RESEARCHHUMANCLINICAL STUDIES
TOPIC
DOI: 10.1227/NEU.0b013e31823f6001
www.neurosurgery-online.com
approach. Antiepileptic drugs reduce the recurrence of seizures13-15 but demonstrate considerable, and often restricting, side effects,16 and
their role in affecting long-term remission is
questionable.14,17 Moreover, a significant proportion of patients who are seizure free on
medications relapse after discontinuation of
antiepileptic drug treatment,18-20 and a subset
of patients continue to experience debilitating
seizures despite maximal medical treatment.21-24
For such patients with medically intractable
epilepsy, surgery is often considered for successful multimodal treatment directed at controlling
seizures and averting developmental delay.
Surgical complications of epilepsy surgery have
been declining with increased experience and
www.neurosurgery-online.com
improved diagnostic and surgical techniques.25-27 Surgical resection in the region of the supplementary motor area (SMA),
critical for planning and execution of voluntary motor function,
has been shown in adults to result in a distinctive transient
neurological condition known as SMA syndrome.28-39 First
described after surgical resection by Laplane et al,33 the syndrome
has a strikingly consistent clinical evolution postoperatively,
characterized by transient hemiparesis or motor apraxia with
variable degrees of speech arrest followed by rapid recovery of
neurological impairment.
We examined the development of SMA syndrome in a series of
39 children who underwent surgery for resection of a seizure focus
in the medial frontal cortex. In addition, we analyzed seizure
outcomes after surgery. To the best of our knowledge, this report
represents the largest study of SMA syndrome after surgery in the
medial frontal lobe and is the first to be done in an exclusively
pediatric patient population.
METHODS
Patient Population and Preoperative Evaluation
After Institutional Review Board approval was granted at the St. Louis
Childrens Hospital/Washington University in St. Louis Human
Research Program and Cincinnati Childrens Hospital Medical Center,
medical records of patients who underwent surgical management for
medically intractable epilepsy between 1994 and 2010 were reviewed.
Patients with resections in the medial frontal lobe were included in the
study. Table 1 summarizes the patient and seizure characteristics of
39 patients who met these inclusion criteria. Preoperative evaluation was
tailored for each patient and included magnetic resonance imaging
Operative Approach
TABLE 1. Demographics and Seizure Characteristics in Patients
Who Underwent Surgical Treatment in Medial Frontal Lobe for
Medically Intractable Seizuresa
Total patients, n
Female sex, n (%)
Right handedness, n (%)b
Age at seizure onset, mo
Age at surgery, mo
Time between seizure onset and surgery, moc
Seizure type, n (%)
CPS
CPS-secondary generalized
SPS
SPS-secondary generalized
Multiple seizures/generalized
Seizure types (25th, 75th percentiles), n
Preoperative seizure frequency, n (%)c
Monthly
Weekly
Daily
a
NEUROSURGERY
39
19 (49)
24 (71)
62.1 6 50
146 6 57
82.5 6 60
14
4
7
4
10
2
(36)
(10)
(18)
(10)
(26)
(1, 2)
4 (11)
6 (16)
28 (74)
Thirty-five patients (89.7%) had subdural electrocorticographic monitoring with electrode grid and strip arrays, depth electrodes, or
a combination thereof. The operative approach for each patient was
determined after neuroimaging studies, video-EEG, intraoperative and
extraoperative mapping, and evaluation by the St. Louis Childrens
Hospital and Cincinnati Childrens Hospital Medical Center multidisciplinary epilepsy teams. The location and extent of surgical resection
were determined through postoperative MRI and tabulated (Table 2).
This information was available for 34 patients (87.2%). Specimens from
patients were sent for pathological evaluation.
Statistical Methods
Data are presented as mean 6 SD for continuous variables and median
(25th and 75th percentiles) for ordinal variables. For categorical
variables, data are the number of patients (percent of group). Unless
otherwise noted, the Wilcoxon test was used for comparisons of
continuous variables, and the Fisher exact test was used for comparison
of categorical variables. For correlation studies, the Spearman correlation
was used to analyze data. A value of P # .05 was considered statistically
significant. A denominator is included when less than the complete
patient cohort provided data for the categorical variables. The data
analysis was generated with SAS software version 9.2 of the SAS System
for Linux (SAS Institute Inc, Cary, North Carolina).
KASASBEH ET AL
TABLE 2. Extent and Location of Surgical Resection and Association Between Neurological Deficit and Resection Parametersa
Neurological Deficit (25th, 75th Percentiles), cm
Variable
Distance anterior to precentral sulcus, cm
Distance superior to cingulate gyrus, cm
Distance lateral to fissure, cm
Anteroposterior extent of resection, cm
Superior-inferior extent of resection, cm
Transverse extent of resection, cm
0.50
0.60
0.05
3.95
2.90
3.00
Entire
Group
No Impairment
(n = 12)
SMA Syndrome
(n = 16)
(0, 1.62)
(0, 1.00)
(0, 3.29)
(3.07, 5.70)
(2.10, 4.80)
(1.90, 3.70)
2.22
1.00
0.40
3.51
4.12
3.03
0.20
0.52
0.50
4.13
3.15
2.98
(1.00,
(0.30,
(0.00,
(2.25,
(2.30,
(2.15,
3.26)
1.24)
2.52)
4.05)
5.92)
4.35)
(0.00,
(0.00,
(0.00,
(3.34,
(2.04,
(1.80,
1.45)b
0.85)
3.47)
5.73)
4.55)
3.70)
Permanent Impairment
(n = 6)
0.00
0.00
0.05
5.28
2.55
2.90
(0.00,
(0.00,
(0.00,
(3.10,
(2.25,
(1.90,
0.00)b
0.75)b
0.30)
6.75)
3.00)
3.00)
P
.001
.05
.67
.08
.35
.57
a
SMA, supplementary motor area. P value compared groups by analysis of variance with rank-transformed data. When significant, pairwise between-group comparisons were
performed with Tukey-adjusted least-squares means. Significant pairwise comparisons are noted.
b
P , .05 vs no impairment by Tukey-adjusted least-squares means.
