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Remedy Publications LLC., | http://clinicsinsurgery.com/
Clinics in Surgery
2019 | Volume 4 | Article 2546
1
Presurgical Assessment and Surgical Treatment in Extra
Temporal Lobe Epilepsy: A National Comprehensive
Epilepsy Surgery Program in Cuba
OPEN ACCESS
*Correspondence:
Lilia Maria Morales Chacón,
International Center for Neurological
Restoration, National Epilepsy Surgery
Program, 25th Ave, No 15805, Havana,
Cuba, Tel: +53-72-730-920;
E-mail: lily@neuro.ciren.cu
Received Date: 19 Jun 2019
Accepted Date: 02 Aug 2019
Published Date: 12 Aug 2019
Citation:
Morales Chacón LM, González JG,
Cordero NQ, Ríos M, Romanidy MD,
Bender del Busto JE, et al. Presurgical
Assessment and Surgical Treatment
in Extra Temporal Lobe Epilepsy: A
National Comprehensive Epilepsy
Surgery Program in Cuba. Clin Surg.
2019; 4: 2546.
Copyright © 2019 Lilia Maria Morales
Chacón. This is an open access
article distributed under the Creative
Commons Attribution License, which
permits unrestricted use, distribution,
and reproduction in any medium,
provided the original work is properly
cited.
Research Article
Published: 12 Aug, 2019
Abstract
is paper presents an Electro clinical outcome of Extra Temporal Lobe Epilepsy (ExTLE) patients
derived from a national comprehensive epilepsy surgery program in Cuba. Twenty-three patients
with pharma co resistant Ext TLE underwent thorough pre surgical evaluations as well as resective
and disconnective surgical procedures tailored by sequential intra operative ElectroCorticography
(ECoG). Seizure outcome assessment for each patient was carried out one and two years aer seizure.
Logistic regression analysis was used to consider the potential predictive factors, which included
demographic, presurgical and surgical variables. Resective surgical techniques were performed on
frontal, occipital, pericentral and parietal lobes. Hemispherectomy was implemented in one patient
for Rasmussen encephalitis. Anterior callosotomies for drop attacks were completed in two children;
and focal frontal resection was carried out in one patient additionally to anterior callosotomy.
About 80.9% of the surgeries were done in non-dominant hemispheres. Furthermore, surgical
resection encroaching upon eloquent cortex was accomplished in 42.8% of the Ext TLE patients.
During presurgical evaluation, the most common seizure types were aware and non-aware focal
seizure which evolved to bilateral tonic clonic seizures. Regional interictal Electroencephalography
pattern was documented in 61.5% of the patients; while 66.6% exhibited non-lateralized or bilateral
interictal epileptiform discharge. Ictal EEG pattern was lateralized in 69.2% and regional in 76.9%
of the cohort. Magnetic Resonance Imaging did not indicate a distinct lesion in 52.1% of the
cases. Aer one-year follow up, 52.6% was labeled (Engel class I) and 47.3% (class II-III); at 24
months: 41.1% cases were registered class I, and 58.8% class II-IV. Clinical evolutions did not show
signicant modication concerning the assessed terms (Friedman ANOVA p=0.15); and there
was no variation in the number of cases registered Engel class I two years aer surgical treatment
compared to the previous year (p=0.47 Sign test). A drop in the Absolute Spike Frequency (ASF)
was observed in the post resective intra operative ECoG performed in all resective surgeries. e
ASF during pre-resection ECoG was lower in patients Engels Class I one and two years aer surgery
(*p<0.05, Mann U test). A multivariate logistic regression analysis demonstrated that an acute
postoperative seizure was the sole postoperative variable related to Engel classication. (p=0.01),
odd ratio 3.88. is multi-disciplinary and multi-modal program for presurgical epilepsy workup
and surgical procedures guided by sequential intra operative ECoG indicates favorable outcomes
that show a safe and viable procedure with mild morbidity, and no mortality.
Keywords: Extratemporal lobe epilepsy; Epilepsy surgery; Seizure outcome; Intraoperative
Electrocoticography
Lilia Maria Morales Chacón*, Judith González González, Nelson Quintanal Cordero, Martha
Ríos, Manuel Dearriba Romanidy, Juan E. Bender del Busto, Aisel Santos Santos, Margarita M.
