YEBEH-04311; No of Pages 5 Epilepsy & Behavior xxx (2015) xxx–xxx
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An evaluation of lateralizing signs in patients with temporal lobe epilepsy Esra Erkoç Ataoğlu a,⁎, İrem Yıldırım b, Erhan Bilir b a b
Department of Neurology, Ministry of Health, Zekai Tahir Burak Women's Health Research and Education Hospital, 06830 Ankara, Turkey Department of Neurology, Gazi University Faculty of Medicine, 06830 Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 13 January 2015 Revised 23 March 2015 Accepted 8 April 2015 Available online xxxx Keywords: Temporal lobe epilepsy Lateralizing value Semiologic signs Long-term video-EEG monitoring
a b s t r a c t Resective epilepsy surgery has been accepted as an effective treatment for patients with medically intractable temporal lobe epilepsy (TLE) to control the seizures and to limit cognitive dysfunction. Complete resection of the epileptic zone, and therefore the success of the surgery, depends on the identification of the seizure focus. Reliable lateralizing semiologic signs, together with other presurgical assessments, are of great importance for an accurate identification of the seizure focus. In this respect, this study evaluated the frequency of semiologic signs in medically intractable temporal lobe epilepsy (TLE) together with the lateralizing values and variations according to the age and gender groups. Two hundred seventy-three seizures of 55 patients of the Adult Epilepsy Monitoring Unit of Gazi University Faculty of Medicine with the diagnosis of medically intractable TLE, whose epileptic foci were detected through noninvasive presurgical procedures and seizures were controlled successfully after anterior temporal lobectomy (ATL), were analyzed retrospectively. Seizure semiologies of the patients were evaluated in terms of lateralizing values, and it was inquired whether age/gender causes any variation. Versive head rotation, unilateral dystonic limb posturing, asymmetric tonic limb posturing, and the combination of unilateral hand automatisms and dystonic posturing were determined as the semiologic signs with the highest lateralizing values (90–100%). While hand automatisms were observed frequently in the group with early seizure-onset age (onset age ≤ 2), asymmetric tonic limb posturing was detected as more frequent in the group with later seizure-onset age (onset age N 2; p b .005). In addition to this, semiologic signs were noted to be different between male and female groups; psychic and autonomic auras and ictal emotional signs were associated with women (p b .005). © 2015 Elsevier Inc. All rights reserved.
1. Introduction Temporal lobe epilepsy (TLE) is considered to be the most frequent cause of partial epilepsy in adults, and a large number of patients with TLE especially mesial TLE [MTLE] have seizures that are resistant to antiepileptic drugs. Resective epilepsy surgery, however, stands out as a highly effective treatment for this group. The success of resective epilepsy surgery depends on the accurate identification of the epileptogenic zone [1,2]. Recognition of semiological lateralizing signs during seizures is important in the presurgical evaluation of the patients and adds further information to interictal–ictal EEG, neuroimaging, functional mapping, and neuropsychological evaluation. Ictal semiology analysis, in this respect, is of crucial importance for the lateralization and localization of the epileptic focus. Identification of reliable lateralizing signs, especially in cases with MTLE, together with concordant presurgical noninvasive investigations, enables a successful surgical intervention without invasive tests [2–4]. There have been several previous studies which evaluated the frequencies and lateralizing values of semiologic signs. To the best of our ⁎ Corresponding author. Tel.: +90 5327350458; fax: +90 3123124931. E-mail address: [email protected] (E. Erkoç Ataoğlu).
knowledge, in some of these studies, the seizure focus is determined according to the results of EEG, and MRI and clinical findings are assessed accordingly. These results, however, cannot determine the seizure focus definitely, and this might end in a misleading assessment of lateralizing values. The present study aimed to evaluate the frequencies and lateralizing values of seizure semiology signs by observing patients whose epileptic foci are identified definitively through resective epilepsy surgery and successful seizure control. Previous literature that focuses on ictal semiology in different gender groups has reached various results [5–13]. Earlier neuroradiological studies in human and animal models have shown differences in the functional and anatomical organization of the brain between sexes that affects cerebral transmission and connections [6,14]. Considering that a similar difference between sexes should be seen in ictal semiology, this study investigated the variations of lateralizing sings according to gender. Although there are studies that assess semiologic signs in different age groups, studies that compare semiologic features associated with seizure-onset age are few [15–18]. Previous studies have shown that seizure-onset age and, thus, epilepsy duration might have an impact on pathophysiologic mechanisms and might be predictive in drug-resistant seizures [19]. This study, therefore, evaluated semiologic signs according to seizure-onset age.
