Electroclinical semiology of the bilateral asymmetric tonic seizures observed in patients with supplementary sensorimotor area epilepsy confirmed by pre- and post-operative MRI

Abstract

OBJECTIVE: To retrospectively reappraise characteristics of the electro-clinical seizure semiology of the bilateral asymmetric tonic seizure (BATS) in the patients with supplementary sensorimotor area (SSMA) epilepsy.

METHODS: From the retrospective analysis of the pre- and post-operative Magnetic Resonance Imaging (MRI) data involving 386 patients who received epilepsy surgery, 123 BATS were identified meeting the clinical criteria and included in the study. For comparison in four extremities involvement, limbs were paired and comparatively evaluated between the contralateral and ipsilateral sides, proximal and distal segments, and upper and lower limbs. For evaluation of sequential events, each tonic phase of the BATS was chronologically divided into 10 equal epochs. In each epoch, distribution of tonic events in 4 extremities and axes was visually evaluated and comparatively analyzed.

RESULTS: Asymmetric tonic posturing was the most constant findings in 6 patients, whose upper limbs contralateral to epileptogenic cortex were kept in abduction in all 123 (100%) seizures and extension in 118 (95.9%) seizures. This type of asymmetry became visible and remained stable in the initial three epochs of the tonic phase in 107 out of 123 (87.0%) seizures. In each epoch, especially the initial one, the contralateral upper limbs were involved more frequently than those ipsilateral to the epileptogenic cortex (p < 0.05). By pairwise comparison, an earlier involvement of the contralateral side to epileptogenic cortex was visually observed in 53 out of 280 (18.9%) limb pairs, in which the ipsilateral limbs were preceded by the contralateral ones 4.6 (0.1–16.0) seconds earlier. Both of the proximal and distal segments were simultaneously involved in 260 out of 298 (87.2%) limb pairs, although the former were 4.3 (0.5–16.0) earlier than the latter in 34 out of 298 (11.4%) limb pairs.

CONCLUSIONS: This study demonstrated that by studying the restricted epileptogenic lesion limited to pure SSMA, unilateral extension and abduction posturing in upper limb were the most prominent and valuable sign for the lesion lateralization in SSMA neurosurgery decision-making.

Keywords

Electro-clinical semiology bilateral asymmetric tonic seizure supplementary sensorimotor area epilepsy (SSMA)image guidance diagnosis Magnetic Resonance Imaging (MRI)

1 Introduction

Supplementary motor area (SMA) seizure was first described by Penfield and Jasper, based on cortical stimulation studies in primates, and later in humans undergoing surgery for medically intractableseizures, Penfield and Welch,delineated the anatomy of the SMA. A sensory function of the SMA was also already proposed by Penfield and Jasper, and was also confirmed by few electrical stimulation studies. Therefore then the term supplementary sensorimotor area (SSMA) was introduced by Lueders. And specifically speaking, the supplementary sensorimotor area (SSMA) is located predominantly in the mesial portion of superior frontal gyrus, confined by the cingulate sulcus inferiorly and by the sensory motor strip posteriorly [1 –3]. Cortical stimulation studies have suggested that SSMA extends onto the dorsolateral aspect of the superior frontal gyrus [4, 5]. It has been shown participate in several aspects of motor control, including movement selection, preparation, initiation, execution, and feedback-monitoring of a motor program as well as in speech [1 , 7].

As regard to seizures, although SSMA seizure was not defined in the seizure classification by International League Against Epilepsy (ILAE) in which “supplementary motor seizure” was described as one of the seizure types in frontal lobe epilepsy manifesting “postural, focal tonic with vocalization, speech arrest, and fencing postures.” It was also commented that multiple frontal areas may be involved rapidly, and specific seizure types may not be discernible. Usually, SSMA seizures are of brief duration, lasting only 10–40 s with rapid onset of asymmetric tonic posturing involving both extremities.

