characterization of the supplementary motor area syndrome and seizure outcome after medial frontal...

8/10/2019 Characterization of the Supplementary Motor Area Syndrome and Seizure Outcome After Medial Frontal Lobe Rese

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Characterization of the Supplementary Motor AreaSyndrome and Seizure Outcome After MedialFrontal Lobe Resections in PediatricEpilepsy Surgery

BACKGROUND: In adults, resection of the medial frontal lobe has been shown to resultin supplementary motor area (SMA) syndrome, a disorder characterized by transientmotor impairment. Studies examining the development of SMA syndrome in children,however, are wanting.OBJECTIVE: To characterize the development of SMA syndrome and to analyze seizureoutcomes after surgery in the medial frontal lobe for medically intractable epilepsy.METHODS: Thirty-nine patients with medically intractable epilepsy who underwent

surgery in the medial frontal lobe were reviewed retrospectively. The progression ofneurological impairment and seizure outcome after surgery was recorded, and theextent of cortex resected was analyzed.RESULTS: After resection in the region of the SMA, 23 patients (59%) developedpostoperative neurological impairment; 17 (74%) were identified as SMA syndrome. Noneurological impairment was found after surgery in 16 patients (41%). Six patients (15%)experienced permanent neurological impairment. The majority of patients (82%) whodeveloped SMA syndrome had resolution of their symptoms by 1 month postopera-tively. Preoperative magnetic resonance imaging finding of lesional cases was asso-ciated with a significantly decreased likelihood of developing SMA syndrome (P= .02).Seizure outcome was favorable after surgery in most patients.CONCLUSION: Surgery for medically intractable epilepsy in the region of the medial

frontal cortex is effective and associated with reversible neurological impairment inchildren. All patients had resolution of their SMA syndrome by 6 months postoperatively.

KEY WORDS: Epilepsy surgery, Pediatric epilepsy, Supplementary motor area

Neurosurgery 70:11521168, 2012 DOI: 10.1227/NEU.0b013e31823f6001 www.neurosurgery-online.com

Epilepsy is a common neurological disorderaffecting approximately 1% of children,and nearly 40% of all newly recognized

cases of epilepsy are diagnosed during child-hood.1-3 Pediatric epilepsy is associated withconsiderable neurocognitive, behavioral, and

developmental impairment4-7

; impairment inquality of life8,9; and increased mortality.10-12

These factors underscore the necessity of propertreatment of epilepsy in childhood.

Treatment of pediatric epilepsy remainschallenging and demands a multidisciplinary

approach. Antiepileptic drugs reduce the recur-rence of seizures13-15 but demonstrate consider-able, and often restricting, side effects,16 andtheir role in affecting long-term remission isquestionable.14,17 Moreover, a significant pro-portion of patients who are seizure free on

medications relapse after discontinuation ofantiepileptic drug treatment,18-20 and a subsetof patients continue to experience debilitatingseizures despite maximal medical treatment.21-24

For such patients with medically intractableepilepsy, surgery is often considered for success-ful multimodal treatment directed at controllingseizures and averting developmental delay.

Surgical complications of epilepsy surgery havebeen declining with increased experience and

Aimen S. Kasasbeh, MD*

Chester K. Yarbrough, MD

David D. Limbrick, MD, PhD

Karen Steger-May, MA

James L. Leach, MDk

Francesco T. Mangano, DO

Matthew D. Smyth, MD

*Department of Neuroscience, University

of Arizona, Tucson, Arizona; Depart-

ment of Neurological Surgery, Saint Louis

Childrens Hospital and; Division of

Biostatistics, Washington University

School of Medicine in St. Louis, St. Louis,

Missouri; kDepartment of Medical Imag-

ing and Department of Neurological

Surgery, Cincinnati Childrens Hospital

Medical Center, Cincinnati, Ohio

Correspondence:

Aimen S. Kasasbeh, MD,

Department of Neuroscience,University of Arizona,

1548 E Drachman St, PO Box 210476,

Tucson, AZ 85719.

E-mail: [email protected]

Received,June 17, 2011.

Accepted,October 15, 2011.

Published Online, November 23, 2011.

Copyright 2011 by the

Congress of Neurological Surgeons

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ABBREVIATIONS: SMA, supplementary motorarea;video-EEG, video electroencephalography

RESEARCHHUMANCLINICAL STUDIES

TOPIC RESEARCHHUMANCLINICAL STUDIES

1152 | VOLUME 70 | NUMBER 5 | MAY 2012 www.neurosurgery-online.com

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.


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improved diagnostic and surgical techniques.25-27 Surgical resec-tion 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 transientneurological condition known as SMA syndrome.28-39 Firstdescribed after surgical resection by Laplane et al,33 the syndrome

has a strikingly consistent clinical evolution postoperatively,characterized by transient hemiparesis or motor apraxia withvariable degrees of speech arrest followed by rapid recovery ofneurological impairment.

We examined the development of SMA syndrome in a series of39 children who underwent surgery for resection of a seizure focusin the medial frontal cortex. In addition, we analyzed seizureoutcomes after surgery. To the best of our knowledge, this reportrepresents the largest study of SMA syndrome after surgery in themedial frontal lobe and is the first to be done in an exclusivelypediatric patient population.

METHODSPatient Population and Preoperative Evaluation

After Institutional Review Board approval was granted at the St. LouisChildrens Hospital/Washington University in St. Louis HumanResearch Program and Cincinnati Childrens Hospital Medical Center,medical records of patients who underwent surgical management formedically intractable epilepsy between 1994 and 2010 were reviewed.Patients with resections in the medial frontal lobe were included in thestudy. Table 1 summarizes the patient and seizure characteristics of39 patients who met these inclusion criteria. Preoperative evaluation wastailored for each patient and included magnetic resonance imaging

(MRI), functional MRI, video electroencephalography (video-EEG),brain positron emission tomography, magnetoencephalography, single-photon emission computed tomography, subtraction ictal single-photonemission computed tomography coregistered to MRI, Wada testing,cerebral angiogram, and neuropsychological evaluation. All but 4patients underwent invasive monitoring. All evaluation studies werediscussed by a multidisciplinary epilepsy team including pediatricneurosurgeons, pediatric epileptologists, neuroradiologists, neuropsy-chologists, EEG technologists, and support personnel.

Study Outcome Measures

Neurological morbidity and seizure control (as determined by themodified Engel classification40) were assessed in patients who hada minimum of 6 months of follow-up after undergoing surgery.Neurological evaluations were performed preoperatively, in the imme-diate postoperative period, and daily until discharge from hospital.

Additionally, neurological status was recorded at follow-up visits at 1, 6,12, and 24 months and at extended follow-up (defined as last follow-upbeyond the 24-month visit) postoperatively. Postoperative neurological

morbidity, determined as alteration of neurological function with respectto preoperative neurological evaluation, was classified as normal (nochange from baseline neurological function), SMA syndrome (contra-lateral hemiparesis/hemiplegia or apraxia with or without speechimpairment), or permanent neurological deficit (neurological impair-ment that was sustained after the 6-month evaluation and did not recoverby the last follow-up visit). Surgical complications, including infectionand intracranial hemorrhage, were recorded. For the purpose of analysis,pathological results were classified as forms of dysplasia, eg, focal corticaldysplasia, microdysgenesis, heterotopia, and cortical malformation; otherpathology, including gliosis, tumor, and inflammation; normal histo-pathological specimen.