Báez Martin, Sheila Berrillo Batista, Randis Garbey Fernández, Zenaida Hernández Díaz, Karla
Batista García-Ramo, Bárbara Estupiñan Díaz, Lidice Galán García, Marilyn Zaldívar Bermúdez,
Maite Solomon, Orestes López Piloto, Lourdes Lorigados Pedre, Liana Portela, Ricardo Valdés
Yerena and Abel Sánchez Coroneux
International Center for Neurological Restoration, National Epilepsy Surgery Program, Cuba
Introduction
About one-third of epilepsy cases exhibit pharmaco-resistant seizures; and approximately
70% among those are identied with Temporal Lobe Epilepsy (TLE) while the residual 30% are
characterized by extratemporal lobe epilepsy seizures [1,2]. Extratemporal Lobe Epilepsy (ExTLE)
involves a range of seizures which can arise from the cerebral cortex outside of the temporal lobe;
making up Frontal Lobe Epilepsy (FLE) the majority of those cases [3].
Nowadays, hitches in dening the epileptogenic zone, ascertaining the borders of the surgical
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
2
resection, and the connection of the epileptogenic zone to high
functionality areas still make surgical management of extra temporal
epilepsies demanding.
Current developments in noninvasive procedures such as epilepsy
specic Magnetic Resonance Imaging (MRI) protocols comprising
post processing analysis, Single Photon Emission Computed
Tomography (SPECT) and Positron Emission Tomography (PET)
have enhanced the ExtTLE diagnostic tools, enabling surgical behavior
[4-6]. Likewise, intra operative Electrocorticography (ECoG) might
also provide useful information in relation with the interictal activity
varying the planned resection extension [7].
Nonetheless, outcomes of surgical treatment in TLE are more
satisfactory than in ExTLE. In addition, existing technology is not
usually available in developing countries where 80% of epilepsy
patients do not have comprehensive epilepsy surgery programs,
especially, to treat pharmacoresistant ExTLE epilepsy [8]. at is
why; hard work is done to categorize foretelling features that help
describe potential candidates for resective surgery [9-12]. Considering
the needs previously stated, we set up the rst comprehensive
epilepsy surgery center in Cuba [13]. is paper summarizes
presurgical assessment and surgical treatment in extratemporal
lobe epilepsy patients, and communicates the establishment of a
national comprehensive Epilepsy Surgery Program in Cuba. e
study examines a cohort of patients who underwent surgery for
pharmacoresistance extratemporal treatment, and identies pre and
surgical predictors of postoperative seizure recurrence.
Materials and Methods
Patient population
Subjects submitted to ExTLE epilepsy surgery with over one-
year follow-up aer operation was included in this communication
whereas those with prior brain surgical procedure were le out.
Additionally, cases were required to be non-responsive to at least
two Antiepileptic Drugs (AEDs) trials as a result of inecacy and
intolerance; thus, recurrently compromised by seizures. Individuals
with pharmacoresistant epilepsy were referred from all the country
[14]. Family and patient´s approval was received in all cases.
Presurgical examination
e presurgical examination plan included: (a) prolonged Video-
Electroencephalography (V EEG) monitoring with scalp electrodes
placed according to the international 10 to 20 system and additional
electrodes considering the epileptogenic zone presumed; (b)
Magnetic Resonance Imaging (MRI) scans with a 1.5T or 3T scanner
(Siemens Magnetom Symphony) (c) A comprehensive battery of
neuropsychological tests (executive functions, attention assessment
and memory, higher verbal and visual functions), (d) multimodal
evoked potentials, somatosensory, visual and auditive [15-17]. In
patients with non-visible lesion in MRI interictal and ictal brain
perfusion Single Photon Emission Computed Tomography (SPECT)
using 99mTc-Ethylene-Cysteine Dimer (ECD) were carried out.
During the administration of the radiopharmaceutical, the patient
remained monitored by EEG. e SISCOM methodology was also
implemented in this cases Figure 1A. Besides, MRI post processing
comprising voxel based morphometric and volumetric analysis with
functional neuroimaging using Magnetic Resonance Spectroscopy
(MRS) were also implemented in these patients in accordance with
our previously published protocol [16].
Presurgical video-EEG monitoring: Patients underwent
Video-EEG monitoring for 6.6 ± 2.74-day range (1 to 11 days). e
distribution of Interictal Epileptiform Discharges (IEDs) during
prolonged video-EEG monitoring was assessed by (LM) analyzing
een- minute-interictal EEG samples every one hour. e data
recorded in relation to events was identied by button presses, seizure
or spike detection programs.
Interictal epileptic form activity and ictal onset pattern were
categorized as regional involving one lobe, and ipsilateral contiguous
or non-regional [1,2]. Ictal and interictal Video-EEG were analyzed
by a well-qualied epileptologist (LM).