Although there are many well documented cases of SSMA seizures, characterized by the similar manifestations caused by cortical stimulation, cases of real SSMA epilepsy are very rare. By saying real SSMA epilepsy, we mean that SSMA is the epileptogenic zone, not just the symptomatogenic zone [2]. Among surgical candidates for intractable SSMA seizures, frontal cortex other than SSMA or even parietal cortex can be epileptogenic [6, 8]. On the other hand, lack of quantitative approach makes research on semiology of SSMA epilepsy limited. Therefore, a detailed seizure semiology originated primarily from SSMA needs to be reviewed systematically. From the review results, we identified six patients with a single epileptogenic lesion localized in SSMA. The lesions were detected and confirmed by pre- and post- surgery MRI, which is a routine imaging procedure used in current clinical practice [9]. All patients had a long term outcome of being seizure-free after surgery (i.e., focus resection and long-term follow-up period up to 35 months.).

While bilateral asymmetric tonic seizure (BATS) is the most prominent type of the seizures in supplementary sesorimotor area (SSMA) epilepsy, nuances of the seizure semiology have been disclosed only in few cases. For this reason, we systemically reviewed the seizure semiology and comparative MRI (pre- and post- surgery MRI) and found that the limbs of contralateral side to epileptogenic cortex were affected more frequently than ipsilateral side during the tonic phase. Abduction and extension posturing in the unilateral upper limbs should be a significant lateralization sign for SSMA epilepsy. This electro-semiology and image guidance diagnosis can be of great significance for lesion lateralization: For the patients with SSMA epilepsy, both proximal and distal segments of four extremities can become tonic during BATS, while unilateral extension and abduction posturing in upper limb can be the most prominent and valuable sign for lateralization.

2 Materials and methods

In this retrospective study, the study protocol was reviewed and approved by the Ethics Committee of our Medical University. We then retrieved and reviewed existing clinical data involving 386 patients who received epilepsy surgery in the San Bo Brain Hospital, Capital Medical University, Beijing, in between February 2009 and February 2011. Six out of these 386 patients were screened out and confirmed to have a single restricted epileptogenic lesion in SSMA. Demographics of the enrolled subjects were summarized in Table 1.

Presurgical evaluation included detailed clinical history, physical examination, audio-video scalp EEG monitoring and 1.5 Tesla MRI scan, regular and specially orientated. Patient 1 and 2 underwent special thinner MRI scanning to confirm their subtle lesions. All enrolled patients fulfilled the criteria as followings:

MRI showed a single and localized lesion in the SSMA (e.g., Fig. 1), which did not exceed the typical anatomical landmarks as we mentioned above. In sagittal views, the posterior border of SSMA also was in consistent with the vertical line through the posterior commissure (VPC), which was perpendicular to the anterior commissure – posterior commissure (AC-PC) line. Therefore, the lesion was reconfirmed been localized between VPC and genu of corpus callosum in thisview [5].

Free from seizure was the long term outcome after tailored resection of the SSMA lesions [10, 11]. (3) In order to confirm a subtle MRI lesion as epileptogenic, three patients received intracranial recordings (stereo-electroencephalography, SEEG) which verified the seizure onset zone localized at the contacts within SSMA.

In this study, data of long-term monitoring video EEG was independently analyzed by at least two experienced specialists. Visual analysis was the major approach in electroclinical semiology evaluation. If each tonic phase was equally subdivided into ten epochs, one epoch would compose with ten percent of the full time length. As expected, there would be 11 observation points from the ten epochs of time length, if the onset point was included. The sign of tonic contraction being firstly visible on video recording was considered as the onset point of BATS. Otherwise, each rest of the ten points would represent an individual observation value from the ten epochs during the tonic phase. Involvement of BATS with four extremities (upper and lower limbs) was comparatively evaluated between contralateral and ipsilateral sides (to the ictal onset), proximal and distal segments, and upper and lower limbs.

One type of limb pairs between two mirror parts of four extremities was determined, while the other type between upper and lower limbs in the same side was decided. The proximal segment was composed of shoulder and elbow joints in upper limbs, and hip and knee joints in lower limbs. The distal segment consisted of wrist and finger in upper limbs, and ankle and toe in lower limbs. The proximal and distal segments of the same limb were paired for comparison.