RESULTS
Patient and Seizure Characteristics
Thirty-nine patients underwent surgery in the region of the
medial frontal lobe for medically intractable epilepsy at St. Louis
Childrens Hospital and Cincinnati Childrens Hospital Medical
Center from 1994 to 2010 (Table 3). Of the 39 patients included
in the study, 19 (49%) were female and 20 (51%) were male.
Right-handedness was demonstrated in 24 of 34 patients (71%).
The age at onset of seizures was 62.1 6 50 months, and age at the
time of surgery was 146 6 57 months. Surgery was performed
82.5 6 60 months after identification of epilepsy. With regard to
seizure characteristics in the study cohort, 14 (36%) had complex
partial seizures, 4 (10%) had complex partial seizures with
secondary generalized tonic-clonic seizures, 7 (18%) had simple
partial seizures, and 4 (10%) had SPS with secondary generalization. Multiple seizure types were found in 10 patients (26%).
The median number of seizure types in the patient population
was 2. Seizures were experienced daily in 28 patients (74%),
weekly in 6 patients (16%), and monthly in 4 patients (11%). All
patients failed AED therapy with at least 2 drugs at therapeutic
doses. Patient demographics and seizure characteristics are
summarized in Table 1. Table 3 lists individual patient information, including demographics, clinical profile, pathology, and
neurological impairment after surgery.
Neurophysiologic Monitoring and Surgical Resection
Thirty-five patients (90%) underwent invasive subdural monitoring before surgical resection. Lesionectomy was performed in 8
patients (21%). Tailored resections were performed in the
remaining 31 patients (79%), with 5 patients (13%) undergoing
multiple subpial transections in addition to tailored resections. In
all cases, intraoperative cortical stimulation mapping and somatosensory evoked potentials were used to localize the eloquent
primary motor cortex and central sulcus. In cases when intraoperative cortical stimulation mapping and/or somatosensory
evoked potentials were unreliable (particularly in the younger
www.neurosurgery-online.com
NEUROSURGERY
TABLE 3. Demographics, Clinical Profiles, Pathology, and Outcome in Patients Who Underwent Resection of Medial Frontal Lobea
Patient
Age at Surgery,
mo
Sex Handedness
Seizure Type
Side of
Surgery
175
188
106
71
147
68
M
F
M
M
F
F
L
L
L
R
R
R
SPS-secondary generalized
CPS
CPS
Multiple seizures/generalized
SPS-secondary generalized
SPS
L
L
R
L
L
R
7
8
137
99
M
M
L
R
Multiple seizures/generalized
SPS-secondary generalized
L
L
114
N/A
10
11
12
13
200
182
10
196
F
M
F
F
R
R
R
L
14
15
16
109
233
185
F
M
F
R
N/A
R
17
127
18
19
203
195
F
F
L
L
20
148
21
22
23
24
25
26
180
59
169
209
7
183
M
M
F
M
F
F
R
L
R
R
N/A
N/A
27
180
28
97
N/A
Immediate Postoperative
Neurological Impairment
N/A
Nonspecific changes
Cortical dysplasia
Hypoxic-ischemic cell damage
Heterotopia
No significant histopathological
abnormality
AVM and capillary telangiectasia
No significant histopathological
abnormality
Nonspecific changes
No neurological impairment
No neurological impairment
No neurological impairment
No neurological impairment
No neurological impairment
Contralateral hemiparesis, contralateral facial
weakness
No neurological impairment
Contralateral hemiparesis (did not resolve by
12-mo follow-up visit)
Contralateral hemiparesis, contralateral facial
weakness (hemiplegia did not resolve by
12-mo follow-up visit)
CPS
CPS
Multiple seizures/generalized
Multiple seizures/generalized
R
R
R
L
Nonspecific changes
Nonspecific changes
Subpial and subcortical gliosis
Nonspecific changes
Contralateral hemiplegia
Contralateral hemiparesis
No neurological impairment
Contralateral hemiparesis, mild contralateral
facial weakness (hemiparesis improved but
did not resolve by 12-mo postoperative visit)
Multiple seizures/generalized
CPS
CPS
R
L
R
Microdysgenesis
Cortical dysplasia
Cortical dysplasia
Cortical dysplasia
No neurological impairment
Contralateral hemiplegia, aphasia
Contralateral hemiparesis, contralateral facial
weakness
Contralateral hemiparesis (improved but
did not resolve by 12-mo postoperative
examination)
L
L
Nonspecific changes
Cortical dysplasia
No neurological impairment
Contralateral hemiparesis, contralateral facial
weakness (improved but did not resolve at
12-mo postoperative examination)
Nonspecific changes
L
L
R
R
R
R
Cortical dysplasia
Cortical dysplasia
Cortical dysplasia
Meningioangiomatosis
Cortical dysplasia
Cortical dysplasia
CPS
CPS
CPS
Multiple seizures/generalized
SPS
CPS
SPS
SPS-secondary generalized
SPS
SPS
SPS
SPS
CPS-secondary generalized
No neurological impairment
(Continues)
1
2
3
4
5
6
Pathology
Cortical dysplasia
Cortical dysplasia
No neurological impairment
Contralateral hemiparesis, facial weakness,
aphasia
resolution of symptoms between 1 week and 1 month postoperatively, and 3 had their SMA syndrome resolve beyond 1
month after surgery. The resolution of SMA syndrome was not
statistically associated with the age at seizure onset, age at time of
surgery, delay between seizure identification and surgery, sex,
handedness, seizure type, use of invasive monitoring, surgery type,
pathologic diagnosis, or preoperative MRI finding of lesion
(Table 4). Of note, a single patient developed SMA syndrome
after surgery for placement of subdural grid and strip electrodes,
not after surgical resection. This patient developed contralateral
hemiplegia and mild expressive aphasia shortly after surgery.
