Epilepsy Surgery in the United States Analysis of Data From the National Association of Epilepsy Centers.
Content
Epilepsy Research 116 (2015) 105–109
Contents lists available at www.sciencedirect.com
Epilepsy Research
journal homepage: www.elsevier.com/locate/epilepsyres
Epilepsy surgery in the United States: Analysis of data from the
National Association of Epilepsy Centers
Kitti Kaiboriboon a,b,1 , Ayham M. Malkhachroum a , Ahmad Zrik a , Ahmad Daif a ,
Nicholas M. Schiltz c,d , David M. Labiner e , Samden D. Lhatoo a,∗
a
Epilepsy Center, Department of Neurology, University Hospitals Case Medical Center, Cleveland, OH, United States
Neurological and Behavioral Outcome Center, Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH, United States
c
Population Health and Outcomes Research Core, Clinical & Translational Science Collaborative, Department of Epidemiology & Biostatistics,
Case Western Reserve University, Cleveland, OH, United States
d
The Center for Child Health & Policy, Rainbow Babies and Children’s Hospital, Cleveland, OH, United States
e
Arizona Comprehensive Epilepsy Program, Department of Neurology, University of Arizona, Tucson, AZ, United States
b
a r t i c l e
i n f o
Article history:
Received 17 October 2014
Received in revised form 9 July 2015
Accepted 24 July 2015
Available online 26 July 2015
Keywords:
Epilepsy surgery
Refractory epilepsy
Temporal trends
a b s t r a c t
Objective: To examine trends in epilepsy-related surgical procedures performed at major epilepsy centers
in the US between 2003 and 2012, and in the service provision infrastructure of epilepsy centers over the
same time period.
Methods: We analyzed data from the National Association of Epilepsy Centers’ (NAEC) annual surveys. The
total annual figures, annual average figures per center and annual rates of each surgical procedure based
on US population numbers for that year were calculated. Additional information on center infrastructure
and manpower was also examined.
Results: The number of the NAEC’s level 3 and level 4 epilepsy centers submitting annual survey reports
increased from 37 centers in 2003 to 189 centers in 2012. The average reported number of Epilepsy
Monitoring Unit (EMU) beds per center increased from 7 beds in 2008 to 8 beds in 2012. Overall annual
EMU admission rates doubled between 2008 and 2012 but the average number of EMU admissions
and epilepsy surgeries performed per center declined over the same period. The annual rate of anterior
temporal lobectomies (ATL) for mesial temporal sclerosis (MTS) declined by >65% between 2006 and
2010. The annual rate of extratemporal surgery exceeded that of ATL for MTS from 2008 onwards, doubled
between 2007 and 2012 and comprised 38% of all resective surgeries in 2012. Vagus nerve stimulator
implant rates consistently increased year on year and exceeded resective surgeries in 2011 and 2012.
Conclusion: The last decade has seen a major change in the US epilepsy surgery landscape. Temporal lobectomies, particularly for MTS, have declined despite an increase in EMU admissions. On the other hands,
case complexity correspondingly increased as evidenced by more extratemporal surgery, intracranial
recordings and palliative procedures.
© 2015 Elsevier B.V. All rights reserved.
Introduction
The benefit of epilepsy surgery, particularly temporal lobectomy
has been well documented (Wiebe et al., 2001; Engel et al., 2012)
Abbreviations: AAN, American Academy of Neurology; ATL, anterior temporal
lobectomy; EMU, epilepsy monitoring Unit; MTLE, mesial temporal lobe epilepsy;
MTS, mesial temporal sclerosis; NAEC, National Association of Epilepsy Centers; NIS,
Nationwide Inpatient Sample; VNS, vagus nerve stimulation.
∗ Corresponding author. Tel.: +1 216 844 5855; fax: +1 216 844 3160.
E-mail address: [email protected] (S.D. Lhatoo).
1
Currently at Epilepsy Center, Swedish Neuroscience Institute, Seattle, WA, USA.
http://dx.doi.org/10.1016/j.eplepsyres.2015.07.007
0920-1211/© 2015 Elsevier B.V. All rights reserved.
and published estimates have emphasized the under-utilization of
this important treatment option (Lhatoo et al., 2003; Berg et al.,
2009). However, rather than the expected increase in surgical numbers effected by the impact of peer reviewed literature (Wiebe et al.,
2001), physician education and the establishment of guidelines and
practice parameters (Engel et al., 2003), surveys in the UK (Neligan
et al., 2013) and Sweden (Kumlien and Mattsson, 2010) suggest that
the number of resective surgeries have in fact declined over the past
decade. Recent studies in the US analyzing the Nationwide Inpatient Sample (NIS) also suggest similar trends (Englot et al., 2012;
Schiltz et al., 2013). Nonetheless, there is concern about the limited
accuracy and interpretability of the NIS data, which have mainly
relied on the International Classification of Diseases 9th Revision
106
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Clinical Modification (ICD-9-CM) codes (Kaiboriboon et al., 2011;
Cardenas et al., 2014). In addition, identification of specific surgical
procedures (e.g., temporal lobectomy, or extratemporal resection)
is impossible to carry out using the NIS dataset. Hence, the true
picture of epilepsy surgery volumes and time trends in the US,
particularly for temporal lobectomy, remains largely unknown. A
recent Q-PULSE survey of US epileptologists, assumed to be mostly
representing academic medical centers, has shown a broad, but not
universal, perception that there is an overall increase in case complexity and fewer cases of mesial temporal lobe epilepsy over the
past 10 years (Carlson, 2013). This article provides direct evidence
of epilepsy surgery expansion or lack thereof, in the US between
2003 and 2012 using data from the National Association of Epilepsy
Centers (NAEC).