Operative Approach

Thirty-five patients (89.7%) had subdural electrocorticographic mon-itoring with electrode grid and strip arrays, depth electrodes, ora combination thereof. The operative approach for each patient wasdetermined after neuroimaging studies, video-EEG, intraoperative andextraoperative mapping, and evaluation by the St. Louis ChildrensHospital and Cincinnati Childrens Hospital Medical Center multidis-ciplinary 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 frompatients were sent for pathological evaluation.

Statistical Methods

Dataare presented as mean6

SD for continuous variables and median(25th and 75th percentiles) for ordinal variables. For categoricalvariables, data are the number of patients (percent of group). Unlessotherwise noted, the Wilcoxon test was used for comparisons ofcontinuous variables, and the Fisher exact test was used for comparisonof categorical variables. For correlation studies, the Spearman correlation

was used to analyze data. A value ofP# .05 was considered statisticallysignificant. A denominator is included when less than the completepatient cohort provided data for the categorical variables. The dataanalysis was generated with SAS software version 9.2 of the SAS Systemfor Linux (SAS Institute Inc, Cary, North Carolina).

TABLE 1.Demographics and Seizure Characteristics in Patients

Who Underwent Surgical Treatment in Medial Frontal Lobe for

Medically Intractable Seizuresa

Total patients, n 39Female sex, n (%) 19 (49)Right handedness, n (%)b 24 (71)Age at seizure onset, mo 62.1 6 50Age at surgery, mo 146 6 57Time between seizure onset and surgery, moc 82.5 6 60Seizure type, n (%)

CPS 14 (36)CPS-secondary generalized 4 (10)SPS 7 (18)

SPS-secondary generalized 4 (10)Multiple seizures/generalized 10 (26)Seizure types (25th, 75th percenti les), n 2 (1, 2)

Preoperative seizure frequency, n (%)c

Monthly 4 (11)Weekly 6 (16)Daily 28 (74)

aCPS, complex partial seizures; SPS, simple partial seizures.bData from 34 of 39 patients.cData from 38 of 39 patients.

POSTOPERATIVE PEDIATRIC SMA SYNDROME

NEUROSURGERY VOLUME 70 | NUMBER 5 | MAY 2012 | 1153



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RESULTS

Patient and Seizure CharacteristicsThirty-nine patients underwent surgery in the region of the

medial frontal lobe for medically intractable epilepsy at St. LouisChildrens Hospital and Cincinnati Childrens Hospital MedicalCenter from 1994 to 2010 (Table 3). Of the 39 patients includedin 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 62.16 50 months, and age at thetime of surgery was 146 657 months. Surgery was performed82.56 60 months after identification of epilepsy. With regard toseizure characteristics in the study cohort, 14 (36%) had complexpartial seizures, 4 (10%) had complex partial seizures withsecondary generalized tonic-clonic seizures, 7 (18%) had simple

partial seizures, and 4 (10%) had SPS with secondary general-ization. Multiple seizure types were found in 10 patients (26%).The median number of seizure types in the patient populationwas 2. Seizures were experienced daily in 28 patients (74%),weekly in 6 patients (16%), and monthly in 4 patients (11%). Allpatients failed AED therapy with at least 2 drugs at therapeuticdoses. Patient demographics and seizure characteristics aresummarized in Table 1. Table 3 lists individual patient infor-mation, including demographics, clinical profile, pathology, andneurological impairment after surgery.

Neurophysiologic Monitoring and Surgical Resection

Thirty-five patients (90%) underwent invasive subdural mon-itoringbefore surgical resection. Lesionectomy was performed in 8patients (21%). Tailored resections were performed in theremaining 31 patients (79%), with 5 patients (13%) undergoingmultiple subpial transections in addition to tailored resections. Inall cases, intraoperative cortical stimulation mapping and somato-sensory evoked potentials were used to localize the eloquentprimary motor cortex and central sulcus. In cases when intra-operative cortical stimulation mapping and/or somatosensoryevoked potentials were unreliable (particularly in the younger

patients), extraoperative mapping data acquired from subduralgrid electrode placement were used for planning the resections.

Cortical and subcortical stimulation mapping was generallyrepeated after the resections to confirm the integrity of thecorticospinal tracts using techniques previously described.41-43

The location and extent of surgical resection are summarized inTable 2. The median distance of the posterior border of resectionanterior to the precentral sulcus was 0.50 cm. The mediandistance of the inferior border of resection superior to thecingulate gyrus was 0.6 cm. The median distance lateral to thelongitudinal fissure was 0.05 cm. The anteroposterior extent ofresection was 3.95 cm; the superior-inferior extent of resectionwas 2.9 cm; and the transverse extent of the resection was 3.0 cm.Preoperative MRI identified lesional cases in 16 patients (41%)and nonlesional cases in 23 patients (59%).

Neurological Outcome

After surgical resection in the medial frontal lobe, 17 patients(44%) developed SMA syndrome. No neurological impairmentwas found after surgery in 16 patients (41%). Six patients (15%)developed neurological impairment that did not resolve at the lastfollow-up. The development of postoperative SMA syndrome wasnot related to age at seizure onset, age at time of surgery, sex,handedness, preoperative seizure type, pathology of seizure focus,use of invasive monitoring, or surgery type. The delay betweenonset of seizures andsurgery wasfound to be significantly longer inpatients who developed SMA syndrome (P= .03). Preoperative

MRI did not identify a lesion in 23 patients (59%). The majorityof patients who developed SMA syndrome (82%) had no lesionidentified on preoperative MRI. Three patients (18%) withpostoperative SMA syndrome and 3 patients (50%) withpermanent impairment had lesions identified on preoperativeMRI. In patients with no neurological impairment, a significantlylarger number of patients (10, 62%) were found to have a lesionaldiagnosis on preoperative MRI (P= .05).