http://dx.doi.org/10.1016/j.yebeh.2015.04.015 1525-5050/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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2. Materials and methods Among Gazi University Adult Epilepsy Monitoring Unit patients diagnosed with medically refractory MTLE, 55 patients with completed preoperative noninvasive evaluations, identified epileptic foci, and postoperative seizure freedom or a significant decrease in seizure frequency that confirms the suspected epileptic foci were included in this study. Video-EEG monitoring records and reports of those 55 patients were analyzed retrospectively; their clinical histories, personal and family histories, neuroimaging findings, neuropsychological test results, psychiatry consultations, surgical procedures, pathological findings, and postoperative follow-ups were assessed. Presurgically, long-term scalp video-EEG monitoring was performed for all patients until at least three typical seizures were recorded. Video-EEG monitoring was performed with a Telefactor system, with up to 32 channels of EEG recorded continuously, and for electrode placement, the international 10-20 system was used. The patient or the attendant was asked to press the event button when the patient had auras or seizures. Information on whether patients had auras or not and the type of auras were noted together with ictal behavioral patterns, and the frequency and lateralizing values of these were evaluated. Besides, any possible variations in lateralizing signs that can be associated with either sex or seizureonset age were analyzed. Video recordings of seizures were analyzed by two of the authors (E.E.A. and E.B.) who were blinded to the epileptic foci of the patients. Two hundred seventy-three seizures of 55 patients were observed. Information on whether patients had auras and the types of auras (abdominal, auditory, autonomic, gustatory, olfactory, psychic, somatosensory, and visual) that they had were gathered from the patient descriptions on video-EEG monitoring and from medical records. Ictal behavioral characteristics mentioned in the previous literature [2,3,20,21] including behavioral arrest, oroalimentary and genital automatisms, dystonic or tonic limb posturing, versive or nonversive head deviation, postictal nose wiping, ictal vocalization or speaking, periictal vegetative signs (vomiting, urinary urge, coughing, thirst/ drinking), ictal emotional signs (laughing, crying, fear), unilateral eye blinking, last clonic jerk, ictal spitting, ictal aphasia, and postictal paresis were observed in video recordings. Among these, ictal/postictal aphasia, postictal paresis, and ictal eye blinking were not observed as it was not possible to assess these three signs accurately though video-EEG records. The anterior temporal lobectomy (ATL) protocol was performed at the Department of Neurosurgery of Gazi University Medical Hospital for all patients, and only those patients that were seizure-free (Engel 1a), those that had postoperative seizures but had been seizure-free for two years (Engel 1b), and those that had only auras (Engel 1c) in 1–24 months of follow-up were included. The side of the surgery in each case was accepted as the certain epileptic focus. Lateralizing and localizing values of semiologic signs were determined in comparison to the side of the surgical operation. All statistical data were analyzed using Windows SPSS 12.0. The Mann–Whitney U-test was used to evaluate the correlation between clinical lateralizing signs/seizure-onset age and clinical lateralizing signs/sex. The lateralizing values of clinical findings (ipsilateral/contralateral or left/ right TLE) were analyzed through chi-squared and Fischer's exact tests.
3. Results Fifty-five patients (26 female (47.3%) and 29 male (52.7%)) had 273 seizures. The mean age of patients was 28.2 (range: 17–47). Data on seizure-onset age, epilepsy duration, video-EEG monitoring duration, and the number of seizures noted are summarized in Table 1, and risk factor, EEG, neuroimaging, operation, and postoperative outcome data are summarized in Table 2.