Presurgical magnetic resonance imaging: Presurgical 1.5 (n=9)
or 3T (n=14) MRI scans of the patients integrating T1-weighted
images with and without gadolinium-DTPA, T2-weighted images,
uid-attenuated inversion recovery images and magnetization-
prepared rapid gradient echo sequences were also reviewed by a
knowledgeable neuroradiologist (ZH). MRI ndings were classied
as (1) MR visible/MR non-visible; (2) according etiology, tumor,
cortical development malformation, vascular and others; and (3)
(eloquent cortex/non-eloquent) adjacent to or overlapping with
eloquent areas (the primary motor cortex or Broca’s area, sensorial,
language) based on anatomic landmarks; (4) laterality (dominant
hemisphere/non-dominant). Since 2016, we have discussed patient
test results monthly, not only with a multidisciplinary team at epilepsy
surgery conferences held at our Center, but also with specialists of the
national epilepsy surgery program.
Surgical procedures and histopathology
Surgical procedures encompassed local resection, functional
hemispherectomy, multiple subpial transection, and corpus
callosotomy. Lobectomy was the prime practice when all or most
parts of the lobe were involved in the epileptogenic zone. In addition,
lengthy lesionectomy was performed in patients with local seizure
onset and MRI visible lesion. e extension of the resection was
tailored by sequential pre and post resection ECoG. Eloquent cortical
areas were labeled according to Changes taxonomy; and comprised
the rolandic cortex (pre- and postcentral gyrus), the Supplementary
Motor Area (SMA), insula, primary visual cortex as well as Broca and
Wernicke´s areas [18].
ECoG data acquisition was performed with a Medicid-5 digital
Electroencephalographic system (Neuronic SA, Cuba) using AD-
TECH subdural electrodes (grid and strips). In the pre and post
resection ECoG Absolute Spike Frequency (ASF) were calculated, and
variation percentage of the ASF was also estimated. e extension of
resection in lesional and non lesional cases was adjusted according to
presurgical evaluation and intra operative sequential ECoG. Subtotal
resection was intentionally performed when the lesion overlapped
with eloquent cortex. e accurate detection of lesion localization
relative to eloquent cortex was derived from intraoperative ECoG
using cortical mapping with somatosensory evoked potentials and
electrical stimulation Figure 1B.
Histopathological analysis: In this study, epilepsy substrates
were determined by histopathology, and resected specimens varied
in size depending on the presurgical evaluation and intra operative
ECoG results. Haematoxylin-eosin and Kluver-Barrera myelin special
stain were performed in specimens. Histopathological ndings
comprised four chief groups: cortical development malformations,
neoplasms, vascular lesions, and other nonspecic histopathological
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
3
abnormalities. For microscopic diagnosis and Focal Cortical
Dysplasia classication, the system proposed by the International
League Against epilepsy was used [19]. For Central Nervous System
tumor histopathological diagnosis purpose, the World Health
Organization (WHO) classication was employed [20]. Unspecic
histopathological abnormalities included gliosis, scars, among others.
Neoplasms were classied as glial tumors (astrocytomas,
oligoastrocytomas, and oligodendrogliomas) and neuroepithelial
tumors (gangliogliomas and Dysembryoplastic Neuroepithelial
Tumors [DNTs]).
Seizure outcomes
Patients were routinely evaluated twelve, and twenty-four
months aer surgery. Some cases were gauged at appropriate
intervals of seizure recurrence. Seizure outcome assessment was
based on Engel´s scale [Engel class I, free of disabling seizures; class
IA, seizure-free; class II, rare seizures (fewer than three seizures per
year); class III, worthwhile improvement (reduction in seizures of
80% or more); class IV, no benet] [21]. To exemplify, class I was
categorized as “satisfactory” outcome, while classes II, III and IV as
“non-satisfactory” seizure relief outcome.
In patients with acute postsurgical seizures, the recurrence period
was determined by the time of the rst seizure aer one postsurgical
week. For the interests of this study, acute postsurgical seizures were
dened as those occurring within the rst postoperative week (<7
days).
Statistics study
Data were collected from follow-up visits, and sequentially
entered into the database. Indicators were summarized with
descriptive statistics for each variable comprising means, medians,
and standard deviations for continuous variables and frequencies for
categorical variables. Normality of the data was tested using Shapiro-
Wilk test. Results showed non-normal distribution of some variables
for comparisons, non-parametric inference was used. Mann Whitney
test was employed to compare dierences between two independent
populations. Additionally, the Friedman ANOVA and sign test were
utilized to assess the electroclinical follow-up one and two years
following surgery. A signicance level of 0.05 was used. Multivariable
analyses were performed by logistic regression to examine the
potential predictive and prognostic factors, including demographic,
presurgical and surgical analyzed variables.