Material and methods
The NAEC is a non-profit organization that has more than 190
members across the US (National Association of Epilepsy Centers,
2007). Every year the NAEC asks its members to provide information on the level of care that they provide including epilepsy surgery
volumes, and to indicate whether their epilepsy center meets criteria for level 3 or level 4 epilepsy center designations (Labiner et al.,
2010).
The NAEC’s level 3 epilepsy centers provide basic diagnostic
and treatment for patients with refractory epilepsy including noninvasive evaluations for epilepsy surgery, straightforward resective
epilepsy surgery (e.g., lesionectomy, anterior temporal lobectomy
in a clear-cut mesial temporal sclerosis (MTS)), and implantation
of devices such as vagus nerve stimulators (VNS). Level 4 epilepsy
centers serve as regional and/or national referral facilities and
therefore provide more complex diagnostic and treatment facilities including intracranial electrode placement, functional cortical
mapping, evoked potential recording, electrocorticography (ECoG),
and a broad range of surgical procedures for epilepsy (Labiner et al.,
2010).
The NAEC’s annual designation survey is based on the NAEC’s
guidelines for essential services, personnel, and facilities in specialized epilepsy centers (Labiner et al., 2010). Over time, there have
been several modifications to the annual survey.
We analyzed total as well as annual averaged figures per center for essential services, personnel, facilities and procedures. We
also calculated annual rates of EMU admissions and surgical procedures. Since US population numbers have increased over the study
period as has membership of the NAEC, we estimated annual surgical numbers based on the prevalent population with epilepsy in the
US. We used yearly data from the US Census population estimates
(US Census Bureau, 2011) and the previously published prevalence
rate of 7.1/1000 persons (Hirtz et al., 2007) to calculate the total
number of persons with epilepsy in the US for each year of our
study period.
We estimated the number of people with refractory epilepsy
to be about 30% of the entire epilepsy population (Kwan and
Sander, 2004). Since up to 20% of persons with refractory epilepsy
turn out to have non-epileptic seizures (Binnie et al., 1981), only
80% of the total number of persons with refractory epilepsy was
used as a denominator to calculate rates for comparison over
time. Mann–Kendall trend test was used to test for changes in
the rates of surgeries. Since multiple comparisons could lead to
false positive findings, false discovery rate control was performed
using Benjamini–Hochberg procedure (Benjamini and Hochberg,
1995). Statistical analysis was conducted using R version 2.15.1 for
Windows. All P-values were two-sided and values of <0.05 were
considered statistically significant.
Results
The number of epilepsy centers that responded to the survey
increased from 37 centers in 2003 to 189 centers in 2012. Table 1
shows the average annual expansion of Epilepsy Center facilities
over time. The number of epilepsy monitoring unit (EMU) beds
increased from approximately 7 beds in 2008 to approximately 8
in 2012. Average personnel numbers including those of epileptologists, neurosurgeons, neuropsychologists, and nurses all increased.
In 2012, each epilepsy center had approximately 5 epileptologists,
2 neurosurgeons, 1–2 neuropsychologists, and 3 nurses. In contrast,
the average number of EMU admissions and every epilepsy surgery
category per center declined over the years (Table 1).
Table 2 shows the rates of EMU admissions and epilepsy-related
surgical procedures calculated per 100,000 persons with refractory
epilepsy for each calendar year. Adjusting for changes in population numbers over the years, there was an overall increase in
EMU admission and intracranial monitoring rates. Rates of both
temporal and extratemporal resections also increased to reach
a peak in 2009, approximately 6 years after the publication of
practice guidelines for epilepsy surgery referrals by the American Academy of Neurology (AAN) (Engel et al., 2003), and then
declined thereafter. The rates of ATL for MTS, and non-lesional
temporal lobectomy rose and dropped much earlier. In 2010, the
rates of ATL for MTS and non-lesional resection were less than
half of those in 2006. Temporal lobectomy rates continued to
decline over the last few survey years, but rates of extratemporal
Table 1
Averaged annual numbers of essential services, personnel, facilities and procedures per epilepsy center.
Number of epilepsy centers
EMU beds
EMU admission
Epileptologists
Neurosurgeons
Neuropsychologists
Nurses
Intracranial EEG recording
Temporal lobe resection
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
37
–
–
3.70
1.70
0.16
0.62
28.84
–
–
–
–
26.30
–
–
55
–
–
3.58
0.95
0.45
0.64
7.96
–
–
–
–
8.93
–
–
72
–
–
3.64
1.76
1.35
1.17
15.42
–
–
–
–
18.72
–
–
84
–
–
3.89
1.73
1.32
1.15
18.90
–
–
–
–
–
–
–
87
6.82
–
4.80
1.90
1.44
1.91
14.78
–
5.33
–
–
–
–
–
98
6.38
387.17
4.87
1.88
1.52
2.59
12.21
18.64
7.44
1.20
1.44
17.56
2.92
0.77
117
7.11
425.32
4.98
2.04
1.52
1.89
12.26
17.54
8.14
1.33
1.26
17.34
4.21
1.18
129
6.26
418.13
5.01
2.10
1.47
1.93
10.80
14.70
7.26
1.11
1.23
19.27
3.71
0.53
163
7.31
403.88
4.96
1.87
1.45
1.76
8.22
8.75
5.61
–
1.10
16.67
–
0.41
189
7.71
363.33
5.10
1.88
1.43
2.72
8.17
8.10
5.11
–
1.01
14.86
–
0.22
Abbreviations: EMU, epilepsy monitoring unit; EEG, electroencephalography; VNS, vagus nerve stimulation; NB. Blank boxes indicate that data was not collected for these
categories.
Table 2
Estimates of the annual rates of epilepsy surgical procedures (per 100,000 persons with refractory epilepsy) between 2003 and 2012.