Table 1 Characteristics of patients and monitoring. Variable (n = 55)
Range
Average
Age Seizure-onset age Epilepsy duration Monitoring duration Number of seizures
17–47 years old 0–40 years old 2–40 years 2–7 days 1–13
28.2 11.49 17.7 3.54 5.45
3.1. Frequency and lateralizing values of semiologic signs Hand automatism was observed in 44 patients (80%). Of these, 35 (79.5%) had hand automatism that was ipsilateral to the epileptogenic seizure focus (18 right and 17 left) while 9 (20.5%) had bilateral hand automatism. No contralateral case was seen. Hand automatisms had a positive predictive value to be ipsilateral to the seizure focus (p b 0.0001). Unilateral dystonic limb posturing was observed in 33 (60%) patients: contralateral to the seizure focus in 32 (96.9%) and ipsilateral in 1 (3.1%). Unilateral dystonic limb posturing contralateral to the seizure focus had a statistically significant lateralizing value (p b 0.0001). The combination of hand automatism with dystonic limb posturing was observed in 30 (54.5%) patients. In all, hand automatisms were ipsilateral to the seizure focus, while dystonic limb posturing was contralateral. The ipsilateral hand automatism and contralateral dystonic limb posturing combination had a positive predictive value of 100%. Nonversive head rotation was observed in 34 (61.8%) patients. In 25 (73.5%) of them, nonversive head rotation was ipsilateral to the seizure focus; in 5 (14%) of them, it was contralateral; and in 4 (11%) of them, it was both-sided. Thus, nonversive head rotation had a statistically significant lateralizing value associated with the ipsilateral seizure focus (p b 0.05). Versive head rotation was observed in 26 (47.3%) patients: in 25 (96.1%), it was ipsilateral to the seizure focus and in 1 (3.9%), contralateral. As a result, versive head rotation was determined to have a meaningful lateralizing value for the contralateral seizure focus (p b 0.0001). Postictal nose wiping was observed in 19 (34.5%) patients: in 15 (79%), nose wiping was performed with the hand ipsilateral to the seizure focus; in 1 (5.2%), with the hand contralateral to the seizure
Table 2 Risk factor, EEG, neuroimaging, operation and postoperative outcome data. Variable (n = 55)
Number
Frequency (%)
Risk factors Hypoxia Febrile seizures Head trauma CNS infection Family history Kindred marriage
47/55 38/55 38/55 3/55 18/55 11/55
85.5% 69.1% 69.1% 5.5% 32.7% 20%
EEG Lateralized interictal abnormality Lateralized ictal abnormality Lateralized postictal abnormality
40/55 45/55 39/55
72.7% 81.8% 70.9%
Neuroimaging Lateralized MRI abnormality Lateralized PET abnormality
48/55 36/38
87.2% 94.8%
Operation Right ATL Left ATL
24/55 31/55
43.64% 56.36%
Postoperative outcome Engel 1a Engel 1b Engel 1c
48/55 4/55 3/55
87.3% 7.3% 5.4%
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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focus; and in 3 (15.8%), with both hands. Postictal nose wiping, therefore, was lateralized to the ipsilateral seizure focus (p b 0.05). Asymmetric tonic limb posturing was observed in 14 (25.4%) patients. In 11 of them, it was noted as the “figure-4 posture” type. In 3 patients, it was detected as flexion in one extremity and as extension in the other one yet not “figure-4 posture”. In 13 out of 14 patients, the extremity where flexion developed during the asymmetric tonic posturing was ipsilateral to the seizure focus and it had a meaningful lateralizing value (p = 0.001). When the patients with “figure-4 posture” were taken into account separately, it was seen that in 10 (90.9%) out of 11 patients with “figure-4 posture”, the extremity where flexion was observed was ipsilateral to the seizure focus similarly, thus giving a meaningful lateralizing value. In relation to ictal speaking, 8 (14.5%) patients were observed to have meaningful speaking during the seizure. Right TLE was diagnosed in 7 (87.5%) of them, while left TLE was the diagnosis in 1 (12.5%) patient. Ictal speaking was associated with right TLE and had a significant lateralizing value (p = 0.007). Periictal urinary urge was observed in 3 patients (5.4%) during the seizure and early postictal period. All 3 had right TLE; thus, urinary urge statistically significantly related to right TLE (p = 0.043). Ictal vocalization was detected in 19 (34.5%) patients, and 6 (31.5%) of them were noted to have right TLE while 13 (68.5%) had left TLE. Despite the fact that ictal vocalization appears to be related to left TLE, a statistically significant lateralizing value was not found. Periictal behavioral arrest, oroalimentary automatism, ictal coughing, ictal fear, ictal crying, ictal laughing, ictal vomiting, periictal water drinking, and genital automatisms were other semiologic findings noted in this study, but their lateralizing values were not statistically significant. The lateralizing values of auras were also examined. Out of the auras defined in the patient group, somatosensorial auras, abdominal auras, and psychic auras were noted not to have meaningful lateralizing values. Although autonomic auras seemed to be related to right TLE, this relation was not statistically significant. An olfactory aura was defined by 3 (5.5%) patients, and right TLE was detected in all. The olfactory aura and right TLE relationship was statistically significant (p = 0.043). Tables 3 and 4 summarize the frequency and lateralizing values of the semiologic seizure signs.