Of the 17 patients who developed SMA syndrome, 7 hadresolution of symptoms by 1 week postoperatively, another 7 had

TABLE 2. Extent and Location of Surgical Resection and Association Between Neurological Deficit and Resection Parametersa

Variable

Entire

Group

Neurological Deficit (25th, 75th Percentiles), cm

P

No Impairment

(n = 12)

SMA Syndrome

(n = 16)

Permanent Impairment

(n = 6)

Distance anterior to precentral sulcus, cm 0.50 (0, 1.62) 2.22 (1.00, 3.26) 0.20 (0.00, 1.45)b

0.00 (0.00, 0.00)b

.001Distance superior to cingulate gyrus, cm 0.60 (0, 1.00) 1.00 (0.30, 1.24) 0.52 (0.00, 0.85) 0.00 (0.00, 0.75)b .05Distance lateral to fissure, cm 0.05 (0, 3.29) 0.40 (0.00, 2.52) 0.50 (0.00, 3.47) 0.05 (0.00, 0.30) .67Anteroposterior extent of resection, cm 3.95 (3.07, 5.70) 3.51 (2.25, 4.05) 4.13 (3.34, 5.73) 5.28 (3.10, 6.75) .08Superior-inferior extent of resection, cm 2.90 (2.10, 4.80) 4.12 (2.30, 5.92) 3.15 (2.04, 4.55) 2.55 (2.25, 3.00) .35Transverse extent of resection, cm 3.00 (1.90, 3.70) 3.03 (2.15, 4.35) 2.98 (1.80, 3.70) 2.90 (1.90, 3.00) .57

aSMA, supplementary motor area.Pvalue 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.bP, .05 vs no impairment by Tukey-adjusted least-squares means.

KASASBEH ET AL




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resolution of symptoms between 1 week and 1 month post-operatively, and 3 had their SMA syndrome resolve beyond 1month after surgery. The resolution of SMA syndrome was notstatistically associated with the age at seizure onset, age at time ofsurgery, 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 syndromeafter surgery for placement of subdural grid and strip electrodes,not after surgical resection. This patient developed contralateralhemiplegia and mild expressive aphasia shortly after surgery.Motor and speech impairment gradually improved with completeresolution by 1 week postoperatively.

Seizure Outcome

Seizure outcomes as determined by Engel classification40 at12 months and extended follow-up visits are summarized inTables 5 and 6. At 12 month postoperatively, 31 of 37 patients(84%) had Engel class I or II, and 6 patients (16%) had Engelclass III or IV. Seizure outcome at 12 months postoperatively wasnot found to be significantly associated with age at seizureidentification, age at time of surgery, delay between seizureidentification and surgery, sex, handedness, seizure type, use ofinvasive 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 tohave Engel class I/II, whereas no patient with Engel class III/IVhad undergone lesionectomy. A Fisher exact test did notdemonstrate a statistically significant relationship between seizureoutcome and type of surgery performed (P= .31).

At extended follow-up, 16 of 22 patients (73%) had Engel classI/II, whereas 6 patients (27%) had Engel class III/IV. Age at thetimeofsurgerywas1736 38 months for patients with Engel classI/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 andsurgery was significantly longer (P= .05) in patients with Engelclass I/II (108 6 67 months) compared with patients with Engelclass III/IV (45.0 6 25 months). With regard to surgery type,lesionectomy was performed in 4 patients (25%) found to haveEngel class I/II, whereas 1 patient (17%) with Engel class III/IVhad lesionectomy performed. Seizure outcome at the last follow-up was not significantly associated with age at seizure identifi-

cation, sex, handedness, seizure type, use of invasive monitoring,preoperative MRI identification of lesion, surgery type, orpathological diagnosis.

Changes in seizure outcome between 1 month and eachsubsequent visit were analyzed. The majority of patients main-tained the same outcome at 1 month with no decline in Engel classthroughout the follow-up period; 87% at 6 months, 81% at 12months, 70% at 24 months, and 64% at the last follow-upmaintained the same seizure outcome as at 1-month. Theproportion of patients who had a decline in seizure outcome

TABLE3.Continued

Patient

AgeatSurgery,

mo

Se

xHandedness

SeizureType

Sideof

Surgery

Pathology

ImmediatePostop

erative

NeurologicalImpa

irment

29

197

M

R

Multipleseizures/generalize

d

R

Microdysgenesis

Contralaterallowerlimbweak

ness

30

158

F

L


d

L

Corticaldysplasia

Contralateralhemiparesis,aph

asia

31

32

F

R

CPS

R

Corticaldysplasia

Noneurologicalimpairment

32

169

F

R

CPS

L

Corticaldysplasia


asia

33

171

M

R

CPS-secondarygeneralized

L

Corticaldysplasia


asia

34

181

F

R

CPS

L

Corticaldysplasia


35

162

M

R


L

Corticaldysplasia

Contralateralhemiparesis,con

tralateralfacial

weakness,aphasia

36

197

F

R

CPS

L

Corticaldysplasia


asia

37

142

M

L


d

L

Corticaldysplasia

Contralateralupper-limbweak

ness,

facial

weakness

38

132

M

R


L

Corticaldysplasia


39

123

F

R


d

L

Corticaldysplasia

Contralateralhemiparesis,

facialweakness,

aphasia

aAVM,arteriovenousmalformation;

CPS,complexpartialseizures;SPS,simplepartial

seizures.

KASASBEH ET AL




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compared with 1 month was 13% at 6 months,16% at 12months,23% at 24 months, and 32% at the extended follow-up. Analysisof patient and seizure characteristics and their relation to pro-gression of seizure outcome throughout the follow-up period wasperformed. Statistically significant changes were not foundbetween change in seizure outcome and age at seizure onset, age

at time of surgery, time delay between seizure identification andsurgery, sex, use of invasive monitoring, surgery type, or seizuretype. Interestingly, right-handedness was associated with preser-vation of Engel class throughout the follow-up period, whichwas statistically significant (P = .02 at 12 months, P = .03 at24 months).

The association between early postoperative seizure recurrenceand seizure outcome at subsequent follow-up visits was studied(Table 7). Seizure recurrence in the first month postoperativelywas associated with a significantly increased likelihood of seizuresat the 6- and 12-month follow-up visits (P, .001 for both), anda nonsignificant trend toward seizure recurrence at extendedfollow-up visit (P= .12). Furthermore, seizure freedom duringthe first month postoperatively was significantly related tofavorable seizure outcome at the 6-month postoperative visit(P = .009). In contrast to long-term seizure outcome, earlypostoperative seizure recurrence was not associated with post-operative neurological outcome.

Association of Extent and Location of Resection With

Clinical Characteristics

Analysis of the relation between the extent and location ofresection with patient characteristics and progression of seizureoutcome is shown in Table 8. The dimensions of the surgicalresection and the location of resection did not correlate

significantly with age at seizure identification, age at the timeof surgery, or time delay between seizure identification and timeof surgery (Table 8). Anteroposterior extent of surgical resectionwas found to be associated significantly with sex (P= .04), withmale patients undergoing more extensive anteroposterior resec-tions (male patients, 4.40 cm; female patients, 3.14 cm). Otherresection parameters were not associated with sex. Furthermore,none of the surgical parameters was found to be associated withhandedness. Interestingly, a significantly more extensive resectionlateral to a longitudinal fissure was associated with pathologies

TABLE4.NeurologicalImpa

irmentAfterSurgeryintheMedialFrontalLobeandResolutionofSupplementaryMotorAreaSyndromea

Variable

NeurologicalDe

ficit

P

SMASyndrome(n=

17)

NoImpairment

(n=16)

Resolvedby

1wk(n=7)

ResolvedBetween

1wkand1mo(n=

7)

ResolvedAfter

1mo(n=3)