Motor and speech impairment gradually improved with complete
resolution by 1 week postoperatively.
AVM, arteriovenous malformation; CPS, complex partial seizures; SPS, simple partial seizures.
L
L
CPS-secondary generalized
Multiple seizures/generalized
R
R
132
123
38
39
M
F
F
M
Age at Surgery,
mo
Sex Handedness
Patient
TABLE 3. Continued
Seizure Type
Side of
Surgery
Pathology
Immediate Postoperative
Neurological Impairment
KASASBEH ET AL
Seizure Outcome
Seizure outcomes as determined by Engel classification40 at
12 months and extended follow-up visits are summarized in
Tables 5 and 6. At 12 month postoperatively, 31 of 37 patients
(84%) had Engel class I or II, and 6 patients (16%) had Engel
class III or IV. Seizure outcome at 12 months postoperatively was
not found to be significantly associated with age at seizure
identification, age at time of surgery, delay between seizure
identification and surgery, sex, handedness, seizure type, use of
invasive monitoring, preoperative MRI identification of lesion,
surgery type, or pathology identified. With regard to surgery type,
lesionectomy had been performed in 8 patients (26%) found to
have Engel class I/II, whereas no patient with Engel class III/IV
had undergone lesionectomy. A Fisher exact test did not
demonstrate a statistically significant relationship between seizure
outcome and type of surgery performed (P = .31).
At extended follow-up, 16 of 22 patients (73%) had Engel class
I/II, whereas 6 patients (27%) had Engel class III/IV. Age at the
time of surgery was 173 6 38 months for patients with Engel class
I/II and 98.9 6 64 months for patients with Engel class III/IV,
significantly longer in patients with favorable seizure outcome
(P = .02). Moreover, the delay between seizure onset and
surgery was significantly longer (P = .05) in patients with Engel
class I/II (108 6 67 months) compared with patients with Engel
class III/IV (45.0 6 25 months). With regard to surgery type,
lesionectomy was performed in 4 patients (25%) found to have
Engel class I/II, whereas 1 patient (17%) with Engel class III/IV
had lesionectomy performed. Seizure outcome at the last followup was not significantly associated with age at seizure identification, sex, handedness, seizure type, use of invasive monitoring,
preoperative MRI identification of lesion, surgery type, or
pathological diagnosis.
Changes in seizure outcome between 1 month and each
subsequent visit were analyzed. The majority of patients maintained the same outcome at 1 month with no decline in Engel class
throughout the follow-up period; 87% at 6 months, 81% at 12
months, 70% at 24 months, and 64% at the last follow-up
maintained the same seizure outcome as at 1-month. The
proportion of patients who had a decline in seizure outcome
www.neurosurgery-online.com
.31
.60
.07
.78
.72
.52
.93
.05
.42
.08
89.0 6 48
152 6 44
63.3 6 46
3 (50)
2/4 (50)
1 (17)
5 (83)
3 (50)
2 (33)
3 (50)
27.0 6 39
177 6 27
150 6 64
1 (33)
3 (100)
0
3 (100)
1 (33)
0
0
Engel Class
I
II
III
IV
76.3 6 46
169 6 17
92.1 6 45
2 (29)
5 (71)
2 (29)
6 (86)
2 (29)
1 (14)
6 (86)
57.6 6 58
126 6 68
62.7 6 60
9 (56)
9/14 (64)
5 (31)
14 (88)
10 (62)
5 (31)
10/15 (67)
Age of seizure onset, mo
Age at surgery, mo
Time between seizure onset and surgery, mo
Female sex, n (%)
Right handedness, n/N (%)
Seizure type, secondary generalized, n (%)
Invasive monitoring, n (%)
Preoperative MRI, lesional, n (%)
Surgery type, lesionectomy, n (%)
Pathology, forms of dysplasia, n/N (%)
NEUROSURGERY
At 12 mo
(n = 37)
25
6
4
2
(68)
(16)
(11)
(5)
At Extended
Follow-up (n = 22)
12
4
5
1
(55)
(18)
(23)
(5)
46.3 6 33
148 6 65
103 6 68
4 (57)
5/6 (83)
0
7 (100)
0
0
6 (86)
Permanent
Impairment (n = 6)
Resolved After
1 mo (n = 3)
Resolved by
1 wk (n = 7)
Resolved Between
1 wk and 1 mo (n = 7)
No Impairment
(n = 16)
Variable
Neurological Deficit
TABLE 4. Neurological Impairment After Surgery in the Medial Frontal Lobe and Resolution of Supplementary Motor Area Syndromea
KASASBEH ET AL
Variable
I/II (n = 31)
III/IV (n = 6)
I/II (n = 16)
III/IV (n = 6)
61.7 6 52
149 6 60
85.5 6 64
17 (55)
21/27 (78)
6 (19)
27 (87)
14 (45)
8 (26)
22 (71)
48.0 6 36
128 6 43
79.8 6 50
2 (33)
3 (50)
1 (17)
6 (100)
2 (33)
0
3 (50)
.78
.18
.95
.40
.31
1.0
1.0
.68
.31
.37
65.3 6 53
173 6 38
108 6 67
6 (38)
10/13 (77)
2 (12)
14 (88)
7 (44)
4 (25)
10 (62)
53.5 6 63
98.9 6 64
45.0 6 25
4 (67)
4 (67)
0
6 (100)
3 (50)
1 (17)
1 (17)
.44
.02
.05
.35
1.0
1.0
1.0
1.0
1.0
.15
CPS, complex partial seizures; MRI, magnetic resonance imaging; SPS, simple partial seizures.
