nonneoplastic,
cortical resection has not changed substantially over 50
years. On a clinical level the results are not significantly
different, based on the lobe involved, the method of
surgery, the method of presurgical evaluation, and
other variables that have been analyzed. These statistics and lack of improvement in the field were the
focus of an international meeting {l). The National
Institutes of Health recently decided to solicit proposals to address these issues. N o one, however, has proposed that the most important question be asked: Is
epilepsy surgery a worthwhile treatment for patients?
Worthwhile means not only reducing or stopping seizures, but also making a positive difference in the patient’s life.
The efficacy of epilepsy surgery has never been assessed in a prospective, randomized clinical trial. In fact,
no clinical trials have been done on any aspect of
epilepsy surgery. Although there are multiple reasons
for this, the key reason is that everyone in the field of
epilepsy now believes that the natural history of medically intractable epilepsy is known, and surgical treat-
From the University of Pittsburgh Epilepsy Center, Pittsburgh, PA.
Received Jun 14, 1988, a d in revised form Aug 10. Accepted for
publication Oct 2, 1988.
ment produces statistically better results than medication alone. The data that have been used to support
the efficacy of epilepsy surgery for partial seizures will
be examined.
The treatment of simple and complex partial
epilepsy is far from successful in controlling most patient’s seizures [2-4). Optimal control of epilepsy is
when the patient experiences no seizures (including
auras) and has no adverse side effects from the treatment. New antiepileptic drugs have not appreciably
altered the success rate for controlling seizures [3,5,6].
Using conservative figures that one million Americans
have epilepsy, that two-thirds have partial epilepsy, and
that in one-third medical management fails and half
of them may have been suitable candidates for epilepsy
surgery, we can estimate that 100,000patients are possible candidates for surgical treatment. If the mean cost
of a presurgical evaluation, surgery, and follow-up is
$50,000, then it would require a five-billion-dollar expenditure to treat these patients. Using an incidence
rate for epilepsy of 30/100,000 and the same proportions as just mentioned, we arrive at an estimate of
7,500 new surgical candidates per year at a cost
of $375,000,000 yearly. The expenditure of billions of
dollars for this treatment would be justified only if the
treatment is more effective than medical management.
The efficacy of epilepsy surgery has been claimed to
be 80%, which includes both the patients who are seizure free and those who are significantly improved. The
patients who are classified as free of seizures may still
include those with auras and those taking medication.
Those improved include patients who are having seizures
that have decreased in frequency by 75% or more.
They are invariably talung antiepileptic drugs (AEDs).
A review of the literature is summarized in the
Table. A third of patients (range, 9 - 4 4 s ) who received epilepsy surgery had no improvement in the
control of their seizures. Another third (range, 1446%) improved but still required AEDs. For the best
results, one-third (range, 21-65%) were reported as
seizure free. Yet most of the people in this group still
had epilepsy. Some were truly seizure free but required
AEDs. The expense for medication and physician visits
was not eliminated, and neither was the morbidity associated with remaining on AEDs (side effects, selfesteem). Additional patients continue to have seizures
(auras) which further remind the patient and the physician that the surgery was not completely effective. Because of the high cost of epilepsy surgery, and its rare
but serious complications (infections, permanent
neurological deficits, and death) is it not fair to ask
Address correspondence to Dr Dasheiff, University of Pittsburgh
Epilepsy Center, 3515 Fifth Ave, Rm 625, Pittsburgh, PA 15213.