Mean age at surgery (years ± SD range) 24,1±10,1 (range5-47)
Mean age at seizure onset (years ± SD range) 7.5 ± 5,18 (range 1-20)
Gender Male: 18/23 (55%)
Female: 5/23 (45%)
Mean epilepsy duration (year ± SD range) 17.1 ±10.5 (range 2-42)
< 5 years 3/23 (13 %)
> 5 years 20/23 (86.9 %)
Risk factors, n (%) 77.5%, (47.6% perinatal insult)
Mean number of antiepileptic drugs t± SD (range) 2,9 ± 0.6, (range 2–4)
Seizure frequency n (%) < 20/ months 21%
> 20/months 84.2%
Generalized tonic clonic seizure occurrence, n (%) Yes 56.5%
No 43.4%
Seizure types Aware and non-aware focal seizure evolved to bilateral tonic clonic seizure 5/23 (21.7%)
Non aware focal seizure evolved to bilateral tonic clonic seizure 6/23 (26%) Aware and non-aware focal seizure
7/23 - 30.4%
Non aware focal seizure 2/23 (8 %) motor and non motor generalized seizure in 2/23 (8 %)
Non aware focal seizure and motor and non-motor generalized seizure 1/23
Interictal EEG topography, n (%) Regional (61.5. %)
Non-regional (38.4 %)
Interictal EEG lateralization EEG, n (%) Lateralized (33.3 %)
Non-lateralized (66.6 %)
Ictal EEG topography, n (%) Regional (76.9 %)
Non-regional (23%)
Ictal EEG lateralization, n (%) Lateralized (69.2 %)
Non lateralized (30.7 %)
MRI lesion, n (%) MRI visible (47.8%)
MRI non-visible (52.1%)
SPECT interictal e ictal with EEG co registration,
n (%) Yes (42.1%)
No (57.8%)
Table 1: Demographic and presurgical assessment of the overall cohort of extratemporal epilepsy patients.
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
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Ethical considerations
e current study was accepted by the scientic and ethics
committee of the International Center for Neurological Restoration
(CIREN37/2012), and all the actions accomplished followed the
guidelines of the Declaration of Helsinki for human research from
1975.
Results
e Comprehensive Epilepsy Surgery Program aimed at carrying
out epilepsy surgeries at signicantly concessional rates began at
CIREN Havana, Cuba in 2001. In 2010, sporadic extratemporal
lesional epilepsy surgeries were practiced. Four years later, a regular
surgery program to extratemporal epilepsy was established. In May
2016, we set up a comprehensive national epilepsy surgery program
in pediatric and adult epilepsy patients incorporating the National
Neurosurgery and Neurological Institute as well as the pediatric
hospital “Juan Manuel Marquez", in order to optimize human and
technological resources, extent the comprehensive epilepsy surgery
program to other centers, and to perform epilepsy surgery in non
lesional and/or epileptogenic zone adjacent to or overlapping
eloquent cortex cases.
Demographic prole and presurgical assessment
Most patients (86.9 %) had more than ve years of seizure
duration. Mean age at seizure onset was 7.2 ± 5.2 (range 1 year to
20 year.), and presurgical seizure frequency was 20/months or more
in 84.2%. All patients had been taking 2 to 4 antiepileptic drugs
being Lamotrigine 47.3%, Carbamazepine 36.8%, Clonazepan 31.5%,
Valproic Acid 21%, Clobazan 31.5%, Levetiracetan 26.3% the most
frequent Antiepileptic Drugs (AEDs). About 47% were taking three
or more AED at surgery time Table 1.
Pre-surgical assessment: During extracranial Video-EEG
monitoring a mean of 24.6 ± 23.6 seizures per patient was recorded
with a mean Video-EEG monitoring eciency equal 0.72. In the
whole group the rst seizure occurred from day 1; and the third on
day 4. Data about awake and sleep seizures per day were 1.88 and
0.37 respectively. Regional interictal EEG pattern was documented
in 61.5% of the cases while 66.6% had non-lateralized or bilateral
Interictal Epileptiform Discharges (IED) (Table 1). In contrast, ictal
EEG pattern was lateralized in 69.2% and regional in 76.9% of the
10 subjects. Most patients exhibited aware and non-aware focal
seizures which evolved to bilateral tonic clonic seizures. MRI did not
illustrate a distinct lesion in 52.1% of the cases. On the other hand,
patients submitted to 3T MRI did not indicate more positive ndings
compared to patients who underwent 1.5T MRI. Besides, lesional
cases on MRI showed a lesion limited to the frontal lobe (44.4%) and
extra frontal lesion (55.5%).