TABLE 7. Association Between Early Postoperative Seizure Recurrence and Follow-up Engel Class Categories
Early Postoperative Seizure Recurrence (1 Month), n (%)
Follow-up
6 mo
12 mo
Extended follow-up
Seizure Outcome
Seizure recurrence
Seizure freedom
Engel III/IV
Engel I/II
Seizure recurrence
Seizure freedom
Engel III/IV
Engel I/II
Seizure recurrence
Seizure freedom
Engel III/IV
Engel I/II
9 (100)
0
5 (56)
4 (44)
8 (100)
0
3 (38)
5 (62)
4 (100)
0
1 (25)
3 (75)
Seizure Freedom
6
24
3
27
10
19
3
26
9
9
5
13
(20)
(80)
(10)
(90)
(34)
(66)
(10)
(90)
(50)
(50)
(28)
(72)
P
,.001
.009
.001
.10
.12
1.0
www.neurosurgery-online.com
TABLE 8. Association Between Extent and Location of Resection With Patient Characteristics and Seizure Outcomea
Extent and Location of Resection
Variable
Age of seizure onset (n = 34)
r
P
Age at surgery (n = 34)
r
P
Time between seizure onset and
surgery (n = 34)
r
P
Sex
Female (n = 16)
Male (n = 18)
P
Handedness
Left (n = 8)
Right (n = 21)
P
Pathology
Forms of dysplasia (n = 22)
Other (n = 11)
P
Engel class, 12- mo follow-up
I/II (n = 27)
III/IV (n = 5)
P
Engel class, extended follow-up
I/II (n = 13)
III/IV (n = 5)
P
Distance
Anterior to
Precentral
Sulcus, cm
Distance
Superior to
Cingulate
Gyrus
Distance
Lateral to
Fissure
Anteroposterior
Extent of
Resection
Superior-inferior
Extent of
Resection
Transverse
Extent of
Resection
20.23
.19
20.12
.48
20.01
.95
0.09
.62
20.30
.09
20.18
.32
20.12
.50
0.10
.56
.20.03
.88
0.04
.83
20.04
.80
20.24
.17
0.04
.82
0.06
.72
0.12
.50
0.11
.52
0.21
.24
20.10
.56
0.00 (0, 0)
0.00 (0, 0)
1.0
a
For continuous characteristics, data are Spearman correlation (r) with associated P value. For categorical characteristics, data are median (25th, 75th percentile) for the
distances where P values compare the distances across characteristic subgroups by the Wilcoxon test. Values in parentheses are 25th and 75th percentiles when appropriate.
NEUROSURGERY
KASASBEH ET AL
FIGURE 1. In each intraoperative photo, note that the operative field is oriented as indicated in A. A, intraoperative picture
demonstrating placement of left frontal cortical array. B, intraoperative picture demonstrating motor (M) and sensory (S) cortex.
C, intraoperative image demonstrating resection of the left frontal seizure focus in the supplementary motor cortex. D, plain skull
radiograph demonstrating placement of subdural grids and strips.
www.neurosurgery-online.com
FIGURE 2. In each intraoperative photo, note that the operative field is oriented as indicated in A. A, intraoperative picture
demonstrating placement of right frontal and parietal cortical array. B, intraoperative picture demonstrating motor cortex
representing hand control (H). C, intraoperative image demonstrating resection of the right frontal seizure focus in the supplementary motor cortex. D, plain skull radiograph demonstrating placement of subdural grids and strips in the patients index
operation.
DISCUSSION
SMA Anatomy and Function
First described by Penfield and colleagues,44-47 the SMA
comprises a distinct anatomic and functional region of the
cerebral cortex situated largely on the mesial aspect of the superior
frontal gyrus.46 The SMA is limited posteriorly by the precentral
sulcus and inferiorly by the cingulate sulcus and genu of corpus
callosum.46-49 The anterior and lateral borders are less definite.