506 Copyright 0 1989 by the American Neurological Association
Surgery Results (Minimum2-year Follow-up)
Resultsb
Group, Year Published/
Population Studied and Epoch”
NIH, 1975 181
100% temporal (1954-69)
Seattle, 1986 [14]
87% temporal (1973-83)
UCLA, 1986 [l5]
100% temporal (1961-82)
Georgia, 1986 [161
100% temporal (1981-83)
Yale, 1985 [17)
100% frontal (1973-85)
Oregon, 1985 El81
temporal and frontal (1983-85)
Zurich, 1983 1197
100% temporal (1969-79)
Dublin, 1988 [20)
100% lateral temporal (1976-86)
Paris, 1974 121)
100% frontal (1957-73)
Paris, 1974 [21)
100% central (1957-73)
Paris, 1974 [21]
100% parietal (1957-73)
Paris, 1974 [2l]
100% temporal (1957-73)
Paris, 1974 [21)
100% stereotaxic (1957-73)
Oxford, 1987 [22}
100% temporal (1972-83)
MNI, 1975 [81
100% temporal (1930-7 1)
MNI, 1975, 1983 C23, 241
100% frontal (1930-7 1)
MNI, 1975 [25}
100% parietal (1930-71)
MNI, 1975 [251
100% sensorimotor (1930-71)
MNI, 1975 [251
100% occipital (1930-7 1)
MNI, 1975 [26]
100% cortical (1928-7 1)
MNI, 1983 [271
100% cortical (1928-80)
15 series excluding MNI [8}
cortical (1953-70)
Palm Desert, 40 centers, 1987 191
anterior temporal lobectomy (1949-84)
Palm Desert, 32 centers, 1987 197
extratemporal (1949-84)
Total No. of
Patients
Seizure-Free (%)
Improved (%)
Not Improved (%o)
21
46
33
124
40
26
34
100
46
35
19
75
65
22
13
23
60
20
20
5
48
43
9
44
57
27
14
35
46
22
32
37
48
14
38
21
36
28
36
14
46
22
32
28
64
20
16
66
23
42
35
26
62
21
17
58
41
28
31
627
24
32
44
212
31
22
41
86
31
26
43
63
26
43
32
19
39
28
33
1112
37
26
37
894
39
33
28
769
55
28
17
2336
43
28
29
82 5
,
“Group specifies where the surgery was done. UCLA = University of California at L o s Angeles, NIH = National Institutes of Health, MNI =
Montreal Neurological Institute. Population studied: if surgery involved temporal lobe in all patients, designation of 100% temporal is used; if
surgery involved different lobes (temporal, frontal, etc) in the patients, but 87% involved the temporal, then the designation is 87% temporal.
bSeizure free means patient may have auras and be taking AEDs; improved means 75% reduction in seizures; not improved means less than
75% reduction in seizures.
Issues in Clinical Neuroscience: Dasheiff: Epilepsy Surgery 507
what percent of patients have been cured? Unfortunately, these data are unavailable in the published
literature.
It will be argued that the quality of life was improved for those patients in whom seizure control was
improved. However, even one complex partial seizure
a year would preclude them from driving a car in most
states. The University of Pittsburgh‘s experience with
surgically treated patients, and the reports in the literature [7, 81, suggest that these patients do not necessarily move up the socioeconomic ladder, return to work,
or even readjust their life-styles. Some patients actually deteriorate socially and psychologically, may become depressed, and may even attempt or commit
suicide 19-111. On reflection, this should not be surprising. Patients who have a chronic disability have
adapted their lives to this hopeless situation. On suddenly being “cured” of the seizures, they cannot overcome the lifetime of missed opportunities. Worse, this
cure can threaten all of their interpersonal relationships which have been built on being disabled. Thus,
the results of epilepsy surgery on seizure control, quality of life, and functional capacity are not uniformly
good.
In designing a prospective, randomized clinical trial
to evaluate surgical versus medical treatment there are
a number of key points to consider. The medical intractability of epilepsy in most patients entering an
epilepsy center is based on results (not always documented) obtained during years of medical management
by various physicians who are not epileptologists.
Rarely have the AEDs been systemically administered
to near clinical toxicity, singly or in combination. And
rarely have more than a few AEDs been tried. When
the AEDs are systematically manipulated in experimental trials, as many as a third of the patients will
experience improved seizure control. In fact, even
placebo treatment can stop seizures for 3 months. This
suggests that patients who get good results from epilepsy
surgely (and who coincidentally must get intensive
medical management) might be the same patients who
could get better seizure control Sy just intensive medical
management at an epilepsy center! In fact, Taylor and
Falconer reached the same conclusion 20 years ago:
. . . since no controlled study has been performed
with random allocation of cases, the question exists as
to whether these benefits [of epilepsy surgery1 were
mediated by the operation or better organized medication, careful follow-up, and powerful persuasion.” { 12)
Counting seizures cannot be the only end point in
evaluating the medical or surgical management of patients with epilepsy. Epilepsy is more than recurring
seizures. Taylor identified three components to epilepsy: the disease, the illness, and the predicament.
“Although the predicament of the person being considered for surgical treatment might have come about
“
508
Annals of Neurology
Vol 25
No 5 May 1989
because of this epilepsy, relief of the epilepsy need
not necessarily relieve the predicament.” El 31. Consequently it is important to include in the postsurgical
state, and during the medical treatment, an assessment
of the quality of life for each patient.