Permanent

Impairmen

t(n=6)

Ageofseizureonset,mo

57.6

6

58

76.3

6

46

46.3

6

33

27.0

6

39

89.0

6

48

.31

Ageatsurgery,mo

1266

68

1696

17

1486

65

1776

27

1526

44

.60

Timebetweenseizureonsetandsurgery,mo

62.7

6

60

92.1

6

45

1036

68

1506

64

63.3

6

46

.07

Femalesex,n(%)

9(56)

2(29)

4(57)

1(33)

3(5

0)

.78

Righthandedness,n/N(%)

9/14(64)

5(71)

5/6(83)

3(100)

2/4(5

0)

.72

Seizuretype,secondarygene

ralized,n(%)

5(31)

2(29)

0

0

1(1

7)

.52

Invasivemonitoring,n(%)

14(88)

6(86)

7(100)

3(100)

5(8

3)

.93

PreoperativeMRI,lesional,n(%)

10(62)

2(29)

0

1(33)

3(5

0)

.05

Surgerytype,

lesionectomy,n

(%)

5(31)

1(14)

0

0

2(3

3)

.42

Pathology,

formsofdysplasia

,n/N

(%)

10/15(67)

6(86)

6(86)

0

3(5

0)

.08

aSMA,supplementarymotorarea.

TABLE 5.Seizure Outcome After Surgery in the Medial Frontal

Lobe

Patients, n (% of Group)

Engel Class

At 12 mo

(n = 37)

At Extended

Follow-up (n = 22)

I 25 (68) 12 (55)II 6 (16) 4 (18)III 4 (11) 5 (23)IV 2 (5) 1 (5)





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categorized as dysplasia. Resection parameters were not associated

with seizure outcome at the 12-month and extended follow-upvisits, with the exception of that a significantly smaller transverseresection was associated with favorable seizure outcome at the12-month follow-up (P= .05).

Neurological deficit after surgical resection was found to bestrongly associated with the distance of resection margin from theprecentral sulcus (P, .001; Table 2). Postoperative neurologicaldeficit had a nonsignificant trend association with the ante-roposterior extent of surgical resection (P = .08). Moreover,a significant association was found between distance of theresection margin superior to the cingulate sulcus and thedevelopment of neurological deficit (P = .05). No significant

association was found between the development of postoperativeneurological deficit and the surgical resection extension lateral tothe longitudinal fissure, the superior-inferior extent of resection,or the transverse extent of resection.

Permanent Neurological Deficit

Six patients (15%) in this series undergoing medial frontal loberesections had permanent deficits that persisted for. 6 monthsafter surgery (Table 3). They were divided evenly between boysand girls. Four had left-sided surgery, and 2 had right-sidedsurgery. Preoperative MRI identified lesional cases in 3 patients.Three had cortical dysplasia, 2 had nonspecific changes such asgliosis, and 1 had no histopathological abnormality. Most of thedeficits (contralateral hemiparesis) had significantly improved buthad not entirely resolved at 6 months and persisted through thefollow-up period. Table 2 summarizes the extent and location ofsurgical resection in patients who developed permanent neuro-logical deficit. In no patient was the primary motor cortex

knowingly resected. Distances of resection from precentral sulcusand cingulate gyrus were significantly shorter in patients whodeveloped permanent impairment. Furthermore, there wasa trend toward larger anteroposterior dimension of resection in

TABLE 6.Association Between Engel Class and Patient Characteristicsa

Variable

Engel Class at 12 mo Engel Class at Extended Follow-up

I/II (n = 31) III/IV (n = 6) P I/II (n = 16) III/IV (n = 6) P

Age of seizure onset, mo 61.7 6 52 48.0 6 36 .78 65.3 6 53 53.5 6 63 .44

Age at surgery, mo 149 6 60 128 6 43 .18 173 6 38 98.9 6 64 .02Time between seizure onset and surgery, mo 85.5 6 64 79.8 6 50 .95 108 6 67 45.0 6 25 .05Female sex, n (%) 17 (55) 2 (33) .40 6 (38) 4 (67) .35Right handedness, n (%) 21/27 (78) 3 (50) .31 10/13 (77) 4 (67) 1.0Seizure type, secondary generalized, CPS or SPS, n (%) 6 (19) 1 (17) 1.0 2 (12) 0 1.0Invasive monitoring, n (%) 27 (87) 6 (100) 1.0 14 (88) 6 (100) 1.0Preoperative MRI, lesional, n (%) 14 (45) 2 (33) .68 7 (44) 3 (50) 1.0Surgery type, lesionectomy, n (%) 8 (26) 0 .31 4 (25) 1 (17) 1.0Pathology, forms of dysplasia, n (%) 22 (71) 3 (50) .37 10 (62) 1 (17) .15

aCPS, 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 (%)

PFollow-up Seizure Outcome Early Postoperative Occurrence Seizure Freedom

6 mo Seizure recurrence 9 (100) 6 (20) ,.001Seizure freedom 0 24 (80)

Engel III/IV 5 (56) 3 (10) .009Engel I/II 4 (44) 27 (90)

12 mo Seizure recurrence 8 (100) 10 (34) .001Seizure freedom 0 19 (66)Engel III/IV 3 (38) 3 (10) .10Engel I/II 5 (62) 26 (90)

Extended follow-up Seizure recurrence 4 (100) 9 (50) .12Seizure freedom 0 9 (50)Engel III/IV 1 (25) 5 (28) 1.0Engel I/II 3 (75) 13 (72)

KASASBEH ET AL




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patients who developed permanent impairment, although thisdid not achieve statistical significance (Table 2).

ILLUSTRATIVE CASES

Case 1Patient 1 is a 4-year-old boy with an unremarkable medical

history who presented to medical attention with seizure activity.He was evaluated by a neurologist, who treated him withcarbamazepine, levetiracetam, valproate, phenytoin, and zonisa-mide both alone and in combination. None of these medicationsprovided adequate seizure control, and the patient continued tohave daily unrelenting seizures despite medical therapy.

His seizures initially involved extension of his right upperextremity but subsequently evolved into stereotypic movements

and posturing involving his bilateral upper and lower extremities.He was evaluated by the multidisciplinary epilepsy team. Hisseizure focus was thought to involve the left mesial frontallobe. Video-EEG suggested a left-sided seizure focus. A positronemission tomography scan showed a region of hypometabolism

in the left mesial frontal lobe, and an MRI showed a corticalabnormality consistent with focal cortical dysplasia in this region.Invasive monitoring was recommended to the patient and familyto better define the ictal onset and eloquent cortex.