Early cortical stimulation studies indicated that the SMA extends
up to 5 cm anterior to the precentral sulcus and laterally to the
superior frontal sulcus.49 More recent studies suggest that
the posterior, lateral, and anterior margins may be variable.50
The SMA is considered to be composed of 2 distinct areas:
a caudal SMA proper or F3, which projects directly to primary
motor cortex and to spinal cord, and a rostral pre-SMA or F6,
which receives projections from the prefrontal cortex and
NEUROSURGERY
KASASBEH ET AL
www.neurosurgery-online.com
NEUROSURGERY
TABLE 9. Previous Reports of Supplementary Motor Area Syndrome After Surgical Resection of Mesial Frontal Lobea
Study (Year)
Patients
(Pediatric
Patients
and (age), n
Patient
Presentation
Underlying
Pathology (n)
Developed
SMA
Syndrome, %
Developed Other
Neurological
Complications, %
3 (0)
Seizures
100
N/A
Rostomily
et al36
(1991)
6 (0)
Seizures, hemiparesis,
speech impairment
Low-grade astrocytoma
(4), anaplastic
astrocytoma (1),
metastatic breast
adenocarcinoma (1)
100
N/A
Bleasel et al29
(1996)
10 (2; ages
13, 14)
Seizures
60
N/A
Zentner
et al39
(1996)
28 (0)
89
Bannur and
Rajshekhar28
(2000)
6 (0)
100
Duffau et al30
(2001)
1 (0)
Seizures
Low-grade glioma
100
Seizure Control
After Epilepsy
Patient 1: significant
impairment up to 15
mo; patient 2: returned
to normal at 1-mo
follow-up; patient 3: was
normal at 8-mo followup
Motor function returned
to near-baseline level 4
to 8 wk postoperatively;
restriction of
spontaneous movement
resolved after several
more weeks; at 6 mo
postoperatively,
patients had returned to
baseline function
Patients returned to
baseline in 2 d-2 mo
N/A
N/A
N/A
Laplane et al33
(1977)
Duration of Recovery
From SMA Syndrome
Study (Year)
www.neurosurgery-online.com
Patients
(Pediatric
Patients
and (age), n
Patient
Presentation
Underlying
Pathology (n)
Developed
SMA
Syndrome, %
Developed Other
Neurological
Complications, %
65
N/A
100
N/A
Krainik et al32
(2001)
23 (0)
Seizures
Fontaine et al31
(2002)
11 (0)
Seizures, headache
Peraud et al34
(2002)
24 (0)
Seizures, speech
disturbances, motor
impairment,
headache, memory
deficits
83
Russell and
Kelly37 (2003)
27 (0)
Seizures, hemiparesis,
headache
26
Ulu et al38
(2008)
12 (3; ages
10, 11,
and 14 y)
50
N/A
Rosenberg
et al35 (2010)
26 (0)
Seizures (4 patients
Low- and high-grade
underwent surgery for
tumors (9),
medically intractable
nontumorous
epilepsy), hemiparesis
lesions (3)
Seizures, motor and
High- and low-grade
speech impairment
gliomas, metastatic
lesions, cavernoma,
cortical dysplasia,
meningioma
23.1
N/A
Duration of Recovery
From SMA Syndrome
Seizure Control
After Epilepsy
N/A
N/A
N/A
KASASBEH ET AL
TABLE 9. Continued
deficit is most likely SMA syndrome, and the prognosis for motor
recovery is excellent. Should the cortical stimulation threshold be
significantly increased or responses no longer obtained or if
resection involves the primary motor cortex, a permanent deficit
is more likely the outcome. Nevertheless, substantial improvement is generally the rule (Table 3).
We have observed 2 predominant patterns of recovery in our
patients. Those that ultimately go on to have SMA syndrome
without permanent deficit may have a profound hemiplegia with
neglect in the first hours or days after surgery and recovery of
movement in distal extremities (finger and toe fine movements)
first. Patients with permanent deficits regain proximal movement
first, consistent with pyramidal/corticospinal tract injury. Thus,
a patient with an intact cortical stimulation threshold at the
completion of resection who recovers some finger movement in
the first week most likely has pure SMA syndrome with an
excellent prognosis for recovery. Our 6 patients with residual
permanent deficits demonstrated little improvement before
discharge from the hospital. In those who showed some recovery
before discharge, improvement in proximal movement was
often noted.
Berger et al86 reported that resections within 1 cm of eloquent
cortex have a substantially increased risk of irreversible deficit. We
have found that resections in the SMA region, within 1 cm of the
precentral gyrus, also have the highest rate of postoperative deficit
(Table 2). However, careful preservation of the precentral gyrus
with a subpial aspiration technique back to the precentral sulcus
can result in excellent outcomes with no deficit once the SMA
syndrome resolves. Care should be taken not to undercut the
white matter of the precentral gyrus, and frequent subcortical
mapping during the resection can help ensure the integrity of the
descending tracts of the primary motor areas. For patients who
developed permanent neurological deficit in our series, distances
of resection from precentral sulcus and cingulate gyrus were
significantly shorter compared with those in patients with no
neurological impairment. Moreover, there was a trend toward
larger anteroposterior dimension of resection in patients who
developed permanent impairment. In none of the patients who
developed permanent deficit was the primary motor cortex
knowingly resected. Further studies investigating the development of permanent deficit after resection of the SMA proper vs
pre-SMA are warranted.
Neurological Recovery
The transitory nature of neurological impairment is the
hallmark of SMA syndrome. Of the 17 patients in this study
who developed SMA syndrome, 7 (41%) had resolution of
symptoms by 1 week postoperatively, 7 (41%) had resolution of
symptoms between the 1-week and 1-month follow-up visits, and
3 (18%) had resolution of symptoms after the 1-month follow-up
visit. The rate of resolution of SMA syndrome was not found to
significantly correlate with patient characteristics, seizure characteristics, use of invasive monitoring, or surgery type. Interestingly,
NEUROSURGERY
KASASBEH ET AL
addition to the residual activity of an oscillatory loop, with longterm recovery attributed to long-term plasticity.30 In the
developing brain, plasticity is undoubtedly an important contributing factor in resolution of SMA syndrome in pediatric
patients.94-96 Future studies elucidating the precise underlying
mechanisms of resolution of SMA syndrome are needed to
validate these hypotheses.
Seizure Outcome
The majority of patients had favorable seizure outcome (Engel
class I or II) at the 12-month and extended follow-up visits (84%
and 73%, respectively). Lesionectomy was performed in 26% of
patients with Engel class I/II at the 12-month postoperative
follow-up, whereas none of the patients who had Engel class III/IV
had lesionectomy. Similarly, at the last follow-up, more patients
with Engel class I/II were found to have undergone lesionectomy.