Surgical procedures
Table 2 shows an overview on surgical variables. Resective
processes were located as follows: frontal (n=12), occipital (n=4),
pericentral (n=3) and parietal (n=1). About 77.7% of the surgeries
were performed in non-dominant hemispheres whereas 47% of the
ExTLE patients underwent surgical resection encroaching upon
eloquent cortex. e resection amount in patients was based on a
result combination obtained from presurgical evaluation and intra
operative ECoG ndings. Multiple subpial transections were done
additionally to resection in eloquent areas in ve patients (two in
primary motor and three in pericentral cortex). Hemispherectomy
was implemented in a patient due to Rasmussen encephalitis. Anterior
Figure 1: A. Presurgical evaluation in non lesional extra temporal epilepsy. Magnetic resonance imaging T1- and T2-weighted sequences were normal. Extracranial
EEG shows rhythmic activity at seizure onset in channels containing the frontocentral leads. SISCOM study performed in the patient allowed the detection of focal
hyper perfusion in the right sensory motor area during ictal SPECT. B. Intraoperative Electrocorticography reveals repetitive spike pattern. This activity was
recorded in the pericentral region. Somatosensory evoked potential was recorded to delineate eloquent cortex and it showed phase reversal in the contact over
rolandic area. This patient was submitted to a focal resection and histopathological examination reported focal cortical dysplasia type I according ILAE classication.
Figure 2: Bar graph shows values of absolute spike frequency on the pre
and postresection intraoperative Electrocorticography (mean and standard
deviation SD) in extratemporal lobe patients with satisfactory (Engel class
I) and unsatisfactory (Engel class II–IV) outcome. The absolute spike
frequency during pre-resection Electrocorticography was lower in patients in
Engels Class I (*p<0.05, Mann Whitney U test).
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
5
callosotomies for drop attacks were performed in two children; in
one case both focal frontal resection and anterior callosotomy were
carried out.
Intraoperative electrocorticography: ndings and surgical
outcome: Pre resection and sequential post resection ECoG was
performed in all patients. e numbers of sequential ECoGs were
between 2 to 4 records and the mean duration of the records was
16.78 ± 8.25 min. Bispectral index monitoring in between 38 to 70
was used to monitor depth of anesthesia. Repetitive interictal spikes
and other specic patterns of interictal spikes were seen in 83.3% of
the cases, and absolute spike frequency decreased signicantly in the
last post-resection ECoG, p=0.001 (Wilcoxon Matched pairs test).
e ASF during pre ECoG was lower in patients in Engels Class
I one and two years aer surgery (*p<0.05, Mann U test) as shown in
Figure 2A specic pattern of interictal spikes was recorded in 83.3%
of the cases, being also lower in patients with satisfactory postsurgical
outcome.
Histopathological ndings: As shown in Table 2, malformations
of cortical development accounted for 61.1% of all histopathological
ndings followed by neoplasms and cavernomas. About 16.6%
revealed nonspecic histopathological ndings, and one case had
microangiomatosis. Cortical development malformations were the
most common histopathological ndings in our series. ere was
similar proportion of patients with FCD type I, and Type II (40%
vs. 60%) [p=0.30 dierence between two proportions], one patient
had polymicrogyria, while other presented heterotopy associated
with FCD. In addition, neoplasms observed were glial tumors
(astrocytomas, and neuroepithelial tumors (gangliogliomas and
Dysembryoplastic Neuroepithelial Tumors [DNTs]).
Seizure outcome
Aer one-year follow up, 52.6% was categorized (Engel class
I) and 47.3% (class II-III); at 24 months, 41.1% of the cases was
registered class I, and 58.8% was listed class II-IV. ere was no
dierence between clinical evolutions considering the evaluated
periods (Friedman ANOVA, p=0.15). e percentage of patients
regarded as Engel class I did not diminish a couple of years aer
operation in relation to the preceding year (p=0.47 Sign test) Figure
3. APOS was seen in 56.2% of the cases, and patients kept their AEDs
for at least 2 years post-surgery.