2004
2005
2006
2007
2008
2009
2010
2011
2012
S statisticc
2903.26
4.95
–
215.68
–
–
132.60
101.67
–
–
–
–
196.68
–
–
2930.46
4.99
–
87.71
346.85
–
106.14
113.35
–
–
–
–
98.33
–
–
2957.53
5.04
–
220.25
349.03
–
218.87
154.18
–
–
–
–
267.48
–
–
2985.93
5.09
–
312.11
394.65
–
–
314.46
125.39
–
–
–
–
–
–
3015.80
5.14
–
250.25
506.14
–
–
149.84
–
90.29
–
–
–
–
–
3043.75
5.19
7315.66
230.79
542.75
352.26
227.90
101.03
46.47
140.56
22.75
27.19
331.82
55.14
14.46
3070.07
5.23
9512.19
274.31
632.15
392.25
291.89
135.15
70.92
181.98
29.82
28.10
387.85
94.24
26.38
3093.26
5.27
10,233.32
264.28
594.77
359.71
228.80
110.23
48.38
177.77
27.13
30.17
471.64
90.69
13.09
3115.88
5.31
12,399.20
252.38
–
268.77
–
–
–
172.33
–
33.71
511.73
–
12.62
3139.14
5.35
12,837.50
288.83
–
286.03
–
–
–
180.40
–
35.52
525.14
–
7.85
–
–
10
23
19
–4
11
–2
–d
7
–d
10
26
–d
–8
AdjustedPvalue
–
–
0.08
0.11
0.04
0.56
0.11
0.90
–d
0.36
–d
0.08
0.02
–d
0.14
Adjusted P-values are from the Mann–Kendall non-parametric test for trend, and corrected for multiple comparisons using the Benjamini–Hochberg method. Abbreviations: EMU, epilepsy monitoring unit; ATL, anterior temporal
lobectomy; MTS, mesial temporal sclerosis; VNS, vagus nerve stimulation; NB: Blank boxes indicate that data was not collected for these categories.
a
Population (per 100,000) is the total US population based on data from the US Census Bureau (2011).
b
Persons with refractory epilepsy (per 100,000) was estimated based on 7.1/1000 prevalence rate for the general US population (Hirtz et al., 2007).
c
Kendall’s S statistic.
d
S statistic and P-value cannot be obtained due to too few data points.
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Populationa
Persons with refractory epilepsyb
EMU Admission
Intracranial EEG recording
Total number of surgeries
Temporal lobe resection
ATL
ATL with MTS
Non-lesional
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
107
108
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Table 3
Essential services, personnel, facilities and surgical procedures in adult and pediatric specialized epilepsy centers.
Adult epilepsy centers
Number of epilepsy centers
EMU beds
EMU admission
Epileptologists
Neurosurgeons
Neuropsychologists
Nurses
Intracranial EEG recording
Temporal lobe resection
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
2008
14
–
–
35
17
3
8
501
–
–
–
–
400
–
–
29
149
9836
113
54
40
71
687
685
438
94
117
789
114
13
Pediatric epilepsy centers
2012
66
349
13,160
248
100
85
144
530
534
234
–
14
714
–
15
2003
3
–
–
13
9
–
–
34
–
–
–
–
154
–
–
Unspecified/combined
2008
2012
2003
10
72
4922
58
25
18
36
200
134
125
37
48
220
25
3
28
238
15,290
142
68
41
97
293
164
287
–
104
549
–
6
20
–
–
89
37
3
15
532
–
–
–
–
419
–
–
2008
59
404
23,185
306
105
91
147
710
1276
416
61
72
1152
197
65
2012
95
870
40,219
574
187
144
274
722
832
444
–
72
1546
–
21
Abbreviations: EMU, epilepsy monitoring unit; EEG, electroencephalography; VNS, vagus nerve stimulation; NB: Blank boxes indicate that data was not collected for these
categories.
resection remained relatively stable. Interestingly, corpus callosotomy, and VNS implants were the only procedures that were
performed at steadily increasing rates. Table 3 shows absolute
numbers of center infrastructure and surgical procedures according
to adult, pediatric or combined/unspecified centers at the beginning, midpoint and end of the studied period.
Discussion
This study provides direct evidence from major epilepsy centers in the US to suggest that surgical candidates are now mostly
complex epilepsy cases, rather than straightforward temporal
lobectomies. This is evidenced by an increase in rates of extratemporal surgery, intracranial EEG recordings, corpus callosotomy
and VNS implants and a slight decrease in temporal lobectomies.
Limitations inherent to the NAEC survey data should be considered while interpreting the findings of the current analysis. Changes
in survey questions over the years prevent consistency and a more
complete picture in some measures. Self-reporting of surgical volumes without independent validation can undoubtedly result in
over-estimation, even though the NAEC has stopped using the volume of surgical procedures to designate level of epilepsy centers
since 2010 (Labiner et al., 2010). It is therefore undeniable that data
from the NAEC could be imprecise although it is relatively unlikely
that self-reported numbers would exaggerate declining numbers.
Nonetheless, our findings are in line with previous reports that have
used different datasets (Englot et al., 2012; Schiltz et al., 2013). Until
other alternative data sources are available, the NAEC’s annual survey is the only and the most comprehensive data source that can
be used to assess the epilepsy surgery landscape in the US.
Although our analysis did not include non-NAEC centers, a previous study has shown that the majority of epilepsy surgeries are
performed in urban teaching hospitals (Schiltz et al., 2013), most
of which are likely to be the NAEC members and non-member hospitals are not likely to perform surgeries in large volumes.
Two recent studies of epilepsy surgery utilization in the US
using NIS data, together spanning from 1990 to 2009, reported
two important findings, first that epilepsy surgery numbers have
not increased as expected over time (Englot et al., 2012; Schiltz
et al., 2013); and second, that smaller, non-teaching hospitals have
seen a significant increase in the numbers of pre-surgical assessment (Schiltz et al., 2013). Our finding of an early increase in
surgeries between 2003 and 2009 suggests that US neurologists are
likely to have substantially adopted practice guidelines for epilepsy
surgery referrals by the AAN (Engel et al., 2003). In support of this
contention, a recent survey showed that 82% of neurologists have
actually referred patients for epilepsy surgery (Hakimi et al., 2008).