A left-sided frontoparietal craniotomy was performed withplacement of subdural grids and strips overlying the lateral leftfrontal, lateral left parietal, mesial left frontal, and mesial leftparietal lobes. Mapping was performedfor anatomic localizationoftheprimary motor cortex. After the initial craniotomy forgrids andstrips placement, the patient had seizure activity allowing mapping

TABLE 8. Association Between Extent and Location of Resection With Patient Characteristics and Seizure Outcome a

Variable

Extent and Location of Resection

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

Age of seizure onset (n = 34)r 20.23 20.12 20.01 0.09 20.30 20.18P .19 .48 .95 .62 .09 .32

Age at surgery (n = 34)r 20.12 0.10 .20.03 0.04 20.04 20.24P .50 .56 .88 .83 .80 .17

Time between seizure onset andsurgery (n = 34)r 0.04 0.06 0.12 0.11 0.21 20.10P .82 .72 .50 .52 .24 .56

SexFemale (n = 16) 0.94 (0, 2.70) 0.43 (0, 0.95) 0.05 (0, 3.29) 3.14 (2.70, 4.03) 3.00 (2.09, 5.40) 3.27 (2.05, 4.00)Male (n = 18) 0.25 (0, 1.00) 0.75 (0, 1.00) 0.15 (0, 1.80) 4.40 (3.75, 6.70) 2.90 (2.25, 3.80) 2.73 (1.90, 3.26)P .17 .47 1.00 .04 .50 .27

HandednessLeft (n = 8) 1.00 (0.25, 1.59) 0.36 (0, 0.95) 0.68 (0, 2.52) 4.13 (3.43, 6.40) 2.88 (2.00, 4.30) 3.45 (2.88, 3.95)Right (n = 21) 0.40 (0, 1.83) 0.76 (0, 1.10) 0.30 (0, 3.41) 3.80 (3.07, 5.60) 3.00 (2.08, 4.80) 3.00 (1.90, 3.80)P .67 .52 .92 .42 .63 .48

PathologyForms of dysplasia (n = 22) 0.90 (0, 1.83) 0.60 (0, 1.00) 1.03 (0, 3.52) 3.85 (3.07, 5.70) 3.25 (2.41, 4.80) 3.26 (2.10, 3.80)Other (n = 11) 0 (0, 1.00) 0 (0, 1.00) 0 (0, 0.80) 4.00 (3.50, 6.75) 2.75 (2.00, 5.10) 2.10 (1.60, 3.00)P .07 .34 .04 .69 .80 .09

Engel class, 12- mo follow-upI/II (n = 27) 0.50 (0, 2.10) 0.60 (0, 1.00) 0.00 (0, 3.29) 4.00 (3.07, 5.60) 3.25 (2.10, 4.80) 2.70 (1.90, 3.29)III/IV (n = 5) 0.50 ()0, 1.00) 0.59 (0.45, 0.75) 0.10 (0, 3.52) 3.50 (3.10, 6.75) 2.50 (2.50, 4.80) 3.70 (3.60, 4.43)P .63 .98 .54 .82 .96 .05

Engel class, extended follow-up

I/II (n = 13) 0.00 (0, 1.00) 0.00 (0, 0.80) 0.00 (0, 0) 4.00 (3.75, 5.30) 3.50 (2.75, 4.80) 2.10 (1.70, 2.80)III/IV (n = 5) 1.00 (0, 2.80) 0.00 (0, 1.00) 0.00 (0, 0) 3.50 (2.50, 4.00) 3.25 (2.50, 5.50) 4.50 (2.00, 4.80)P .43 .96 1.0 .32 .96 .15

aFor continuous characteristics, data are Spearman correlation (r) with associatedP value. For categorical characteristics, data are median (25th, 75th percentile) for the

distances wherePvalues compare the distances across characteristic subgroups by the Wilcoxon test. Values in parentheses are 25th and 75th percentiles when appropriate.





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of his seizure focus to the left SMA. A second craniotomy forseizure focus resection on postoperative day 2 was performed(Figure 1). Permanent pathology revealed cortical dysplasia.

After the resection of the seizure focus, the patient had right-sided weakness and was abulic. He received steroids and wasobserved in the pediatric intensive care unit. He gradually regained

his ability to ambulate before discharge. At his first outpatientfollow-up, he was noted to be seizure free with complete resolutionof his hemiparesis.

Case 2

Patient 2 is a 12-year-old boy who initially presented to theepilepsy clinic with seizures beginning at 6 years of age. Theseseizures showed stereotypic clonic activity in his left upper andlower extremities initially but subsequently began involving morecomplex movements and posturing. With rare exception, hisseizures occurred at night. He had been on oxcarbazepine,levetiracetam, topiramate, and valproic acid without adequateseizure control.

Patient 2 was evaluated with multiple imaging studies, whichincluded normal MRIand positron emission tomography showingbilateral temporal hypometabolism. Video-EEG showed evidence

of right frontal seizure focus. After evaluation of all of thediagnostic studies, invasive monitoring with cortical andinterhemispheric grids and strips was recommended to the patientand family.

A right-sided frontoparietal craniotomy was performed withplacement of subdural grids and strips overlying the lateral right

frontal and right parietal lobes (Figure 2). A dual-layered arraywas placed overlying the mesial right frontal and parietal lobes.After several days of monitoring, 7 typical seizures were captured,but the seizure focus was not confidently localized on theavailable invasive arrays. Thus, on postoperative day 5, thepatient had additional right parietal and new left frontal subduralstrip electrodes placed to try to exclude a more remote ictal onset.During these 2 surgeries, the primary motor cortex was mappedfor planning of his resection. After additional monitoring, theseizure focus was ultimately localized to the right SMA, andhe was taken to the operating room for resection. Permanentpathology revealed subpial astrocytosis and an increase in neuronsin the white matter of the lesion.

Postoperatively, the patient suffered from a left-sided hemi-paresis and facial weakness. His motor function quickly improved,although he remained with a small amount of left lower-extremity

FIGURE 1. In each intraoperative photo, note that the operative field is oriented as indicated in A. A, intraoperative picturedemonstrating 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 skullradiograph demonstrating placement of subdural grids and strips.

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weakness 1 month postoperatively. He was last seen in clinic3.5 years postoperatively without any further seizure activity butmildly diminished left foot coordination.

DISCUSSION

SMA Anatomy and Function

First described by Penfield and colleagues,44-47 the SMAcomprises a distinct anatomic and functional region of thecerebral cortex situated largely on the mesial aspect of the superiorfrontal gyrus.46 The SMA is limited posteriorly by the precentral

sulcus and inferiorly by the cingulate sulcus and genu of corpuscallosum.46-49 The anterior and lateral borders are less definite.Early cortical stimulation studies indicated that the SMA extendsup to 5 cm anterior to the precentral sulcus and laterally to thesuperior frontal sulcus.49 More recent studies suggest thatthe 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 primarymotor cortex and to spinal cord, and a rostral pre-SMA or F6,which receives projections from the prefrontal cortex and

cingulate motor areas.51 The SMA is principally motor infunction and has reciprocal connections with multiple compo-nents of the motor system, including the premotor cortex, primarymotor cortex, cingulate gyri, basal ganglia, and spinal cord (withdirect contributions to the descending corticospinal tracts),in addition to connections to the contralateral SMA.50,52-57