Video recordings for the above corresponding limbs without sufficient coverage were eliminated from limb-paired comparison but reserved for frequency evaluation in our study. Additionally, limitations of the visual analysis made it sometimes impossible to determine whether a motionless segment of limb was tonic or not occasional. On this occasion, the seizures which could not be defined on the limb segments involvement with concordance between two video reviewers were not included in the frequency evaluations, so the number of seizures registered for each segment was not identical. Thus, we used a normalized descriptive (proportion of seizures (seizure %)) to enable frequency comparison between different limbs, segments and sides.

Taken together, the electro-clinical features of asymmetric posturing, abduction, extension, flexion and tonic activities (contraction) in different limb-segments (including shoulder, elbow, hip, knee and different axial parts et al.) were analyzed. Moreover, the timing and evolution course (onset point, peak level, lowest level of the proportion of seizures) was also analyzed in detail.

Last, statistical semiologic findings were compared between different extremities (upper/lower), segments of limbs, lateralization side using Fisher’s exact test and One-way ANOVA analysis. Chi-square Test and Mann-Whitney U Test were also conducted for statistical analysis (e.g., age, duration of seizure, seizure frequency were taken into account).

A p value less than 0.05 was considered to be statistically significant.

3 Results

A total of 170 clinical seizures and 13 EEG seizures were registered from the six patients during pre-surgical evaluation. General epileptic data were summarized in Table 2. Finally, 123 seizures were enrolled and 47 seizures were eliminated according to the enroll criteria for video coverage mentioned above.

Based on the semiological seizure classification, the relatively common types of seizures in our series with SSMA epilepsy were observed as followings: aura (56/123 seizures from two patients), autonomic abnormalities (112/123 seizures from five patients), tonic activities with bilateral asymmetric tonic posturing or BATS (123/123 seizures from six patients), tonic-clonic activities (unilateral in 3/123 seizures from two patients, bilateral in 46/123 seizures from one patient), hypermotor behaviors (6/123 seizures from one patient) and automotor behaviors (15/123 seizures from one patient). As expected, like in other studies, the most common semiological patterns of the seizures were BATS with preserved consciousness as previously described [1 , 13].

3.1 Electroclinical features of asymmetric posturing

The most common electroclinical semiology was bilateral asymmetric tonic posturing in which an abduction of the shoulder contralateral to epileptogenic cortex was observed in 123/123 (100%) seizures from six patients and an extension of the elbow contralateral to epileptogenic cortex in 118/123 (95.9%) seizures from six patients, while ipsilaterally, the shoulder abduction was seen in 93/123 (75.6%) seizures from six patients and the elbow flexion in 96/123 (78.0%) seizures from five patients. However, a remarkable extension of the ipsilateral elbow was detected only in one among the 123 seizures. During seizure evolution, this kind of fencing posture started to be visible and remained unchanged in the first three epochs in 87.0% (107/123) seizures, but no later than the fifth epoch.

Compared to the upper limbs, posturing in the lower limbs was not constant or even paradoxical. Contralateral to epileptogenic cortex, an abduction of the hip in 22/123 (17.9%) seizures and an adduction in 54/123 (43.9%) seizures from three patients were observed. Extension of the knee in 56/123 (45.5%) seizures from five patients and flexion in 19/123 (15.4%) seizures from two patients were recorded from the lower limbs. Transition from flexion to extension in the lower extremities occurred in five seizures from two patients. In the ipsilateral lower limbs, posturing were kept abduction of the hip in 15/123 (12.2%) seizures from three patients, while adduction in 57/123(46.3%) seizures from two patients. Extension and flexion of the knee were respectively detected in 22/123 (17.9%) seizures from three patients and 48/123 (39.0%) seizures from the other three patients. Tonic activities in different axial parts were recorded in 111/123 (90.2%) seizures from four patients.