High proportion of intracranial EEG recordings compared to the
number of resective surgery in early years (between 2003 and
2006) could be due to the fact that there were not many NAEC’s
epilepsy centers during that time. The existing centers were mostly
large reputable academic centers that received referral of complex
epilepsy cases. The proportion of intracranial EEG recordings and
the number of resective surgery has remained quite stable from
2007 onward.
A decrease in the number of temporal lobectomies, particularly
ATL for MTS, in adult epilepsy centers over the past few years has
been noticed in other countries including the UK (Neligan et al.,
2013) and Sweden (Kumlien and Mattsson, 2010). We found that
the annual rate of ATL for MTS declined by more than 65% between
2006 and 2010, which closely mirrors these reports and the anecdotal experiences of many US centers.
Reasons for the decline in ATL for MTS are mainly speculative.
Importantly, although MTS is largely considered synonymous with
intractability, its natural history remains unknown (Berg, 2008).
Surgical literature often shows a significant delay of 20 years or
more from the onset of mesial temporal lobe epilepsy (MTLE) to
resective surgery (Berg, 2004). The introduction of several new
antiepileptic medications over the last two decades may prolong
time to surgery as some patients and/or physicians adopt the conservative approach of trying new drugs and thus delaying surgery.
Some patients may enter varying periods of remission before eventual relapse (Neligan et al., 2012). Given a protracted process of
intractability (Berg et al., 2006) and delay to surgery, it is reasonable
to assume that the prevalent pool of surgical candidates (particularly MTLE) has probably been efficiently dealt with by the rapid
emergence and activity of epilepsy centers in the past decade. Since
annual incident numbers of surgical candidates are likely to be
much smaller (Lhatoo et al., 2003), the decline in surgical numbers
is not surprising.
Neligan et al. (2013) posit that if the reduction of prevalent surgical cases is a major factor in the decline in temporal lobectomy
numbers, there should be an increase in the number of surgical
candidates with fairly short epilepsy durations. This logic can only
hold true if the concept of early surgery for epilepsy has been
effectively embraced. To date, no study has shown a reduction in
epilepsy duration prior to surgery (Bien et al., 2013; Rydenhag et al.,
2013). In addition, the Early Randomized Surgical Epilepsy Trial
(ERSET), which was designed to evaluate the efficacy of surgery
in patients with less than 2 years of disabling MTLE, recruited
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
relatively small numbers to either arm (Engel et al., 2012). Further
studies that examine more recent data (from 2010 or 2011 onward)
will likely provide better insight into the duration of epilepsy prior
to surgery but it in light of the evidence as detailed, it seems likely
that the decline in prevalent pool numbers through increased numbers of epilepsy centers and surgeries, is primarily responsible for
the overall decline in annual surgery numbers.
Other factors that may play a role but are as yet relatively
unsubstantiated are an improved prognosis of refractory epilepsy
in the modern AED era (Luciano and Shorvon, 2007), improved
management of complex febrile seizures and febrile status epilepticus resulting in fewer cases of subsequent MTS and MTLE, lower
incidence or improved treatment of MTS-causing brain infections
such as bacterial meningitis and viral encephalitis in the modern
antibiotic era, and successful surgical treatment of intractable focal
childhood epilepsies. A subgroup analysis of clearly identified pediatric epilepsy centers revealed an increase in pediatric epilepsy
surgeries for both temporal and extratemporal lobe epilepsies
(Table 3). An expansion of pediatric epilepsy expertise (Pestana
Knight et al., 2015) is therefore likely to contribute, at least in part to
the apparently lower number of resections, particularly temporal
lobectomies, in adults.
A significant increase in palliative procedures, particularly
VNS treatment is intriguing. Data from international collaborative
surgery surveys suggest that there are more VNS operations performed in the US than in Europe and Australia combined (Harvey
et al., 2008). A recent analysis of VNS use in the US shows an increase
in the number of VNS operations between 1998 and 2003, followed
by a slight drop in 2004 and 2005 (Baaj et al., 2008). In contrast,
although NAEC data confirms this drop in VNS implantation in
2004, there have been dramatic increases subsequently. In 2010,
NAEC data suggests that VNS became the most common epilepsyrelated surgical procedure performed in the US, surpassing the
number of temporal and extratemporal lobe resections combined
in 2011 as well as 2012. The utilization of VNS over all resective
surgeries has been confirmed in the UK (Neligan et al., 2013) and
worldwide, more than 99.5% of VNS implants in 2011 and 2012
were for epilepsy (Personal Communication: Cyberonics, Finance
Department. Aug 2013—http://ir.cyberonics.com/results.cfm). The
apparent explosion in VNS usage, an expensive and mildly palliative
rather than curative option, and which does not replace medication,
is intriguing and requires scrutiny that is beyond the scope of this
data.
Conclusion
There appears to be a disconnect between projected numbers of
epilepsy surgery candidates in the US and current annual rates of
surgery despite an expansion in epilepsy centers and center infrastructure. This is likely to have significant implications in healthcare
resource planning. The precise factors that underpin this are currently speculative but certainly merit further study. Efforts focusing
on the mechanisms responsible for the development and evolution of drug resistant epilepsy, and on more effective treatments
than those currently available for patients who are not surgical
candidates and/or those who fail surgery are more important than
ever.
Acknowledgements
The authors would like to sincerely thank the National Association of Epilepsy Centers for sharing and allowing analysis of their
data. Drs. Kaiboriboon and Lhatoo received support from the Centers for Disease Control and Prevention (Grant no. 3U48DP001930).
109
Dr. Lhatoo received support from the National Institute of Neurological Disorders and Stroke (Grant no. P20NS076965).