These findings notwithstanding, our analysis did not demonstrate
a statistically significant relationship between seizure outcome and
type of surgery performed. The absence of statistical significance
compared with patients who underwent other surgical procedures
may be explained by the fact that a large proportion of patients who
did not undergo lesionectomies also had favorable seizure outcome. In addition, the small number of patients who underwent
lesionectomies may have precluded statistical significance. Of
note, age at the time of surgery was significantly higher for patients
with Engel class I/II compared with patients with Engel class
III/IV at the extended follow-up. Furthermore, at the extended
follow-up, the delay between seizure identification and surgery was
significantly longer in patients with Engel class I/II compared with
patients with Engel class III/IV. These findings are not explained
by our data collection but may be related to the underlying cause of
seizure disorder in younger vs older patients undergoing epilepsy
surgery.
Seizure outcome in the early postoperative period remained
largely unchanged throughout the follow-up period. More
extensive anteroposterior extent of surgical resection was found
to be associated with an appreciable, albeit statistically insignificant, decline in Engel class between the 1- and 6-month follow-up
visits. Similarly, a decline was found between the 1-month and
12-month follow-up visits in the proximity of the posterior border
of the surgical resection to precentral sulcus. Additionally, a decline
in Engel class was noted with more extensive superior-inferior
resections. Of note, the number of patients who experienced
deterioration in seizure outcome after the first month postoperatively was small (n = 4-6). This may explain the absence
of statistical significance in our studies. Moreover, the variability
in Engel class changes was not sufficient to allow further statistical
analyses. In addition, early postoperative seizure recurrence was
associated with a significantly increased likelihood of seizures at
the 6-month and 12-month follow-up visits and a nonsignificant
trend toward seizure recurrence at extended follow-up visit.
These findings indicate that early seizure recurrence is a negative
predictor of seizure outcome. Long-term seizure control did
not correlate with dimensions of surgical resection, with the
CONCLUSION
Surgery in the region of the medial frontal cortex is associated
with the development of SMA syndrome. In this study of
exclusively pediatric patients, fewer than half of the patients
developed SMA syndrome. The SMA syndrome was characterized
primarily by postoperative contralateral hemiparesis/hemiplegia
that developed within hours of surgery and resolved in the majority
of cases by 1 month postoperatively. Development of postoperative SMA syndrome was related to the anteroposterior extent
of surgical resection and proximity of the resection to the
precentral and cingulate sulci. In addition, surgery in the medial
frontal lobe was associated with favorable seizure outcomes. Our
studies show that resections in the SMA can be performed safely
in children and are associated with reversible neurological
impairment.
Disclosure
The authors have no personal financial or institutional interest in any of the
drugs, materials, or devices described in this article.
REFERENCES
1. Hauser WA, Hesdorffer DC. Epilepsy: Frequency, Causes and Consequences.
New York, NY: Demos; 1990.
2. Berg AT. The epidemiology of seizures and epilepsy in children. In: Shinnar S,
Amir N, Branski D, eds. Childhood Seizures. Basel, Switzerland: Karger; 1995:1-10.
3. Shinnar S, Pellock JM. Update on the epidemiology and prognosis of pediatric
epilepsy. J Child Neurol. 2002;17(suppl 1):S4-S17.
4. Caplan R, Siddarth P, Vona P, et al. Language in pediatric epilepsy. Epilepsia.
2009;50(11):2397-2407.
5. Bailet LL, Turk WR. The impact of childhood epilepsy on neurocognitive and
behavioral performance: a prospective longitudinal study. Epilepsia. 2000;41(4):
426-431.
6. Bjornaes H, Stabell K, Henriksen O, Loyning Y. The effects of refractory epilepsy
on intellectual functioning in children and adults; a longitudinal study. Seizure.
2001;10(4):250-259.
7. Tromp SC, Weber JW, Aldenkamp AP, Arends J, vander Linden I, Diepman L.
Relative influence of epileptic seizures and of epilepsy syndrome on cognitive
function. J Child Neurol. 2003;18(6):407-412.
8. van Empelen R, Jennekens-Schinkel A, van Rijen PC, Helders PJ, van
Nieuwenhuizen O. Health-related quality of life and self-perceived competence
of children assessed before and up to two years after epilepsy surgery. Epilepsia.
2005;46(2):258-271.
9. Hum KM, Smith ML, Lach L, Elliott IM. Self-perceptions of social function 2
years after pediatric epilepsy surgery. Epilepsy Behav. 2010;17(3):354-359.
10. Nashef L, Fish DR, Garner S, Sander JW, Shorvon SD. Sudden death in epilepsy:
a study of incidence in a young cohort with epilepsy and learning difficulty.
Epilepsia. 1995;36(12):1187-1194.
www.neurosurgery-online.com
11. Callenbach PM, Westendorp RG, Geerts AT, et al. Mortality risk in children with
epilepsy: the Dutch study of epilepsy in childhood. Pediatrics. 2001;107(6):
1259-1263.
12. Breningstall GN. Mortality in pediatric epilepsy. Pediatr Neurol. 2001;25(1):9-16.
13. Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk
of relapse after a first unprovoked tonic-clonic seizure: First Seizure Trial Group
(FIR.S.T. Group). Neurology. 1993;43(3 pt 1):478-483.
14. Musicco M, Beghi E, Solari A, Viani F. Treatment of first tonic-clonic seizure does
not improve the prognosis of epilepsy: First Seizure Trial Group (FIRST Group).