Surgery Type
Frontal resection 12
. Primary motor area 2
. Supplementary Motor Area (SMA) 2
. Dorsolateral 6
. Orbitofrontal 2
Pericentral resection 3
Parietal resection 1
Occipital resection 4
Corpus Callosotomies 2
Functional Hemispherectomy 1
(Multiple subpial transection was done additionally to a resection in 5 cases
associate with a focal resection)
1 callosotomy was done in addition to a frontal resection)
Laterality, n (%) dominant hemisphere 19%
Non-dominant 80.9%
adjacent to or overlapping with eloquent areas eloquent cortex 42.8%
non-eloquent) 57.1%
ECoG pattern Specic patterns of interictal spikes Yes 83.3%
No 20%
Presection ECoG Interictal epileptiform discharges Absolute Discharges
Frequency (ADF) 51.45± 112.5/min (range 1.89 -464.15)
Postresection ECOG Interictal epileptiform discharges Absolute Discharges
Frequency (ADF) 7.64 ± 8,56/min (range 1.05-32.9)
ECoG variation percentage of the Interictal epileptiform discharges Absolute
Discharges Frequency (ADF) 80.06 ± 13.5 % (range62.9-100)
Histopathology, n (%)
Cortical development malformations (61.1 %)
Tumor (16.6 %)
Cavernoma (5 %)
Microangiomatosis 5%
Not specic (16.6 %)
Rassmussen encephalitis associated to FCD 1 patient
APOS, n (%) Yes 56.25 %
No 43.75%
Table 2: Surgical histopathological and electrocorticographic characteristics of the overall cohort of extratemporal epilepsy patients.
ECoG: Electrocorticography; APOS: Acute postoperative seizures; SD: Standard deviation
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
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Logistic regression analysis demonstrated that the APOS was
the only postoperative factor associated with Engel classication
outcome. (p=0.01), odd ratio 3.88. Moreover, occurrence of bilateral
tonic clonic seizures and lesional MRI showed a tendency to predict
seizure outcome in this cohort.
Operative complications: As to surgical complications, there
was no mortality in our cohort. However, postoperative neurological
decits like paresis were perceived in three patients whereas
other three cases showed surgical complications such as deep vein
thrombosis, wound infection, and visual dysfunction, respectively.
Most of these conditions were resolved during the postoperative
course. Permanent neurological morbidity was observed in only three
patients (13%), described as paresis and sightlessness. On the other
hand, one patient Engel Class I, died from cardiovascular disease
een months aer surgery.
Discussion
Results demonstrate that surgery in patients with extra-
temporal epilepsy is related to promising seizure outcome and
minimum complication outline. e success of this comprehensive
national epilepsy surgery program in pediatric and adult epilepsy
patients strongly suggests the possibility of developing a committed
comprehensive epilepsy surgery program with a national collaborative
approach in a Latin American region. One year aer surgery, 52.6 %
of the patients was cataloged Engel I class. is result is in line with
Tellez-Zenteno et al report; and to some extent improved in relation
to other series [9,11,22,23]. e surgical outcome in our cohort is
also consistent with a large case surgery series for extratemporal lobe
epilepsies reported, in which 49% of the patients were Engel Ia at an
average of 54 months postoperatively [2]. In Delev D's report, Engel
I outcome aer frontal and parietal resections was 65% and 71%,
respectively, while other studies informed Engel I outcome ranging
from 45.1% to 57.5% [24-26].
A variety of information for seizure outcome aer extratemporal
resections is particularly noticeable in the available works. Some
authors have reported moderately steady Engel I rate over years in
nearly 50% adults and children [9,27,28]. Controversially, McIntosh
et al. [29] stated initial seizure freedom in 40.7% of the cases, falling
to 14.7% ve years aer operation [29]. Furthermore, a retrospective
study that involved children with FCD and benign tumors submitted
to frontal lobe resection described that at last follow-up, 63% patients
stayed seizure-free; however, 37% had discontinuance in antiepileptic
drugs [30]. Other series from Latin America and other developing
countries involved in temporal and extratemporal epilepsy surgery
such as Argentina comprising lobectomies, lesionectomies,
callosotomies, multiple subpial transection, vagus nerve stimulations
and hemispherectomies revealed Engel class I outcome in 68.21% at
12 months’ follow-up [31]. Mikati MA also stated 70% Engel class I,
9% class II, 14% class III, and 7% class IV aer resective surgery in 93
adults and children who had undergone epilepsy surgery including
extratemporal (22%), and temporal resections in 54% and multilobar
resections (13%), hemispherectomy (4%), vagal nerve stimulation
(6%), and corpus callosotomy (1%) of the cases at the American
University of Beirut [32]. On the other hand, Jayalakshmi S, reported
Engel's favorable outcome in temporal and extra-temporal resection
in adolescents and children respectively, in 59 (75.6%) of the cases
[33]. In addition, Vermeulen L informed good seizure outcome
for at least one year at the last visit in 62% for extra-temporal lobe
interventions [34]. Recently, satisfactory outcomes were observed in
92.5% of the pediatric patients submitted to corpus callosotomies and
resective procedures [35].