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Contents lists available at www.sciencedirect.com
Epilepsy Research
journal homepage: www.elsevier.com/locate/epilepsyres
Epilepsy surgery in the United States: Analysis of data from the
National Association of Epilepsy Centers
Kitti Kaiboriboon a,b,1 , Ayham M. Malkhachroum a , Ahmad Zrik a , Ahmad Daif a ,
Nicholas M. Schiltz c,d , David M. Labiner e , Samden D. Lhatoo a,∗
a
Epilepsy Center, Department of Neurology, University Hospitals Case Medical Center, Cleveland, OH, United States
Neurological and Behavioral Outcome Center, Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH, United States
c
Population Health and Outcomes Research Core, Clinical & Translational Science Collaborative, Department of Epidemiology & Biostatistics,
Case Western Reserve University, Cleveland, OH, United States
d
The Center for Child Health & Policy, Rainbow Babies and Children’s Hospital, Cleveland, OH, United States
e
Arizona Comprehensive Epilepsy Program, Department of Neurology, University of Arizona, Tucson, AZ, United States
b
a r t i c l e
i n f o
Article history:
Received 17 October 2014
Received in revised form 9 July 2015
Accepted 24 July 2015
Available online 26 July 2015
Keywords:
Epilepsy surgery
Refractory epilepsy
Temporal trends
a b s t r a c t
Objective: To examine trends in epilepsy-related surgical procedures performed at major epilepsy centers
in the US between 2003 and 2012, and in the service provision infrastructure of epilepsy centers over the
same time period.
Methods: We analyzed data from the National Association of Epilepsy Centers’ (NAEC) annual surveys. The
total annual figures, annual average figures per center and annual rates of each surgical procedure based
on US population numbers for that year were calculated. Additional information on center infrastructure
and manpower was also examined.
Results: The number of the NAEC’s level 3 and level 4 epilepsy centers submitting annual survey reports
increased from 37 centers in 2003 to 189 centers in 2012. The average reported number of Epilepsy
Monitoring Unit (EMU) beds per center increased from 7 beds in 2008 to 8 beds in 2012. Overall annual
EMU admission rates doubled between 2008 and 2012 but the average number of EMU admissions
and epilepsy surgeries performed per center declined over the same period. The annual rate of anterior
temporal lobectomies (ATL) for mesial temporal sclerosis (MTS) declined by >65% between 2006 and
2010. The annual rate of extratemporal surgery exceeded that of ATL for MTS from 2008 onwards, doubled
between 2007 and 2012 and comprised 38% of all resective surgeries in 2012. Vagus nerve stimulator
implant rates consistently increased year on year and exceeded resective surgeries in 2011 and 2012.
Conclusion: The last decade has seen a major change in the US epilepsy surgery landscape. Temporal lobectomies, particularly for MTS, have declined despite an increase in EMU admissions. On the other hands,
case complexity correspondingly increased as evidenced by more extratemporal surgery, intracranial
recordings and palliative procedures.
© 2015 Elsevier B.V. All rights reserved.
Introduction
The benefit of epilepsy surgery, particularly temporal lobectomy
has been well documented (Wiebe et al., 2001; Engel et al., 2012)
Abbreviations: AAN, American Academy of Neurology; ATL, anterior temporal
lobectomy; EMU, epilepsy monitoring Unit; MTLE, mesial temporal lobe epilepsy;
MTS, mesial temporal sclerosis; NAEC, National Association of Epilepsy Centers; NIS,
Nationwide Inpatient Sample; VNS, vagus nerve stimulation.
∗ Corresponding author. Tel.: +1 216 844 5855; fax: +1 216 844 3160.
E-mail address: [email protected] (S.D. Lhatoo).
1
Currently at Epilepsy Center, Swedish Neuroscience Institute, Seattle, WA, USA.
http://dx.doi.org/10.1016/j.eplepsyres.2015.07.007
0920-1211/© 2015 Elsevier B.V. All rights reserved.
and published estimates have emphasized the under-utilization of
this important treatment option (Lhatoo et al., 2003; Berg et al.,
2009). However, rather than the expected increase in surgical numbers effected by the impact of peer reviewed literature (Wiebe et al.,
2001), physician education and the establishment of guidelines and
practice parameters (Engel et al., 2003), surveys in the UK (Neligan
et al., 2013) and Sweden (Kumlien and Mattsson, 2010) suggest that
the number of resective surgeries have in fact declined over the past
decade. Recent studies in the US analyzing the Nationwide Inpatient Sample (NIS) also suggest similar trends (Englot et al., 2012;
Schiltz et al., 2013). Nonetheless, there is concern about the limited
accuracy and interpretability of the NIS data, which have mainly
relied on the International Classification of Diseases 9th Revision
106
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Clinical Modification (ICD-9-CM) codes (Kaiboriboon et al., 2011;
Cardenas et al., 2014). In addition, identification of specific surgical
procedures (e.g., temporal lobectomy, or extratemporal resection)
is impossible to carry out using the NIS dataset. Hence, the true
picture of epilepsy surgery volumes and time trends in the US,
particularly for temporal lobectomy, remains largely unknown. A
recent Q-PULSE survey of US epileptologists, assumed to be mostly
representing academic medical centers, has shown a broad, but not
universal, perception that there is an overall increase in case complexity and fewer cases of mesial temporal lobe epilepsy over the
past 10 years (Carlson, 2013). This article provides direct evidence
of epilepsy surgery expansion or lack thereof, in the US between
2003 and 2012 using data from the National Association of Epilepsy
Centers (NAEC).
Material and methods
The NAEC is a non-profit organization that has more than 190
members across the US (National Association of Epilepsy Centers,
2007). Every year the NAEC asks its members to provide information on the level of care that they provide including epilepsy surgery
volumes, and to indicate whether their epilepsy center meets criteria for level 3 or level 4 epilepsy center designations (Labiner et al.,
2010).