3.2. The comparison of lateralizing signs in gender groups Out of 55 patients that were included in this research, 26 were female (47.3%) and 29 were male (52.7%). All semiologic signs of which frequencies and lateralizing values were investigated were examined for female and male groups separately (Table 5). Psychic auras were mentioned by 23 (41.8%) patients. Fifteen (65.2%) of them were female and 8 (34.8%) were male, indicating that psychic auras were seen in female patients more frequently. The
Frequency %
n
Nonversive head rotation Versive head rotation Asymmetric tonic posture Dystonia Hand automatism Hand automatism + dystonia
61.8% 47.3% 25.4% 60% 80% 54.5%
34/55 26/55 14/55 33/55 44/55 30/55
Nose wiping Genital automatism
34.5% 3.6%
19/55 2/55
NS, not significant at the .05 significance level. ⁎ p b .05.
Table 4 Frequency and lateralizing values of semiologic signs. Clinical sign
Frequency
Periictal behavioral arrest Oroalimentary automatism Ictal vocalization Ictal speaking Ictal coughing Periictal water drinking Ictal vomiting Periictal urinary urge Ictal crying Periictal fear Ictal laughing Autonomic auras Somatosensorial auras Olfactory auras Abdominal auras Psychic auras
85.5% 47.3% 34.5% 14.5% 7.3% 1.8% 1.8% 5.4% 3.6% 6.4% 1.8% 9.1% 12.7% 5.5% 25.5% 41.8%
Lateralization
p
Right
Left
42.5% 46% 31.5% 87.5% 50% 100% – 100% 50% 44% – 80% 57.1% 100% 64.3% 39%
57.5% 54% 68.5% 12.5% 50% – 100% – 50% 56% 100% 20% 42.9% – 35.7% 61%
.154 .127 .190 .007⁎ .079 .25 .375 .043⁎ .853 .957 .375 .086 .072 .043⁎ .071 .568
⁎ p b .05.