Although predominantly motor, the SMA also serves a sensoryrole46,50 and receives input from sensory cortex and parietalsensory association areas.53,58 Furthermore, electric stimulation ofthe SMA has been demonstrated to result in autonomic responses,vocalization, inhibition of voluntary activity (most often speech),

assumption of characteristic postures, and changes in sensoryperception.46,59-62 These features may also be evident duringseizures arising from the SMA.59

Stimulation studies have demonstrated a somatotopic organi-zation of the human SMA,50 contrary to its initial description.46

These studies revealed the lower limb, upper limb, and headrepresentations to extend from the posterior to anteriormargins.50 Sensory representation may be either anterior orposterior to the motor representation.50 Fontaine et al31 showeda correlation between immediate postoperative deficits and the

FIGURE 2. In each intraoperative photo, note that the operative field is oriented as indicated in A.A, intraoperative picturedemonstrating placement of right frontal and parietal cortical array. B, intraoperative picture demonstrating motor cortexrepresenting hand control (H). C, intraoperative image demonstrating resection of the right frontal seizure focus in the sup-plementary motor cortex.D, plain skull radiograph demonstrating placement of subdural grids and strips in the patients indexoperation.





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anteroposterior extent of SMA resection. Postoperative aphasiaalone developed with resection of the most anterior part of the leftSMA, aphasia with motor impairment in the face and upper limbwith resection extending more posteriorly, and contralateralhemiparesis and aphasia when the complete left SMA wasresected. Other studies of SMA syndrome after surgical resection

of the medial frontal lobe also indicate increased incidence andseverity of SMA syndrome with increased anteroposterior extentof resection in the mesial frontal lobe.32,38,39 Such somatotopy ispertinent because it aids in predicting the extent of postoperativeneurological deficit.

The function of the SMA has been elucidated through variousmethods, including cortical stimulation,50,61 electrophysiologicalsingle-cell63,64 and field potential recordings,65 regional cerebralblood flow measurement,66,67 and functional MRI and positronemission tomography studies.35,68-71 The SMA is considereda supramotor region72 with a critical role in multiple aspects ofmotor control, including the programming, initiation, andexecution of complex motor sequences.46,49,50,63,72-82 Studieshave demonstrated an increase in regional cerebral blood flow inthe primary motor cortex and SMA during execution ofmovement.76,83 Even without execution of movement, anincrease in regional cerebral blood flow was shown in theSMA while programming a sequence of movements. The SMAcontrols proximal extremity muscle movement through directconnections to the spinal cord. It influences distal extremitymovement indirectly through the primary motor area.84

SMA Syndrome After Surgery

In 1977, Laplane et al33 studied 3 patients who underwent

resection of the medial frontal lobe for intractable epilepsy. Aftersurgery, a syndrome emerged over 3 stages. First (first and secondweeks), patients developed nearly complete akinesia (morepronounced contralaterally) associated with variable degrees ofspeech arrest. This was followed by a stage of rapid recovery ofmotor function of variable duration, although spontaneousmovement remained severely reduced contralaterally, with lim-ited spontaneous speech. Movements in contralateral limbs couldbe performed only after repeated spoken commands, and theirstrength was almost normal when performed. Third, after grossrecovery of motor function, there was residual motor impairmentin the form of impairment of alternating movements of thehands. This clinical syndrome was attributed to the resection of

the SMA. The observations of Laplane et al have been confirmedby other studies of resection of the SMA (Table 9).28-39

In this series, SMA syndrome was characterized primarily bypostoperative contralateral hemiparesis/hemiplegia. Most often,this was observed hours after surgery and improved gradually overthe next few days, with restoration of motor strength within 1 dayto 1 week of surgery in 41% of cases. The vast majority of cases(82%) resolved by the first outpatient visit at 1 month. Twopatients (5.1%) experienced impairment in fine motor ability thatwas sustained for a period of weeks to months after restoration of

motor strength. Speech impairment was noted in 9 patients(23.1%), typically expressive aphasia and hesitancy of speech. Ofpatients with speech impairment, 8 had surgery on the lefthemisphere and 1 had surgery on the right hemisphere. Speechimpairment usually resolved within days of surgery and resolved inall but 1 patient by the day of discharge. In 1 patient, speech

impairment continued to improve after discharge from thehospital and was reported to continue to improve at the firstpostoperative visit. The degree of speech impairment was oftendifficult to assess, however, because of the variability in pre-operative speech development in this cohort.

The incidence of SMA syndrome after resections of the SMA inadults is generally high (50%-100%; Table 9).28-39 A study byRussell and Kelly37 demonstrated an incidence of SMA syndromeof only 26% (n = 27) after resection of glial neoplasms involvingthe SMA. They attributed the higher incidence in previous seriescompared with their own to resection of functional cortex notinfiltrated by tumor. Resection of functional cortex was avoidedin their study by the use of stereotaxis to determine the posteriormargin of the mass. Additionally, Russell and Kelly reported thatno additional cortex was resected for purposes of epilepsy controlin their series. Differences in underlying pathology, surgicalprocedure applied, methods of determining the SMA region, andextent of SMA resection render comparing results of these studiesproblematic. In our study, 44% of patients developed SMAsyndrome, comparable to previous reports. Furthermore, 15% ofpatients in our study developed permanent neurological deficitafter surgery.

Minimizing the Risk of Permanent Deficit

Cortical resections in eloquent areas such as the SMA region androlandic cortex are fraught with risk of permanent neurologicaldeficits, particularly of contralateral motor function but alsolanguage and cognitive function. However, reluctance to imparta deficit should notexcessivelyobscure the goal of achievingseizurefreedom in these medically refractory patients. We have not yetseen a patient rendered seizure free but with postoperative motordeficit who would trade their freedom from seizures for recovery ofmotor function. Nevertheless, every effort is made to localize andpreserve eloquent cortex not involved in the ictal onset.85 Duringresections in this region, we find the combination of corticalstimulation mapping and intraoperative somatosensory evokedpotentials to be nearly universally successful in localizing the

primary motor cortex. Functional MRI and extraoperativecortical stimulation mapping are also used heavily in grid-based2-stage resections (35 of our 39 patients). Once the primarymotor cortex and ictal onset/early spread zones are identified,a tailored resection or lesionectomy is performed. During andafter resection, cortical stimulation mapping is repeated. In mostcases, a good cortical motor response can be elicited after theresection, with a similar threshold. When this is observed, thusconfirming the integrity of the corticospinal tract, the surgeonand family can be largely reassured that a postoperative motor

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TABLE 9. Previous Reports of Supplementary Motor Area Syndrome After Surgical Resection of Mesial Frontal Lobe a

Study (Year)

Patients

(Pediatric

Patients

and (age), n

Patient

Presentation

Underlying

Pathology (n)

Developed

SMA

Syndrome, %

Developed Other

Neurological

Complications, %

Duratio

From S

Laplane et al33

(1977)3 (0) Seizures N/A (patients underwent

surgery for intractableepilepsy)

100 N/A Patient 1:impairmmo; pa

to normfollow-normalup

Rostomilyet al36

(1991)