The NAEC’s level 3 epilepsy centers provide basic diagnostic
and treatment for patients with refractory epilepsy including noninvasive evaluations for epilepsy surgery, straightforward resective
epilepsy surgery (e.g., lesionectomy, anterior temporal lobectomy
in a clear-cut mesial temporal sclerosis (MTS)), and implantation
of devices such as vagus nerve stimulators (VNS). Level 4 epilepsy
centers serve as regional and/or national referral facilities and
therefore provide more complex diagnostic and treatment facilities including intracranial electrode placement, functional cortical
mapping, evoked potential recording, electrocorticography (ECoG),
and a broad range of surgical procedures for epilepsy (Labiner et al.,
2010).
The NAEC’s annual designation survey is based on the NAEC’s
guidelines for essential services, personnel, and facilities in specialized epilepsy centers (Labiner et al., 2010). Over time, there have
been several modifications to the annual survey.
We analyzed total as well as annual averaged figures per center for essential services, personnel, facilities and procedures. We
also calculated annual rates of EMU admissions and surgical procedures. Since US population numbers have increased over the study
period as has membership of the NAEC, we estimated annual surgical numbers based on the prevalent population with epilepsy in the
US. We used yearly data from the US Census population estimates
(US Census Bureau, 2011) and the previously published prevalence
rate of 7.1/1000 persons (Hirtz et al., 2007) to calculate the total
number of persons with epilepsy in the US for each year of our
study period.
We estimated the number of people with refractory epilepsy
to be about 30% of the entire epilepsy population (Kwan and
Sander, 2004). Since up to 20% of persons with refractory epilepsy
turn out to have non-epileptic seizures (Binnie et al., 1981), only
80% of the total number of persons with refractory epilepsy was
used as a denominator to calculate rates for comparison over
time. Mann–Kendall trend test was used to test for changes in
the rates of surgeries. Since multiple comparisons could lead to
false positive findings, false discovery rate control was performed
using Benjamini–Hochberg procedure (Benjamini and Hochberg,
1995). Statistical analysis was conducted using R version 2.15.1 for
Windows. All P-values were two-sided and values of <0.05 were
considered statistically significant.
Results
The number of epilepsy centers that responded to the survey
increased from 37 centers in 2003 to 189 centers in 2012. Table 1
shows the average annual expansion of Epilepsy Center facilities
over time. The number of epilepsy monitoring unit (EMU) beds
increased from approximately 7 beds in 2008 to approximately 8
in 2012. Average personnel numbers including those of epileptologists, neurosurgeons, neuropsychologists, and nurses all increased.
In 2012, each epilepsy center had approximately 5 epileptologists,
2 neurosurgeons, 1–2 neuropsychologists, and 3 nurses. In contrast,
the average number of EMU admissions and every epilepsy surgery
category per center declined over the years (Table 1).
Table 2 shows the rates of EMU admissions and epilepsy-related
surgical procedures calculated per 100,000 persons with refractory
epilepsy for each calendar year. Adjusting for changes in population numbers over the years, there was an overall increase in
EMU admission and intracranial monitoring rates. Rates of both
temporal and extratemporal resections also increased to reach
a peak in 2009, approximately 6 years after the publication of
practice guidelines for epilepsy surgery referrals by the American Academy of Neurology (AAN) (Engel et al., 2003), and then
declined thereafter. The rates of ATL for MTS, and non-lesional
temporal lobectomy rose and dropped much earlier. In 2010, the
rates of ATL for MTS and non-lesional resection were less than
half of those in 2006. Temporal lobectomy rates continued to
decline over the last few survey years, but rates of extratemporal
Table 1
Averaged annual numbers of essential services, personnel, facilities and procedures per epilepsy center.
Number of epilepsy centers
EMU beds
EMU admission
Epileptologists
Neurosurgeons
Neuropsychologists
Nurses
Intracranial EEG recording
Temporal lobe resection
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
37
–
–
3.70
1.70
0.16
0.62
28.84
–
–
–
–
26.30
–
–
55
–
–
3.58
0.95
0.45
0.64
7.96
–
–
–
–
8.93
–
–
72
–
–
3.64
1.76
1.35
1.17
15.42
–
–
–
–
18.72
–
–
84
–
–
3.89
1.73
1.32
1.15
18.90
–
–
–
–
–
–
–
87
6.82
–
4.80
1.90
1.44
1.91
14.78
–
5.33
–
–
–
–
–
98
6.38
387.17
4.87
1.88
1.52
2.59
12.21
18.64
7.44
1.20
1.44
17.56
2.92
0.77
117
7.11
425.32
4.98
2.04
1.52
1.89
12.26
17.54
8.14
1.33
1.26
17.34
4.21
1.18
129
6.26
418.13
5.01
2.10
1.47
1.93
10.80
14.70
7.26
1.11
1.23
19.27
3.71
0.53
163
7.31
403.88
4.96
1.87
1.45
1.76
8.22
8.75
5.61
–
1.10
16.67
–
0.41
189
7.71
363.33
5.10
1.88
1.43
2.72
8.17
8.10
5.11
–
1.01
14.86
–
0.22
Abbreviations: EMU, epilepsy monitoring unit; EEG, electroencephalography; VNS, vagus nerve stimulation; NB. Blank boxes indicate that data was not collected for these
categories.
Table 2
Estimates of the annual rates of epilepsy surgical procedures (per 100,000 persons with refractory epilepsy) between 2003 and 2012.