difference between female and male groups in terms of psychic auras was statistically significant (p = 0.025). Autonomic auras were reported by 5 (9.1%) patients. Since they were all female, it was statistically significant (p = 0.014). Ictal emotional symptoms were reported by 12 patients. Out of them, 8 (30%) were women and 4 (13.7%) were men. It tends to be more frequent in women, though not statistically significant (p = 0.09). In terms of other semiologic signs, no significant difference between gender groups was determined. 3.3. The comparison of lateralizing signs according to seizure-onset age Patients were divided into two groups as those with seizure onset at age 2 and below and those with seizure onset at age above 2, and the difference between the age groups in terms of semiologic signs was examined. Lateralizing signs with differences between the age groups are summarized in Table 6. Asymmetric tonic limb posturing was noted in patients with seizure onset at age above 2 and was not encountered in patients with seizure onset at age 2 and below. This difference was statistically significant (p = 0.045). Oroalimentary automatism was seen more frequently in the group with seizure onset at age 2 and below compared to the group with seizure onset at age above 2, and this was statistically significant (p = 0.023). Hand automatism was observed more frequently in the group with seizure onset at age 2 and below compared to the group with seizure onset at age above 2, and this difference was statistically significant (p = 0.008). 4. Discussion
Table 3 Frequency and lateralizing values of semiologic signs. Clinical symptom
3
Lateralization
p
73.5% ipsilateral 96.1% contralateral 92% ipsilateral to flexion 96.9% contralateral 79.5% ipsilateral 100% contralateral to dystonia 79% ipsilateral 100% ipsilateral
.006⁎ .000⁎ .001⁎ .000⁎ .000⁎ .000⁎ .012⁎ NS
The studies about seizure semiology that include a group of patients who had resective epilepsy surgery, coherent pathological results, and good seizure control which have definitely identified their epileptogenic foci, such as ours, have been accepted as reliable [22–24]. In our study, Table 5 Lateralizing signs with differences between the gender groups. Clinical symptom
Automatic auras Psychic auras Emotional symptoms
Frequency
Female
Male
p (b.05)
%
n
%
n
%
n
9.1% 41.8% 21%
5/55 23/55 12/55
19.2% 57.6% 30.7%
5/26 15/26 8/26
0 27.5% 13.7%
0 8/29 4/29
0.014 0.025 0.09
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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Table 6 Lateralizing signs with differences between the age groups. Clinical symptom
Frequency
Seizure onset at age b 2
Seizure onset at age N 2
%
%
%
n
n
p
n
Hand automatism 80% 44/55 100% 10/10 75.5% 34/45 .008 Oroalimentary automatism 47.3% 26/55 80% 8/10 40% 18/45 .023 Asymmetric tonic posture 25.4% 14/55 0 0/10 31.1% 14/45 .045
it was not possible to access the pathological results of all patients. However, postoperative seizure freedom has been accepted as the gold standard for the identification of the epileptogenic zone [3], which our study fulfilled. Successful seizure control (Engel 1) in almost all cases of this study, therefore, indicates accurate identification of the seizure focus. This study identified versive head rotation, unilateral dystonic limb posturing, asymmetric tonic limb posturing, and unilateral dystonic limb posturing–hand automatism combination as the most reliable semiologic signs (lateralizing values: 90–100%) for lateralizing the seizure focus. The results of this study confirm the results presented by previous research [3,22]. Previous studies have revealed controversial results in terms of the reliability of head deviation as a clinical finding for lateralization, and the contradictory results have been explained by the subjectivity of the evaluation of head rotations by the researchers [22]. Versive and nonversive head deviations were identified differently in each study, and in some studies, the seizure phase in which the head deviation occurs was also taken into consideration [22–26]. In this study, versive head deviation was defined as a head deviation that is persistent, larger than 45 degrees, and coupled with neck extension. Only versive head deviations that were observed just before secondarily generalized seizures were taken into account, and any deviations that occurred in other phases of the seizure were ignored. Nonversive head deviation was defined as a softer, nonforcing, more natural head movement, and short or very narrowangle head deviations were ignored. The differences in research populations might be another reason for the conflicting results in terms of the reliability of head deviation as a clinical finding for lateralization. The studies that include only patients with TLE may find different lateralization results for head deviation compared to other studies that include patients with different types of partial epilepsies. This difference in results can be explained through differences in seizure spread patterns. According to the results of this study, in patients with TLE with drug-resistant seizures, nonversive head rotation was 73% ipsilateral to the seizure focus, and versive head rotation that was observed before secondarily generalized seizures was 100% contralateral. These findings confirm the results of Marks and Laxer and Kotagal et al. [22,23]. The similarity in results might be explained through the usage of similar criteria in identifying versive and nonversive head movements. Various previous studies could not determine the lateralizing values of auras [20,22,27]. Guptka et al., however, claimed that autonomic and psychic auras are associated with a right temporal focus [28]. This study did not determine a lateralizing value for psychic auras. Autonomic auras, on the other hand, were associated with right TLE, similar to the results of Guptka et al. The result that this study reached in terms of autonomic auras was not statistically significant; however, the association of autonomic auras with right TLE indicates that similar research conducted on larger groups of patients might reach decisive results. Autonomic auras might be associated with right TLE, as the autonomic network lateralizes to the right temporal lobe [29,30]. This study indicates that olfactory auras can be associated with right TLE, which has not been suggested by the previous studies. Again, it is believed that research conducted on larger series of patients might result more definitive results.