3.2 Different limb-segment involvement during tonic phase

3.2.1 Involvement of the upper limbs

3.2.1.1 Proximal and distal segment of the upper limbs contralateral to ictal onset.

The proportion of seizures presented with tonic activity in the proximal segment of upper limbs contralateral to ictal onset, reached its peak point at 99.2–100% (122–123/123) within the initial two epochs, and remained stable at 97.6% (120/123) until the seventh epoch and then gradually decreased to its lowest level at 89.4% (110/123) in the last epoch (Fig. 2A). Such a high frequency of seizures presented with proximal tonic contraction would imply itself as the most common sign. And a similar trend was observed in distal segment of the upper limbs contralateral to ictal onset (Fig. 3A) (peak level at 98.3% (118/120) in the second epoch, seventh epoch to its lowest level at 85.8% (103/120)).

3.2.1.2 Proximal and distal segment of the upper limbs ipsilateral to ictal onset.

The proportion of seizures, with tonic contraction in proximal segment of the upper limbs ipsilateral side to ictal onset, was significantly lower 71.9% (82/114) than the contralateral side at the first epoch. It reached its peak level at 83.3% (95/114) in the third epoch and the lowest level at 68.4% (78/114) in the last epoch (Fig. 2B). This was also verified by the distal segment of the upper limbs. The proportion of seizures, with tonic contraction in the distal segment of the upper limbs ipsilateral to ictal onset was also significantly lower than the mirror part of the contralateral side (90.0%). As shown in Fig. 3B, it increased to its peak level at 75.2% (79/105) in the fourth epoch, which was one epoch later (compared to the proximal segment) and then decreased from the seventh epoch to its lowest level at 64.7% (68/105) in the end of tonic phase.

3.2.2 Involvement of the lower limbs

3.2.2.1 Proximal and distal segment of the lower limbs contralateral to ictal onset

Compared to the upper limbs as described above, the proportion of seizures with tonic contraction in proximal segment of lower limbs contralateral to ictal onset was relatively lower. It was affected in 79.8% (71/89) of seizures in the first epoch and reached its peak level 93.3% (83/89) in the third epoch and then decreased to a lower level of 80.9% (72/89) in the end (Fig. 4A). And in the distal segment, as shown in Fig. 5A, the proportion increased from 80.5% (62/77) to 93.5% (72/77) in the first three epochs, and showed a gradual downtrend to 79.2% (61/77) in the end of tonic phase.

3.2.2.2 Proximal and distal segment of the lower limbs ipsilateral to tonic ctal onset

As depicted in Fig. 4B, the proportion of seizures, with tonic contraction in proximal segment of the lower limbs ipsilateral to ictal onset, started to increase from 68.6% (59/86) to 77.9% (67/86) in the first three epochs, and declined gradually afterwards and reached its lowest level at 63.9% (55/86) in the last epoch. As to the distal segment, the proportion, increased from 65.0% (26/40) at the beginning to its peak point at 75.0% (30/40) within the initial three epochs. Then it declined by 12% within the next two epochs and reached its lowest level at 52.5% (21/40) in the last epoch (Fig. 5B).

3.3 Comparison between contralateral and ipsilateral sides

Contralateral to the epileptogenic cortex, both proximal and distal limb parts were involved more frequently than those of the ipsilateral side during the whole tonic phase (Figs. 2–6, p < 0.05). As shown in Table 3, the proportion of seizures presented with tonic contraction in proximal segment of the contralateral upper and lower limbs, was 89–100% and 80–93% respectively, while the proportions were 68–83% and 64–78% in that of the ipsilateral upper and lower limbs.

Considering the importance of initial seizure semiology in lateralization, we made a comparison on the data from the onset point. It turned out that the contralateral upper limbs were affected in 90–99% of the seizures and the ipsilateral upper limbs in 47–72% (Tables 3 and 4, p < 0.05). The situation in lower limbs was different from the upper limbs though. Tonic contraction in the contralateral segments at the onset point was observed in higher proportion of seizures but failed to reach statistical significance (Table 4, p > 0.05). Moreover, there might be cases where some proximal segments were not affected at all during one entire seizure process. Our observations showed that, this case did not occur in the contralateral upper arms, in other words the contralateral upper arms were somehow affected by tonic activity to varying degrees in all the 123 BATS. In comparison, while in the ipsilateral upper arms, tonic activity had not been observed at all in 14.9% of the 123 BATS. That is to say, there were significant differences between contralateral and ipsilateral limbs in the proportion of seizures presented with no tonic contraction, with ipsilateral limbs of the epileptogenic cortex having the higher rate to spare (p < 0.05) in the whole tonic phase (Table 5).