To control for these and other variables, a clinical
trial must be prospective and randomized. The study
should include all patients who would normally be
identified as having medically intractable epilepsy and
who would be suitable for an evaluation for epilepsy
surgery. These patients should all go through a presurgical evaluation during which the type of epilepsy is
clearly defined. Because different types of epilepsy
have different prognoses (whether treated medically or
surgically) the study should be restricted to one type,
or large enough to perform a subanalysis on rhe different types. At this point, the patients will be randomized to either the recommended surgical treatment (say anterior temporal lobectomy) or a medical
treatment regimen during which they will receive the
aggressive and thorough medical care typical at an academic epilepsy center. Don’t forget that although the
“intention to treat” the patient surgically has been
fulfilled, these patients are also receiving AEDs. Patients treated surgically and medically should be followed for an equal period of time to assess seizure
control and quality of life. At the end of the study,
patients in whom medical management failed would be
offered epilepsy surgery.
It will be argued that there are significant roadblocks
to performing such a study. It is technically difficult
and would require more patients than most single
epilepsy centers could handle. On the other hand, a
multicenter study is unlikely because of the wide variation in philosophy and resources at the major centers.
The cost of such a study will be substantial, and the
perceived need to answer the question may not be
sufficient to justify funding. However, the greatest
challenge is to convince physicians and grant reviewers
that the results of the study will not mean the end of
epilepsy surgery-only a redefinition of what epilepsy
surgery is, and what it actually does for the patient.
References
1. Engel J Jr, ed. Surgical treatment of the epilepsies. New York
Raven, 1987
2. Schmidt D, Einicke I, Haenel F. The influence of seizure type on
the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine. Arch Neurol 1986;43:263-265
3. Rodin EA. The prognosis of patients with epilepsy. Springfield,
I L Thomas, 1968
4. Elwes RDS, Johnson AL, Shorvon SD, Reynolds EH. The prognosis for seizure control in newly diagnosed epilepsy. N Engl J
Med 1984;311:944-947
5. Elwes RDC,Shorvon SD, Reynolds EH. Epileptics refractory to
anticonvulsants (letter). Neurology 1984;34:263
6. Rodin EA. Epileptics refractory to anticonvulsants (letter). Neurology 1984;34:263-264
7. Augustine EA, Novelly RA,Mattson RH, et al. Occupational
adjustment following neurosurgical treatment of epilepsy. Ann
Neurol 1984;15:68-72
8. van Buren JM, Ajmone-Marsan C, Mutsuga N, Sadowsky D.
Surgery of temporal lobe epilepsy. In Purpura DP, Penry JK,
Walter RD, eds. Neurosurgical Management of the Epilepsies.
Advances in Neurology Series, vol 8. New York: Raven,
1975: 155- 196
9. Engel J Jr. Outcome with respect to epileptic seizures. In: Engel
J Jr, ed. Surgical Treatment of the Epilepsies. New York: Raven, 1987:553-572
10. Horwitz MJ, Cohen FM. Temporal lobe epilepsy. Effect of
lobectomy on psychological functioning. Epilepsia 1968;9:2341
11. Taylor DC, Marsh SM. Implications of long-term follow-up
studies in epilepsy: with a note on the cause of death. In: Penry
JK, ed. Epilepsy, The Eighth International Symposium. New
York Raven, 1977:27-34
12. Taylor DC, Falconer MA. Clinical, socio-economic, and psychological changes after temporal lobectomy for epilepsy. Br J Psychiatry 1968;114:1247-126 1
13. Taylor DC. Psychiatric and social issues in measuring the input
and outcome of epilepsy surgery. In: Engel J Jr, ed. Surgical
Treatment of the Epilepsies. New York: Raven, 1987:485-503
14. Dodrill CB, Ojemann RJ, Wilkus AGA, et al. Multidisciplinary
prediction of seizure relief from cortical resection surgery. Ann
Neurol 1986;20:2-12
15. k e b JP, Engel J Jr, Babb TL. Interhemispheric propagation time
of human hippocampal seizures. I. Relationship to surgical outcome. Epilepsia 1986;27:286-293
16. King DW, Flanigin HF, Gallagher BB, et al. Temporal lobectomy for partial complex seizures: evaluation, results, and 1-year
follow-up. Neurology 1986;36: 334-339
17. Williamson PD, Spencer DD, Spencer SS, et al. Complex partial
seizures of frontal lobe origin. Ann Neurol 1985;18:497-504
18. Brey R, Laxer KD. Type VII complex partial seizures: no correlation with surgical outcome. Epilepsia 1985;26:657-660
19. Wieser HG. Electroclinical Features of the Psychomotor Seizure. Boston: Butterworths, 1983
20. Hardiman 0, Burke T, Phillips J, et al. Microdysgenesis in resected temporal neocortex: incidence and clinical significance in