2004
2005
2006
2007
2008
2009
2010
2011
2012
S statisticc
2903.26
4.95
–
215.68
–
–
132.60
101.67
–
–
–
–
196.68
–
–
2930.46
4.99
–
87.71
346.85
–
106.14
113.35
–
–
–
–
98.33
–
–
2957.53
5.04
–
220.25
349.03
–
218.87
154.18
–
–
–
–
267.48
–
–
2985.93
5.09
–
312.11
394.65
–
–
314.46
125.39
–
–
–
–
–
–
3015.80
5.14
–
250.25
506.14
–
–
149.84
–
90.29
–
–
–
–
–
3043.75
5.19
7315.66
230.79
542.75
352.26
227.90
101.03
46.47
140.56
22.75
27.19
331.82
55.14
14.46
3070.07
5.23
9512.19
274.31
632.15
392.25
291.89
135.15
70.92
181.98
29.82
28.10
387.85
94.24
26.38
3093.26
5.27
10,233.32
264.28
594.77
359.71
228.80
110.23
48.38
177.77
27.13
30.17
471.64
90.69
13.09
3115.88
5.31
12,399.20
252.38
–
268.77
–
–
–
172.33
–
33.71
511.73
–
12.62
3139.14
5.35
12,837.50
288.83
–
286.03
–
–
–
180.40
–
35.52
525.14
–
7.85
–
–
10
23
19
–4
11
–2
–d
7
–d
10
26
–d
–8
AdjustedPvalue
–
–
0.08
0.11
0.04
0.56
0.11
0.90
–d
0.36
–d
0.08
0.02
–d
0.14
Adjusted P-values are from the Mann–Kendall non-parametric test for trend, and corrected for multiple comparisons using the Benjamini–Hochberg method. Abbreviations: EMU, epilepsy monitoring unit; ATL, anterior temporal
lobectomy; MTS, mesial temporal sclerosis; VNS, vagus nerve stimulation; NB: Blank boxes indicate that data was not collected for these categories.
a
Population (per 100,000) is the total US population based on data from the US Census Bureau (2011).
b
Persons with refractory epilepsy (per 100,000) was estimated based on 7.1/1000 prevalence rate for the general US population (Hirtz et al., 2007).
c
Kendall’s S statistic.
d
S statistic and P-value cannot be obtained due to too few data points.
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Populationa
Persons with refractory epilepsyb
EMU Admission
Intracranial EEG recording
Total number of surgeries
Temporal lobe resection
ATL
ATL with MTS
Non-lesional
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
107
108
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
Table 3
Essential services, personnel, facilities and surgical procedures in adult and pediatric specialized epilepsy centers.
Adult epilepsy centers
Number of epilepsy centers
EMU beds
EMU admission
Epileptologists
Neurosurgeons
Neuropsychologists
Nurses
Intracranial EEG recording
Temporal lobe resection
Extratemporal resection
Hemispherectomy
Corpus callosotomy
VNS
Neurostimulator implantation
Radiofrequency surgery
2003
2008
14
–
–
35
17
3
8
501
–
–
–
–
400
–
–
29
149
9836
113
54
40
71
687
685
438
94
117
789
114
13
Pediatric epilepsy centers
2012
66
349
13,160
248
100
85
144
530
534
234
–
14
714
–
15
2003
3
–
–
13
9
–
–
34
–
–
–
–
154
–
–
Unspecified/combined
2008
2012
2003
10
72
4922
58
25
18
36
200
134
125
37
48
220
25
3
28
238
15,290
142
68
41
97
293
164
287
–
104
549
–
6
20
–
–
89
37
3
15
532
–
–
–
–
419
–
–
2008
59
404
23,185
306
105
91
147
710
1276
416
61
72
1152
197
65
2012
95
870
40,219
574
187
144
274
722
832
444
–
72
1546
–
21
Abbreviations: EMU, epilepsy monitoring unit; EEG, electroencephalography; VNS, vagus nerve stimulation; NB: Blank boxes indicate that data was not collected for these
categories.
resection remained relatively stable. Interestingly, corpus callosotomy, and VNS implants were the only procedures that were
performed at steadily increasing rates. Table 3 shows absolute
numbers of center infrastructure and surgical procedures according
to adult, pediatric or combined/unspecified centers at the beginning, midpoint and end of the studied period.
Discussion
This study provides direct evidence from major epilepsy centers in the US to suggest that surgical candidates are now mostly
complex epilepsy cases, rather than straightforward temporal
lobectomies. This is evidenced by an increase in rates of extratemporal surgery, intracranial EEG recordings, corpus callosotomy
and VNS implants and a slight decrease in temporal lobectomies.
Limitations inherent to the NAEC survey data should be considered while interpreting the findings of the current analysis. Changes
in survey questions over the years prevent consistency and a more
complete picture in some measures. Self-reporting of surgical volumes without independent validation can undoubtedly result in
over-estimation, even though the NAEC has stopped using the volume of surgical procedures to designate level of epilepsy centers
since 2010 (Labiner et al., 2010). It is therefore undeniable that data
from the NAEC could be imprecise although it is relatively unlikely
that self-reported numbers would exaggerate declining numbers.
Nonetheless, our findings are in line with previous reports that have
used different datasets (Englot et al., 2012; Schiltz et al., 2013). Until
other alternative data sources are available, the NAEC’s annual survey is the only and the most comprehensive data source that can
be used to assess the epilepsy surgery landscape in the US.
Although our analysis did not include non-NAEC centers, a previous study has shown that the majority of epilepsy surgeries are
performed in urban teaching hospitals (Schiltz et al., 2013), most
of which are likely to be the NAEC members and non-member hospitals are not likely to perform surgeries in large volumes.
Two recent studies of epilepsy surgery utilization in the US
using NIS data, together spanning from 1990 to 2009, reported
two important findings, first that epilepsy surgery numbers have
not increased as expected over time (Englot et al., 2012; Schiltz
et al., 2013); and second, that smaller, non-teaching hospitals have
seen a significant increase in the numbers of pre-surgical assessment (Schiltz et al., 2013). Our finding of an early increase in
surgeries between 2003 and 2009 suggests that US neurologists are
likely to have substantially adopted practice guidelines for epilepsy
surgery referrals by the AAN (Engel et al., 2003). In support of this
contention, a recent survey showed that 82% of neurologists have
actually referred patients for epilepsy surgery (Hakimi et al., 2008).