3.4 Comparison between proximal and distal segments

At the onset point, the proximal segments of upper limbs were affected more frequently than the distal according to the seizure rate as seen in Figs. 2 and 3 and Table 4 (p < 0.05). For the lower limbs, no difference between the proximal and distal segments was found from either side at the onset point (Figs. 4 and 5 and Table 4, p > 0.05). The proportion of seizure with proximal involvement was variable in different epoch of the tonic phase.

During the entire tonic phase, in the contralateral limbs of epileptogenic cortex, there were no statistical differences between the proximal and distal segments in terms of seizure rate (Fig. 6, p > 0.05), while the findings in the ipsilateral limbs were different (Fig. 6, p < 0.05). In the upper limbs, seizure rate associated with proximal involvement was 68–83% ipsilaterally, while that of the distal involvement was 47–75% ipsilaterally. As for the lower limbs, the proportion of seizures with proximal tonic contraction was 64–78% ipsilaterally, while that of distal tonic contraction was 53–75% ipsilaterally (Table 3).

3.5 Comparison between different limb pairs for temporal relationship (timing and evolution course)

Limbs contralateral to epileptogenic cortex started to be tonic 4.6 (0.1–16.0) seconds earlier than the ipsilateral side, which was visible only in 18.9% (53/280 from four patients) limb pairs. However, this lateralization sign was not discernible in 81.1% (227/280) of the limb pairs. Moreover, the proximal and distal segments were involved simultaneously in a high proportion at 87.2% (260/298) of segment pairs. The proximal segments was involved 4.3 (0.5–16.0) seconds earlier than the distal segment. This delay was only seen in a small proportion (11.4%, 34/298 from five patients) of segment pairs. As a result of the comparative evaluation on the onset of tonic movement, the time difference between the upper and lower limbs was not detectable in 90.5% (228/252 from six patients) limbpairs.

4 Discussion

The Supplementary sensorimotor area (SSMA) plays a significant role in voluntary motor control such as preparation, bimanual coordination, control of motor sequence, and selection of movements [8].Classically, SSMA seizures are characterized by somato-sensitive feelings, asymmetric limb tonic posturing, adverse oculo-cephalic movements, speech arrest or pallilalia, with or without preservation of consciousness [1 , 14]. BATS is the most prominent type of seizures in SSMA epilepsy. This has been proved by cortical simulation studies and many clinical experiences [5, 15], but nuances of the BATS have been disclosed only in a few cases. Although SSMA seizures are rather common, SSMA epilepsy remains an unusual clinical entity [2, 8]. The data of our cases deserve to be noticed, because of a restricted epileptogenic lesion limited to the SSMA for each patient, which is defined by neuroimaging (pre- and post- surgery MR image as clearly shown in Fig. 1) and further confirmed by the seizure free status (up to a long-term follow-up period of 35 months) after focal resection within SSMA.