focal epilepsy. Neurology 1988;38:1041-1047
21. Talairach Bancaud J, Szikla G, et al. Approche nouvelle de la
neurochirurgie de I'kpilepsie. Neurochirurgie 1974; 2O(Suppl
1):l-240
22. Duncan JS, Sager HJ. Seizure characteristics, pathology, and
outcome after temporal lobectomy. Neurology 1987;37:405409
23. Rasmussen T. Surgery of frontal lobe epilepsy. In Purpura DP,
Penry JK, Walter RD, eds. Neurosurgical Management of the
Epilepsies. Advances in Neurology Series, vol 8. New York:
Raven, 1975:197-206
24. Rasmussen T. Characteristics of a pure culture of frontal lobe
epilepsy. Epilepsia 1983;24:482-493
25. Rasmussen T. Surgery for epilepsy arising in regions other than
the temporal and frontal lobes. In: Purpura DP, Penry JK, Walter RD, eds. Neurosurgical Management of the Epilepsies. Advances in Neurology Series, vol 8. New York: Raven,
1975~207-226
26. Feindel W. Factors contributing to the success or failure of
surgical intervention for epilepsy. In: Purpura DP, Penry JK,
Walter RD, eds. Neurosurgical Management of the Epilepsies.
Advances in Neurology Series, vol 8. New York: Raven,
1975:281-298
27. Rasmussen TB. Surgical treatment of complex partial seizures:
results, lessons, and problems. Epilepsia 1983; 24(Suppl 1):
S65-S76
Reply
Roger J. Porter, MD,* and George J. Ojemann, M D t
The article by Dr Richard Dasheiff is provoLative and in
many ways quite correct. H e points out that better studies
are needed to evaluate the various aspects of surgery for
epilepsy and its consequences; the Epilepsy Branch of the
National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) is directly addressing this need
with the program announcement of January 8, 1988. Dr
Dasheiff presents rather dramatic data in his own table regarding the effectiveness of resective epilepsy surgery. It is
ironic, therefore, that he argues against the efficacy of such
surgical intervention. The artempt to downgrade the strikingly high percentage of seizure-free patients by noting that
they have an occasional simple partial seizure (aura) does a
major disservice to those who have moved from a world of
unpredictable alteration of consciousness to a world in which
they are able, at least on medical grounds, to live essentially
normal lives. Furthermore, the negative assertion that many
patients must continue to use medications to maintain a seizure-free state, while true and worthy of note, ignores the
dramatic benefit to these patients of being seizure free even
though medications may continue to be necessary.
A controlled clinical trial of resective surgery could be
ethically undertaken only if there were reason to believe that
the null hypothesis were true: that there was no difference
between seizure control with the best medical management
and with resective surgery. D r Dasheiff has presented the
data on the effectiveness of resective surgery. Some instructive information on the effectiveness of optimal medical
management in these patients are, in fact, available.
In 1977, the Epilepsy Branch, NINCDS, published a seminal study demonstrating the value of intensive monitoring in
23 patients with intractable epilepsy 111. Improvements in
seizure control were striking, but none of the patients with
partial seizures remained seizure free, even though, t o optimize the medical regimen, the duration of continuous hospitalization averaged 2 months. Since that time, a surgical
program has been developed at the National Institutes of
Health, and seizure-free patients have become commonplace; many of these patients have been followed for years
and have remained seizure free.
At the University of Washington Epilepsy Center, Drs
Carl Dodrill and Linda Ojemann have just completed the
first stage of a 5-year NINCDS-sponsored retrospective
evaluation of resective surgery, 5 and 10 years after the operation [2]. That study includes a matched control group, patients who had similar partial seizures with epileptic foci, who
were followed in the same epilepsy center over the same
time period, and who for one reason or another did not
undergo surgery. Only 1 of the first 23 control patients had
been seizure free for as long as 2 years in the 5 years (1 1
patients) or 10 years (12 patients) that they had been followed with the best medical management that the center
could provide. In fact, these patients were only relative control subjects for the surgical group, as the medical control
subjects had less severe seizure disorders than the surgical
patients. These data indicate that few patients considered for
resective surgery become seizure free, even with the very
best medical management.
Issues in Clinical Neuroscience: Dasheiff: Epilepsy Surgery 509
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