6 (0) Seizures, hemiparesis,speech impairment

Low-grade astrocytoma(4), anaplasticastrocytoma (1),metastatic breastadenocarcinoma (1)

100 N/A Motor funto nearto 8 wkrestrictspontaresolvemore wpostoppatientbaselin

Bleasel et al29

(1996)

10 (2; ages

13, 14)

Seizures Cortical dysplasia (2),

subpial gliosis (1),astrocytoma (2),ganglioglioma (1),astroblastoma (1),abscess (1), noabnormality (2)

60 N/A Patients r

baselin

Zentneret al39

(1996)

28 (0) Seizures (in 12 patients,surgery was indicatedfor medicallyintractable epilepsy),hemiparesis, aphasia

High and low-gradetumors (19),nontumorouslesions (9)

89 0 3-42 d (Mimpairmmotor fobservadditio

Bannur andRajshekhar28

(2000)

6 (0) Seizures Astrocytoma (grades Iand II)

100 0 2 Patientsbaselinpostopterm fopatientpatientshowedbaselin(with slalterna

Duffau et al30

(2001)1 (0) Seizures Low-grade glioma 100 0 Patient re

baselin

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TABLE 9. Continued

Study (Year)

Patients

(Pediatric

Patients

and (age), n

Patient

Presentation

Underlying

Pathology (n)

Developed

SMA

Syndrome, %

Developed Other

Neurological

Complications, %

Duratio

From S

Krainik et al32

(2001)23 (0) Seizures Low-grade glioma (17),

anaplasticastrocytoma (5),

cortical dysplasia (1)

65 N/A Recoveryd-6 wk comple

to monFontaine et al31

(2002)11 (0) Seizures, headache Low-grade astrocytoma

(7), anaplasticastrocytoma (1),anaplasticoligodendroglioma(2), glioblastoma (1)

100 N/A Recoverybetweed postoduratiod-3 moinitiatinmovemfor prodespitemotor s

Peraud et al34

(2002)24 (0) Seizures, speech

disturbances, motorimpairment,headache, memory

deficits

Astrocytomas (grade II) 83 8 Recoverypostop12 mo,patient

followedeficitsimpairmrespect

Russell andKelly37 (2003)

27 (0) Seizures, hemiparesis,headache

High- and low-gradetumors

26 8 4% Had Sat the 1postopexaminfrom 26

Ulu et al38

(2008)12 (3; ages

10, 11,and 14 y)

Seizures (4 patientsunderwent surgery formedically intractableepilepsy), hemiparesis

Low- and high-gradetumors (9),nontumorouslesions (3)

50 N/A 1 mo-1 y;motor i1 year i

Rosenberget al35 (2010)

26 (0) Seizures, motor andspeech impairment

High- and low-gradegliomas, metastaticlesions, cavernoma,cortical dysplasia,meningioma

23.1 N/A

aAED, antiepileptic drug; SMA, supplementary motor area.

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deficit is most likely SMA syndrome, and the prognosis for motorrecovery is excellent. Should the cortical stimulation threshold besignificantly increased or responses no longer obtained or ifresection involves the primary motor cortex, a permanent deficitis more likely the outcome. Nevertheless, substantial improve-ment is generally the rule (Table 3).

We have observed 2 predominant patterns of recovery in ourpatients. Those that ultimately go on to have SMA syndromewithout permanent deficit may have a profound hemiplegia withneglect in the first hours or days after surgery and recovery ofmovement in distal extremities (finger and toe fine movements)first. Patients with permanent deficits regain proximal movementfirst, consistent with pyramidal/corticospinal tract injury. Thus,a patient with an intact cortical stimulation threshold at thecompletion of resection who recovers some finger movement inthe first week most likely has pure SMA syndrome with anexcellent prognosis for recovery. Our 6 patients with residualpermanent deficits demonstrated little improvement beforedischarge from the hospital. In those who showed some recoverybefore discharge, improvement in proximal movement wasoften noted.

Berger et al86 reported that resections within 1 cm of eloquentcortex have a substantially increased risk of irreversible deficit. Wehave found that resections in the SMA region, within 1 cm of theprecentral gyrus, also have the highest rate of postoperative deficit(Table 2). However, careful preservation of the precentral gyruswith a subpial aspiration technique back to the precentral sulcuscan result in excellent outcomes with no deficit once the SMAsyndrome resolves. Care should be taken not to undercut thewhite matter of the precentral gyrus, and frequent subcorticalmapping during the resection can help ensure the integrity of the

descending tracts of the primary motor areas. For patients whodeveloped permanent neurological deficit in our series, distancesof resection from precentral sulcus and cingulate gyrus weresignificantly shorter compared with those in patients with noneurological impairment. Moreover, there was a trend towardlarger anteroposterior dimension of resection in patients whodeveloped permanent impairment. In none of the patients whodeveloped permanent deficit was the primary motor cortexknowingly resected. Further studies investigating the develop-ment of permanent deficit after resection of the SMA proper vspre-SMA are warranted.

Neurological RecoveryThe transitory nature of neurological impairment is the

hallmark of SMA syndrome. Of the 17 patients in this studywho developed SMA syndrome, 7 (41%) had resolution ofsymptoms by 1 week postoperatively, 7 (41%) had resolution ofsymptoms between the 1-week and 1-month follow-up visits, and3 (18%) had resolution of symptoms after the 1-month follow-upvisit. The rate of resolution of SMA syndrome was not found tosignificantly correlate with patient characteristics, seizure charac-teristics, use of invasive monitoring, or surgery type. Interestingly,

the delay between seizure identification and surgical resection wasfound to be significantly longer in patients who developed SMAsyndrome. The significance of this finding is uncertain. Patientswith a preoperative MRI lesion were significantly less likely tosuffer neurological impairment after surgical resection. Themajority of patients who developed postoperative SMA syndrome

were not found to have a lesional diagnosis on preoperative MRI.This may suggest that in nonlesional cases, neuroplastic changesare more capable of compensating for anatomic resections in theregion of the SMA. Further studies are needed to validate thishypothesis. Furthermore, male patients were found to haveundergone significantly more extensive anteroposterior resections.A physiological-anatomical explanation for such a sex difference iselusive, suggesting that this statistical finding may be attributed totype II error.

The development of SMA syndrome strongly correlated withthe proximity of surgical resection to precentral sulcus. Moreover,the anteroposterior extent of surgical resection was also correlatedwith the development of SMA syndrome. This is consistent withprevious reports in adults in which patients more frequentlymanifested motor impairment with surgical resection extendingfurther into the caudal SMA.32,34,39 Furthermore, a significantcorrelation was found in our series between the development ofthe SMA syndrome and the distance of the inferior border ofresection to cingulate sulcus. This finding is consistent withprevious studies in adults.87,88 However, Russell and Kelly37 didnot find a correlation between violation of cingulate gyrus andincreased frequency of SMA in their series. Additionally,a significantly more extensive resection lateral to longitudinalfissure was associated with pathologies categorized as dysplasia.