The ictal clinical semiology observed in our present cases has some typical semiological characteristics of the so-called SSMA seizures. BATS was the most common semiology pattern observed in all six patients. According to general experience with epilepsy localization, we may consider that the unilateral side of extremities, which is involved earlier during seizure, should be extremely important for lateralization. However, SSMA epilepsy is exceptional, because BATS can start with bilateral tonic contraction in four extremities. As seen in our series, this lateralization sign was not discernible in the majority (81.1%) of limb pairs. As a principal feature of BATS, tonic posturing was constant and asymmetric in individual patients, whose upper limbs contralateral to epileptogenic cortex were typically kept in abduction and extension. The posture occurred and remained stable in the first half period of the seizure. On the contrary, no tetanic flexion was observed in the contralateral upper limbs as constant electroclinical semiology in our cases. The postures in the ipsilateral upper arms, which may present as flexion, were not so fixed in the majority of seizures. The limbs in the contralateral side of the epileptogenic cortex were involved more frequently than those in the ipsilateral side during the entire tonic phase, especially at the starting point of seizures. It was also demonstrated that the probability of the ipsilateral limbs not being affected during the tonic phase was higher than that of the contralateral side. In other words, it seemed that a certain number of patients can present with unilateral tonic seizure as reported [1, 12]. We attribute this to a number of factors, e.g., limitation of visual analysis, lack of electromyographic recording, or just a kind of incomplete phenotype of BATS. It has been well accepted that BATS involves more prominently of the proximal and axial parts in the classical description. In the present study, we tried to understand the difference between proximal and distal parts during tonic phase. Firstly, the proximal segments of extremities were involved in advance or at the same time as the distal segment in most cases. Secondly, the proximal segments of upper limbs were involved more frequently than the distal at the starting point. However, it should be emphasized that the distal segments of upper limbs were initially affected in a high proportion of seizures (47% to 90%), meaning that the distal parts can be involved at the very beginning in most of the seizures.

The mechanism underlying bilateral motor activities remains a matter of debate. One of the underlying mechanisms of this phenomenon could be the subcortical activation pattern involved bilateral basal ganglia and contralateral cerebellum, as proved by ictal perfusion from single photon emission computed tomography (SPECT) research [16]. This is also consistent with known projections from SSMA to these areas [2, 16]. Kikuchi et al. found that the responses and the latencies of MEPs (motor evoked potential) in both contra- and ipsi-lateral upper extremities to stimulation of the SSMA indicate the existence of direct descending volleys from the SSMA [17], which means that the unilateral SSMA participates in organization of both pyramidal tracts [18]. Another explanation is that SSMA of one hemisphere is connected with the opposite SSMA, and with the opposite premotor cortex and cingulate gyrus, through transcallosal connections [19]. Some studies suggested that SSMA has relatively dense callosal connections compared to the primary motor cortex. Single shock stimulation studies evoked shorter transcallosal latencies in an order of 10 ms between homologous SSMA sites compared with longer latencies of 30–40 ms between prefrontal sites [20]. All the brain networks as described above would help explain the bilateral motor activity, even at initial stage, in the BATS generated from unilateral SSMA activation. In conclusion, the seizure semiology of BATS from the patients with supplementary sensorimotor area epilepsy was systemically reviewed. The limbs, including both proximal and distal segments, contralateral side to epileptogenic cortex were affected more frequently than ipsilateral side during BATS. Abduction and extension posturing in the unilateral upper limbs should be a significant lateralization sign for SSMA epilepsy.

5 Conclusions

Our cases (screened out from 386 patients) from the combination application of MRI and neurophysiology (electro-semiology) deserve to draw attention of classical neurologists. By focusing our investigation target only to the restricted epileptogenic lesion limited to pure SSMA (confirmed by comparative operative MRI and long-term follow up), the electro-clinical features of asymmetric posturing, abduction, extension, flexion and tonic activities (contraction) in different limb-segments (including shoulder, elbow, hip, knee and different axial parts et al.) of pure SSMA epilepsy patients were fully analyzed. And we significantly found (under the image guidance diagnosis and electro-semiology analysis) that the limbs of contralateral side to epileptogenic cortex were affected more frequently than ipsilateral side during the tonic phase. In addition, the most important observation is that unilateral extension and abduction posturing in upper limb can be the most prominent and valuable sign for the lesion lateralization in SSMA epilepsy patients’ neurosurgerydecision-making.

Conflict of interest

None of the authors have potential conflicts of interest to be disclosed.

Footnotes

Acknowledgments

This work was supported by Beijing Municipal Natural Science Foundation (Grant No.7122088), Joint Fund for basic and clinical research cooperation project of Capital Medical University (Grant No. 12JL87), Capital health research and development of special (Grant No. 2011-1020-01), National clinical key specialty project (Grant No. SG2011) and the Medical Scientific Research Foundation of Guangdong Province (Grant No. A2016317).

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