Neurology. 1997;49(4):991-998.
15. Shinnar S, Berg AT, ODell C, Newstein D, Moshe SL, Hauser WA. Predictors of
multiple seizures in a cohort of children prospectively followed from the time of
their first unprovoked seizure. Ann Neurol. 2000;48(2):140-147.
16. Hadjiloizou SM, Bourgeois BF. Antiepileptic drug treatment in children. Expert
Rev Neurother. 2007;7(2):179-193.
17. Shinnar S, Berg AT. Does antiepileptic drug therapy prevent the development of
chronic epilepsy? Epilepsia. 1996;37(8):701-708.
18. Arts WF, Visser LH, Loonen MC, et al. Follow-up of 146 children with epilepsy
after withdrawal of antiepileptic therapy. Epilepsia. 1988;29(3):244-250.
19. Shinnar S, Berg AT, Moshe SL, et al. Discontinuing antiepileptic drugs in children
with epilepsy: a prospective study. Ann Neurol. 1994;35(5):534-545.
20. Tennison M, Greenwood R, Lewis D, Thorn M. Discontinuing antiepileptic
drugs in children with epilepsy: a comparison of a six-week and a nine-month taper
period. N Engl J Med. 1994;330(20):1407-1410.
21. Sillanpaa M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with
onset in childhood. N Engl J Med. 1998;338(24):1715-1722.
22. Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. Early
development of intractable epilepsy in children: a prospective study. Neurology.
2001;56(11):1445-1452.
23. Berg AT, Shinnar S, Levy SR, et al. Defining early seizure outcomes in pediatric
epilepsy: the good, the bad and the in-between. Epilepsy Res. 2001;43(1):75-84.
24. Sillanpaa M, Jalava M, Shinnar S. Epilepsy syndromes in patients with childhoodonset seizures in Finland. Pediatr Neurol. 1999;21(2):533-537.
25. Behrens E, Schramm J, Zentner J, Konig R. Surgical and neurological complications
in a series of 708 epilepsy surgery procedures. Neurosurgery. 1997;41(1):1-9.
26. Dorward IG, Titus JB, Limbrick DD, Johnston JM, Bertrand ME, Smyth MD.
Extratemporal, nonlesional epilepsy in children: postsurgical clinical and neurocognitive outcomes. J Neurosurg Pediatr. 2011;7(2):179-188.
27. Hemb M, Velasco TR, Parnes MS, et al. Improved outcomes in pediatric epilepsy
surgery: the UCLA experience, 1986-2008. Neurology. 2010;74(22):1768-1775.
28. Bannur U, Rajshekhar V. Post operative supplementary motor area syndrome:
clinical features and outcome. Br J Neurosurg. 2000;14(3):204-210.
29. Bleasel A, Comair Y, Luders H. Surgical ablations of the mesial frontal lobe in
humans. Adv Neurol. 1996;70:217-235.
30. Duffau H, Lopes M, Denvil D, Capelle L. Delayed onset of the supplementary
motor area syndrome after surgical resection of the mesial frontal lobe: a time
course study using intraoperative mapping in an awake patient. Stereotact Funct
Neurosurg. 2001;76(2):74-82.
31. Fontaine D, Capelle L, Duffau H. Somatotopy of the supplementary motor area:
evidence from correlation of the extent of surgical resection with the clinical
patterns of deficit. Neurosurgery. 2002;50(2):297-303.
32. Krainik A, Lehericy S, Duffau H, et al. Role of the supplementary motor area in
motor deficit following medial frontal lobe surgery. Neurology. 2001;57(5):871-878.
33. Laplane D, Talairach J, Meininger V, Bancaud J, Orgogozo JM. Clinical
consequences of corticectomies involving the supplementary motor area in man.
J Neurol Sci. 1977;34(3):301-314.
34. Peraud A, Meschede M, Eisner W, Ilmberger J, Reulen HJ. Surgical resection of
grade II astrocytomas in the superior frontal gyrus. Neurosurgery. 2002;50(5):
966-975.
35. Rosenberg K, Nossek E, Liebling R, et al. Prediction of neurological deficits and
recovery after surgery in the supplementary motor area: a prospective study in 26
patients. J Neurosurg. 2010;113(6):1152-1163.
36. Rostomily RC, Berger MS, Ojemann GA, Lettich E. Postoperative deficits and
functional recovery following removal of tumors involving the dominant hemisphere supplementary motor area. J Neurosurg. 1991;75(1):62-68.
37. Russell SM, Kelly PJ. Incidence and clinical evolution of postoperative deficits after
volumetric stereotactic resection of glial neoplasms involving the supplementary
motor area. Neurosurgery. 2003;52(3):506-516.
NEUROSURGERY
38. Ulu MO, Tanriover N, Ozlen F, et al. Surgical treatment of lesions involving the
supplementary motor area: clinical results of 12 patients. Turk Neurosurg. 2008;18
(3):286-293.
39. Zentner J, Hufnagel A, Pechstein U, Wolf HK, Schramm J. Functional results
after resective procedures involving the supplementary motor area. J Neurosurg.
1996;85(4):542-549.
40. Engel JJ, Van Ness PC, Rasmussen TB, Ojemann LM. Surgical treatment of the
epilepsies. In: Engel JJ, ed. Outcome With Respect to Epileptic Seizures. New York,
NY: Raven Press; 1993:609-621.
41. Sanai N, Berger MS. Intraoperative stimulation techniques for functional pathway
preservation and glioma resection. Neurosurg Focus. 2010;28(2):E1.