The mechanism of resolution of SMA syndrome is not fully

understood, although recruitment of contralateral SMA and intactipsilateral premotor cortex after surgical resectionare believed to becritical in this recovery.35,89-91 Supporting this is the finding thatbilateral surgical resection of the SMA resulted in protractedmotor and speech impairment.92 One proposed hypothesis toexplain restoration of SMA function after surgery in the medialfrontal lobe for tumors is the displacement of functioning SMAby the tumor.28 Such displacement may partially explain thetransitory nature of SMA syndrome in patients with slow-growing tumors but does not satisfactorily account for the similarevolution of SMA syndrome in patients who undergo surgicalresections for other purposes and in whom other underlyingpathology is identified. Several lines of evidence converge on the

occurrence of plastic brain mechanisms reestablishing SMAfunction.30,93 Duffau et al30 studied the development of SMAsyndrome after resection of a low-grade glioma invading theSMA. The patient demonstrated no motor or speech disturbancesat the end of tumor removal. Nearly 30 minutes after theresection, aphasia and contralateral hemiplegia developed. ThisSMA syndrome continued for 10 days and was followed bygradual improvement, with total recovery observed at 2 monthsafter the resection. This progression may be explained by short-term plasticity predicated on unmasking of parallel networks in





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addition to the residual activity of an oscillatory loop, with long-term recovery attributed to long-term plasticity.30 In thedeveloping brain, plasticity is undoubtedly an important con-tributing factor in resolution of SMA syndrome in pediatricpatients.94-96 Future studies elucidating the precise underlyingmechanisms of resolution of SMA syndrome are needed to

validate these hypotheses.

Seizure Outcome

The majority of patients had favorable seizure outcome (Engelclass I or II) at the 12-month and extended follow-up visits (84%and 73%, respectively). Lesionectomy was performed in 26% ofpatients with Engel class I/II at the 12-month postoperativefollow-up, whereas none of the patients who had Engel class III/IVhad lesionectomy. Similarly, at the last follow-up, more patientswith Engel class I/II were found to have undergone lesionectomy.These findings notwithstanding, our analysis did not demonstratea statistically significant relationship between seizure outcome andtype of surgery performed. The absence of statistical significancecompared with patients who underwent other surgical proceduresmaybe explained by the fact that a large proportion of patients whodid not undergo lesionectomies also had favorable seizure out-come. In addition, the small number of patients who underwentlesionectomies may have precluded statistical significance. Ofnote, age at the time of surgery was significantly higher for patientswith Engel class I/II compared with patients with Engel classIII/IV at the extended follow-up. Furthermore, at the extendedfollow-up,the delay between seizureidentification andsurgery wassignificantly longer in patients with Engel class I/II compared withpatients with Engel class III/IV. These findings are not explainedby our data collection but may berelated to the underlying causeof

seizure disorder in younger vs older patients undergoing epilepsysurgery.Seizure outcome in the early postoperative period remained

largely unchanged throughout the follow-up period. Moreextensive anteroposterior extent of surgical resection was foundto be associated with an appreciable, albeit statistically insignifi-cant, decline in Engel class between the 1- and 6-month follow-upvisits. Similarly, a decline was found between the 1-month and12-month follow-up visits in the proximity of the posterior borderof the surgical resection to precentral sulcus. Additionally, a declinein Engel class was noted with more extensive superior-inferiorresections. Of note, the number of patients who experienceddeterioration in seizure outcome after the first month post-

operatively was small (n = 4-6). This may explain the absenceof statistical significance in our studies. Moreover, the variabilityin Engel class changes was not sufficient to allow further statisticalanalyses. In addition, early postoperative seizure recurrence wasassociated with a significantly increased likelihood of seizures atthe 6-month and 12-month follow-up visits and a nonsignificanttrend toward seizure recurrence at extended follow-up visit.These findings indicate that early seizure recurrence is a negativepredictor of seizure outcome. Long-term seizure control didnot correlate with dimensions of surgical resection, with the

exception that a significantly smaller transverse resection wasassociated with favorable seizure outcome at the 12-monthfollow-up, a finding of unclear significance. A decline in Engelclass over the follow-up period was significantly less probable inright-handed patients. This may be explained by patientsundergoing more conservative resections when surgery is

performed in the dominant hemisphere. Changes in Engel classwere not correlated with other patient characteristics, seizuretype, or surgery type.

CONCLUSION

Surgery in the region of the medial frontal cortex is associatedwith the development of SMA syndrome. In this study ofexclusively pediatric patients, fewer than half of the patientsdeveloped SMA syndrome. The SMA syndrome was characterizedprimarily by postoperative contralateral hemiparesis/hemiplegiathat developed within hours of surgery andresolvedin the majorityof cases by 1 month postoperatively. Development of post-

operative SMA syndrome was related to the anteroposterior extentof surgical resection and proximity of the resection to theprecentral and cingulate sulci. In addition, surgery in the medialfrontal lobe was associated with favorable seizure outcomes. Ourstudies show that resections in the SMA can be performed safelyin children and are associated with reversible neurologicalimpairment.

Disclosure

The authors have no personal financial or institutional interest in any of the

drugs, materials, or devices described in this article.

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COMMENT

The authors present an elaborate study on the occurrence and outcomeof supplementary motor area (SMA) syndrome and epilepsy outcome

among children with refractory epilepsy undergoing invasive monitoringand resections. This series is the largest to date describing the rate andoutcome of SMA syndrome in general and in children in particular.

Thirty-nine children with refractory epilepsy underwent resections oflesions (or nonlesional epileptic foci) located completely or partially in theSMA region. Twenty-three (60%) had postoperative neurologicalimpairment; 75% was transient and attributed to SMA syndrome. Theauthors found a significant correlation between the distance from theposterior resection margin and the precentral sulcus and the occurrence ofneurological impairment.

Seventeen of 23 children (74%) with no lesion had a new neurologicalimpairment as opposed to 6 of 10 children (37%) with lesions. Of thenonlesional cases, 14 (82%) were SMA syndrome comparedwith 3 (50%)ofthe lesionalcases.This may be explainedby theconceptthatresectionofnonlesional foci may be more extensive and thus cause more morbiditycompared with a lesionectomy (or even a lesionectomy plus whenadditional resection is tailored). However, in nonlesional cases, brainplasticity secondary to chronic seizures (often resulting from an ana-tomically ill-defined pathology such as cortical dysplasia or gliosis)compensates for the anatomic resection of the SMA compared withlesional cases in which brain plasticity has less occurred.

An additional point worth noting is the correlation between earlypostoperative seizure recurrence and long-term epilepsy outcome. Earlyseizure recurrence was associated with long-term seizures, and seizure

freedom during the first postoperative month was associated with long-term seizure freedom.

The authors are to be complimented on this interesting and importantstudy.

Jonathan Roth

Zvi Ram

Tel-Aviv, Israel

KASASBEH ET AL


characterization of the supplementary motor area syndrome and seizure outcome after medial frontal...

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