Most procedures carried out for extratemporal epilepsies are
frontal resections, which were performed in 52.1% of our cohort;
followed by occipital, pericentral and parietal resection as well as
palliative and disconnection procedures [36]. Equivalent ndings
were reported in Delev D's series, with 48% of frontal lobe operations,
whereas parietal, occipital, and insular resections accounted for
24% of the procedures [2]. ey also reported that the most positive
epileptological outcomes were attained in individuals with frontal
and parietal resections (Engel I 65.0% and 71.4%, respectively), as
insular resections revealed less auspicious results (Engel I 52.2%).
We executed corticectomy of Supplementary Motor Area (SMA)
guided by sequential ECoG in two patients classied as Engel Scale II
one year aer surgery. Recently, Alonso-Vanegas MA described that
61% of the patients who underwent lesionectomy and/or corticectomy
of the SMA guided by ECoG were Engel Class I. Concerning
functional hemispherectomy; reports have specied 66% in a group
of patients with grade I control according to Engel's classication, in
average follow ups of 48 months [8]. Observably, such comparisons
are restricted by both referral patterns and selection criteria, which
are expected to vary from dierent centers in Latin American nations.
So as to homogenize these criteria, cases were analyzed in an epilepsy
surgery conference including a multidisciplinary team with specialists
of the national epilepsy surgery program.
It can be noticed that a pathology-based approach to epilepsy
surgery is essential as it might improve not only the explanation
of the outcomes but also the understanding of the failure causes.
Noticeably, cortical development malformations, specically FCD
were the most common histopathological nding in our series, with
similar proportion between FCD Type I and Type II. Moreover, FCD
has been considered as a foremost reason of pharmacoresistant extra
temporal resections, especially in children and adolescents [37-39],
while the rate of seizure free once resection improved from 52% to
68.9% [40-42].
As described in other studies, we found a quite high prevalence
of FCD among operated cases with normal MRI [43-45]. In this
framework, some authors have pointed out that even the unseen
primary pathology, specically FCD, can represent a favorable
prognostic indicator in case of complete removal of the EZ when
compared with all other etiologies [46-48].
Figure 3: Bar graph shows comparison of clinical follow up using Engel
Scale in extratemporal lobe epilepsy patients submitted to epilepsy surgery
one and two years after surgery. No difference was seen between clinical
evolutions considering the evaluated periods (Friedman ANOVA p=0.15).
The percentage of patients in Engel class I, did not decreased two years post
surgery in relation to the previous year (p=0.47 Sign test).
Lilia Maria Morales Chacón, et al., Clinics in Surgery - Neurosurgery
Remedy Publications LLC., | http://clinicsinsurgery.com/ 2019 | Volume 4 | Article 2546
7
In one recent extra temporal series, FCD accounted for 46.5%
of all histopathological ndings followed by tumors, gliosis, and
cavernomas [2]. Similarly, in our study, astrocytomes, gangliogliomas
and DNTs were the tumors found in patients; being the latter of
the group of long-term epilepsy associated tumors. With respect
to histopathology, most favorable seizure outcomes have been
described in patients with cavernomas and glioneuronal tumors
(gangliogliomas and DNTs) with 89% and 85% seizure-free (Engel I)
patients, respectively. Consistent with previous reports, 2/3 (66.6 %)
our patients with tumor conditions remain seizure-free.
Even with this histopathological prole, our seizure freedom
outcome (Engel class I) was equivalent to other series in developed and
developing countries. is points to epilepsy surgery as an eective
treatment for carefully selected patients with pharmacoresistant extra
temporal lobe epilepsy.