High proportion of intracranial EEG recordings compared to the
number of resective surgery in early years (between 2003 and
2006) could be due to the fact that there were not many NAEC’s
epilepsy centers during that time. The existing centers were mostly
large reputable academic centers that received referral of complex
epilepsy cases. The proportion of intracranial EEG recordings and
the number of resective surgery has remained quite stable from
2007 onward.
A decrease in the number of temporal lobectomies, particularly
ATL for MTS, in adult epilepsy centers over the past few years has
been noticed in other countries including the UK (Neligan et al.,
2013) and Sweden (Kumlien and Mattsson, 2010). We found that
the annual rate of ATL for MTS declined by more than 65% between
2006 and 2010, which closely mirrors these reports and the anecdotal experiences of many US centers.
Reasons for the decline in ATL for MTS are mainly speculative.
Importantly, although MTS is largely considered synonymous with
intractability, its natural history remains unknown (Berg, 2008).
Surgical literature often shows a significant delay of 20 years or
more from the onset of mesial temporal lobe epilepsy (MTLE) to
resective surgery (Berg, 2004). The introduction of several new
antiepileptic medications over the last two decades may prolong
time to surgery as some patients and/or physicians adopt the conservative approach of trying new drugs and thus delaying surgery.
Some patients may enter varying periods of remission before eventual relapse (Neligan et al., 2012). Given a protracted process of
intractability (Berg et al., 2006) and delay to surgery, it is reasonable
to assume that the prevalent pool of surgical candidates (particularly MTLE) has probably been efficiently dealt with by the rapid
emergence and activity of epilepsy centers in the past decade. Since
annual incident numbers of surgical candidates are likely to be
much smaller (Lhatoo et al., 2003), the decline in surgical numbers
is not surprising.
Neligan et al. (2013) posit that if the reduction of prevalent surgical cases is a major factor in the decline in temporal lobectomy
numbers, there should be an increase in the number of surgical
candidates with fairly short epilepsy durations. This logic can only
hold true if the concept of early surgery for epilepsy has been
effectively embraced. To date, no study has shown a reduction in
epilepsy duration prior to surgery (Bien et al., 2013; Rydenhag et al.,
2013). In addition, the Early Randomized Surgical Epilepsy Trial
(ERSET), which was designed to evaluate the efficacy of surgery
in patients with less than 2 years of disabling MTLE, recruited
K. Kaiboriboon et al. / Epilepsy Research 116 (2015) 105–109
relatively small numbers to either arm (Engel et al., 2012). Further
studies that examine more recent data (from 2010 or 2011 onward)
will likely provide better insight into the duration of epilepsy prior
to surgery but it in light of the evidence as detailed, it seems likely
that the decline in prevalent pool numbers through increased numbers of epilepsy centers and surgeries, is primarily responsible for
the overall decline in annual surgery numbers.
Other factors that may play a role but are as yet relatively
unsubstantiated are an improved prognosis of refractory epilepsy
in the modern AED era (Luciano and Shorvon, 2007), improved
management of complex febrile seizures and febrile status epilepticus resulting in fewer cases of subsequent MTS and MTLE, lower
incidence or improved treatment of MTS-causing brain infections
such as bacterial meningitis and viral encephalitis in the modern
antibiotic era, and successful surgical treatment of intractable focal
childhood epilepsies. A subgroup analysis of clearly identified pediatric epilepsy centers revealed an increase in pediatric epilepsy
surgeries for both temporal and extratemporal lobe epilepsies
(Table 3). An expansion of pediatric epilepsy expertise (Pestana
Knight et al., 2015) is therefore likely to contribute, at least in part to
the apparently lower number of resections, particularly temporal
lobectomies, in adults.
A significant increase in palliative procedures, particularly
VNS treatment is intriguing. Data from international collaborative
surgery surveys suggest that there are more VNS operations performed in the US than in Europe and Australia combined (Harvey
et al., 2008). A recent analysis of VNS use in the US shows an increase
in the number of VNS operations between 1998 and 2003, followed
by a slight drop in 2004 and 2005 (Baaj et al., 2008). In contrast,
although NAEC data confirms this drop in VNS implantation in
2004, there have been dramatic increases subsequently. In 2010,
NAEC data suggests that VNS became the most common epilepsyrelated surgical procedure performed in the US, surpassing the
number of temporal and extratemporal lobe resections combined
in 2011 as well as 2012. The utilization of VNS over all resective
surgeries has been confirmed in the UK (Neligan et al., 2013) and
worldwide, more than 99.5% of VNS implants in 2011 and 2012
were for epilepsy (Personal Communication: Cyberonics, Finance
Department. Aug 2013—http://ir.cyberonics.com/results.cfm). The
apparent explosion in VNS usage, an expensive and mildly palliative
rather than curative option, and which does not replace medication,
is intriguing and requires scrutiny that is beyond the scope of this
data.
Conclusion
There appears to be a disconnect between projected numbers of
epilepsy surgery candidates in the US and current annual rates of
surgery despite an expansion in epilepsy centers and center infrastructure. This is likely to have significant implications in healthcare
resource planning. The precise factors that underpin this are currently speculative but certainly merit further study. Efforts focusing
on the mechanisms responsible for the development and evolution of drug resistant epilepsy, and on more effective treatments
than those currently available for patients who are not surgical
candidates and/or those who fail surgery are more important than
ever.
Acknowledgements
The authors would like to sincerely thank the National Association of Epilepsy Centers for sharing and allowing analysis of their
data. Drs. Kaiboriboon and Lhatoo received support from the Centers for Disease Control and Prevention (Grant no. 3U48DP001930).
109
Dr. Lhatoo received support from the National Institute of Neurological Disorders and Stroke (Grant no. P20NS076965).
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