42. Keles GE, Lundin DA, Lamborn KR, Chang EF, Ojemann G, Berger MS.
Intraoperative subcortical stimulation mapping for hemispherical perirolandic
gliomas located within or adjacent to the descending motor pathways: evaluation
of morbidity and assessment of functional outcome in 294 patients. J Neurosurg.
2004;100(3):369-375.
43. Ojemann SG, Berger MS, Lettich E, Ojemann GA. Localization of language
function in children: results of electrical stimulation mapping. J Neurosurg. 2003;
98(3):465-470.
44. Penfield W, Roberts L. Speech and Brain Mechanisms. Princeton, NJ: Princeton
University Press; 1959.
45. Penfield W. The supplementary motor area in the cerebral cortex of man. Arch
Psychiatr Nervenkr Z Gesamte Neurol Psychiatr. 1950;185(6-7):670-674.
46. Penfield W, Welch K. The supplementary motor area of the cerebral cortex;
a clinical and experimental study. AMA Arch Neurol Psychiatry. 1951;66(3):289-317.
47. Penfield W, Rasmussen T. The Cerebral Cortex of Man: a Clinical Study of
Localization of Function. New York, NY: Macmillan; 1950.
48. Picard N, Strick PL. Motor areas of the medial wall: a review of their location and
functional activation. Cereb Cortex. 1996;6(3):342-353.
49. Talairach J, Bancaud J. The supplementary motor area in man (anatomofunctional
findings by stereo-electroencephalography in epilepsy). Int J Neurol. 1966;5:
330-347.
50. Lim SH, Dinner DS, Pillay PK, et al. Functional anatomy of the human
supplementary sensorimotor area: results of extraoperative electrical stimulation.
Electroencephalogr Clin Neurophysiol. 1994;91(3):179-193.
51. Tanji J. The supplementary motor area in the cerebral cortex. Neurosci Res. 1994;
19(3):251-268.
52. Hutchins KD, Martino AM, Strick PL. Corticospinal projections from the medial
wall of the hemisphere. Exp Brain Res. 1988;71(3):667-672.
53. Jurgens U. The efferent and afferent connections of the supplementary motor area.
Brain Res. 1984;300(1):63-81.
54. Macpherson J, Wiesendanger M, Marangoz C, Miles TS. Corticospinal neurones
of the supplementary motor area of monkeys: a single unit study. Exp Brain Res.
1982;48(1):81-88.
55. Schell GR, Strick PL. The origin of thalamic inputs to the arcuate premotor and
supplementary motor areas. J Neurosci. 1984;4(2):539-560.
56. Wiesendanger M, Wiesendanger R. The supplementary motor area in the light of
recent investigations. Exp Brain Res Suppl. 1984;9:382-392.
57. Wiesendanger M. Recent developments in studies of the supplementary motor
area of primates. Rev Physiol Biochem Pharmacol. 1986;103:1-59.
58. Eccles JC. The initiation of voluntary movements by the supplementary motor
area. Arch Psychiatr Nervenkr. 1982;231(5):423-441.
59. Green JR, Angevine JB, White JC Jr, Edes AD, Smith RD. Significance of the
supplementary motor area in partial seizures and in cerebral localization.
Neurosurgery. 1980;6(1):66-75.
60. Morris HH III, Dinner DS, Luders H, Wyllie E, Kramer R. Supplementary motor
seizures: clinical and electroencephalographic findings. Neurology. 1988;38(7):
1075-1082.
61. Penfield W, Jasper H. Epilepsy and the Functional Anatomy of the Human Brain.
Boston, MA: Little, Brown and Co; 1954.
62. Woolsey CN, Erickson TC, Gilson WE. Localization in somatic sensory and
motor areas of human cerebral cortex as determined by direct recording of evoked
potentials and electrical stimulation. J Neurosurg. 1979;51(4):476-506.
63. Mushiake H, Inase M, Tanji J. Neuronal activity in the primate premotor,
supplementary, and precentral motor cortex during visually guided and internally
determined sequential movements. J Neurophysiol. 1991;66(3):705-718.
64. Tanji J, Shima K. Role for supplementary motor area cells in planning several
movements ahead. Nature. 1994;371(6496):413-416.
KASASBEH ET AL
88. von Lehe M, Schramm J. Gliomas of the cingulate gyrus: surgical management and
functional outcome. Neurosurg Focus. 2009;27(2):E9.
89. Freund HJ. Premotor areas in man. Trends Neurosci. 1984;7(12):481-483.
90. Krainik A, Lehericy S, Duffau H, et al. Postoperative speech disorder after medial
frontal surgery: role of the supplementary motor area. Neurology. 2003;60(4):
587-594.
91. Krainik A, Duffau H, Capelle L, et al. Role of the healthy hemisphere in recovery
after resection of the supplementary motor area. Neurology. 2004;62(8):1323-1332.
92. Freund HJ. Premotor area and preparation of movement. Rev Neurol (Paris). 1990;
146(10):543-547.
93. Aizawa H, Inase M, Mushiake H, Shima K, Tanji J. Reorganization of activity in
the supplementary motor area associated with motor learning and functional
recovery. Exp Brain Res. 1991;84(3):668-671.
94. Johnston MV, Ishida A, Ishida WN, Matsushita HB, Nishimura A, Tsuji M.
Plasticity and injury in the developing brain. Brain Dev. 2009;31(1):1-10.
95. Johnston MV, Nishimura A, Harum K, Pekar J, Blue ME. Sculpting the
developing brain. Adv Pediatr. 2001;48:1-38.
96. Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human
cerebral cortex. J Comp Neurol. 1997;387(2):167-178.
COMMENT
www.neurosurgery-online.com