Apart from the ambiguity concerning the choice of the most
prospective candidates, surgical treatment of extratemporal epilepsies
stays with diculties in localizing and dening the extension of
the epileptogenic zone. us, we also implemented a sequential
pre and postresection ECoG in order to dene the extension of the
epileptogenic zone in addition to developing a presurgical evaluation
based on multimodal data acquisition derived from ictal and
interictal SPECT coregistered with EEG, SISCOM and quantitative
neuroimaging in case with non-visible lesion in MRI [16;49].
e present work highpoints our practice with ECoG and its
usefulness in epilepsy surgery [50]. A signicant modication was
observed between pre and post resection Absolute Spike Frequency
(ASF) which was lower in patients classied Engels class I. It is
recognized that the attainment of epilepsy surgery is governed by
precise localization and entire resection of the epileptogenic tissue,
which are both assisted by intra operative ECoG. e presence of
persistent spikes on post-resection ECoG has been a noteworthy
numerical relation to poor seizure freedom post-surgery [51].
is author concluded that the intra operative ECoG is a valuable
adjunctive test in epilepsy surgery to accomplish ideal seizure freedom
in cases of mesial temporal sclerosis plus, focal cortical dysplasia and
tumors.
In contrast, there is extensive dierence in clinical practice about
the role of electrocorticography closely aer resection (post-resection
ECoG) in pediatric epilepsy surgery. It has been stated that results
can guide further resection of potentially epileptogenic tissue. On the
other hand, there is a hypothesis that post-resection ECoG spiking
represents a biomarker of the epileptogenic zone, and predicts seizure
outcome in children undergoing epilepsy surgery. In Geiner HM's
report, the best outcomes were obtained with resection of both the
seizure-onset zone and ECoG abnormalities [7].
As a whole, in terms of complications the rate is higher in extra
temporal location compared to temporal resections with a reported
perioperative mortality of 1.2% in extra temporal resections [52].
Appreciably, stable morbidity of extra temporal procedures uctuates
between 3% and 43% in dierent series [53-55]. In our study, there was
no mortality. Besides, long-lasting complications were only observed
in three of the cases, and surgical resections involved eloquent areas
in 42.8% (almost a half of the cases); hence, the complication number
appears to be reasonable.
Equally to Delev D's series, we had no perioperative death; and
permanent morbidity associated with surgical and neurological
complications reached 13% [2]. is gure is parallel to others
reporting a stable morbidity between 10% and 15% [2,27,28,56].
orough lesion resection, short term epilepsy, younger age at
surgical procedure, and circumscribed histopathological results
are among the most predictive variables related to seizure outcome
post ExTLE operation [27,57,58]. Moreover, remoteness from the
epileptogenic zone to eloquent cortex was linked to a more auspicious
outcome (Engel I), despite no meaningful eect on seizure outcome
of the resection localization [12].
It was observed that acute postoperative seizures were an
independent predictor of clinical outcome in our extra temporal
patients, being FDC the most common pathological substrate. is
result overlaps with Jin B et al. [59], who reported that incomplete
resection of FCD, presence of IEDs on 3 months to 6 months
postoperative EEG, and presence of habitual APOS are powerful
predictive factors for seizure recurrence aer surgery [59]. On the
other hand, in a large cohort of the spectrum of malformations of
cortical development including FCD, 66.67% of the patients were
seizure-free and aura-free at last follow-up. e authors detected
that shorter duration of epilepsy was the single most important pre-
operative variable, and that the absence of spikes in post-operative
EEG predicts a long-term favorable seizure outcome [60].
In this study, other clinical features available prior to resection
show a tendency to predict seizure outcome such as the occurrence
of generalized tonic clonic seizures and non lesional/lesional IRM.
is might help classify individuals who are likely to take advantage
of extra temporal surgical procedure.
In a recent revision, a multivariate study described that observable
lesions on MRI, non-eloquent location, absence of postoperative
seizures, circumscribed pathology, patient age under 18 at surgery
(<18 yr), and epilepsy duration correlated with better seizure outcome
in extra temporal epilepsy [2].
Conclusion
A multi-disciplinary and multi-modal program for presurgical
epilepsy workup and surgical procedures for extra temporal
pharmacoresistant epilepsy guided by sequential intra operative
ECoG indicates favorable outcomes. e approaches adopted show
a safe and viable procedure with mild morbidity and no mortality.
Limitations
e low sample size precludes the extraction of valuable
information about potential prognostic factors in this study; however,
the standardized diagnostic and surgical procedures in extratemporal
pharmacoresistant epilepsy still provide relevant information. e
outcomes reveal a number of patients being seizure-free similar to
other series, and emphasize the value of presurgical assessment and
sequential ECoG in extra temporal epilepsy surgery outcome.
Authors Contribution
e authors of this article were all extensively involved in the
surgical program. Dr. Morales was responsible for designing the
project. In addition to analyzing and discussing the results she also
wrote the paper.
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