This study indicates that ictal speech has a lateralizing value for the right temporal lobe, and this result confirms previous studies. Ictal vocalization might be associated with the left temporal lobe; however, this association has a low statistical value and, thus, is not meaningful result. In terms of vegetative symptoms such as ictal coughing, urinary urge, vomiting, and drinking, it can be stated that, similar to the results of the previous studies, these are found to be rare and, thus, do not present clinically useful lateralizing values [29]. Various studies have been conducted on periictal fear, which is an ictal emotional symptom, and it has been shown that this symptom does not have a lateralizing value [31–33]. This study, likewise, did not reach a meaningful result in terms of ictal fear, laughing, or crying. This study evaluated semiologic signs according to seizure-onset age as seizure-onset age and, thus, epilepsy duration might have an impact on pathophysiologic mechanisms and might be predictive in drug-resistant seizures. Previous research that made similar evaluations of semiologic signs according to seizure-onset age accepted 18 as the level for determining early or late age at seizure onset [19]. Other studies [34,35] have claimed the seizures of patients N6 years of age to be similar to the seizures of adults and seizure semiology of infants and children to be quite different. Similarly, Olbrich et al. [17], in their study that compared clinical lateralizing signs in infant–child and adolescent groups, found significant differences between these groups. Considering the importance of the first years in terms of seizure features as has been indicated by the previous literature, this study accepted 2 as the age level and reached the conclusion that oroalimentary automatism is statistically significantly more frequent in the patient group with seizure onset at age ≤ 2 years old (average epilepsy duration: 23.7 years) when compared to the patient group with seizure onset at age N 2 years old (average epilepsy duration: 15.43 years). This result can be explained by a more distinct hippocampal sclerosis that emerged as a result of longer epilepsy duration. In addition, the present study also found out that asymmetric tonic limb posturing, which is a complex automatism, is statistically significantly more frequent in the patient group with later seizure-onset age. This result, which is a similar one to that found by previous studies, suggests that complex automatisms can be associated with brain maturation; the more mature the brain becomes, the more that complex symptomatology emerges [17, 36]. This study did not find any other difference between different age groups and, thus, supports that view that auras and emotional and psychical symptoms are not bound to age [32]. Further studies that consider larger patient groups would certainly reveal more conclusive results. Previous studies have linked gender differences to the functional and anatomical organization of temporal structures. The results of this study indicated that emotional signs are more frequent in women than in men. Similarly, Meletti et al. have indicated that in their study, emotional responses were more frequent in women than in men [12]. In addition to this, Chiesa et al. have shown that there is a female predominance in terms of ictal fear and also concluded that this predominance of women is even more distinct in adults [5]. Studies conducted on human and animal models have shown the critical role of the amygdala in emotional stimulation memory. It has also been argued that the amygdala, in terms of its relation to emotional stimulation memory, has a gender-associated lateralizing value [13]. In addition to differences in amygdala response in men and women, the structure of the amygdala is also different in different sexes. Hormonal or sociocultural effects might also have a role in the differences of emotional expressions between male and female patients. The gradual increase in the differences of emotional expressions between sexes from childhood to adulthood also strengthens the idea that these differences occur during maturation [37]. It should also be considered that women tend to express their feelings more often than men, and this could potentially explain the difference in the frequency of ictal emotional symptoms between men and women. As an addition to
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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physiopathological explanations, it should be considered that adult males tend to ignore or suppress their feelings [5]. This speculative point certainly needs further research. This study included only patients with TLE with drug-resistant seizures; therefore, the results might not be representative for all TLE populations. Clinical lateralizing signs, however, can only be assessed in detail in patient groups that can be monitored by video-EEG. A similar restriction, therefore, is applicable to all studies which evaluate lateralizing signs. 5. Conclusion In conclusion, some frequently observed semiologic signs can lateralize the seizure focus at a very highly reliable rate and have important guiding values preoperatively. Further, lateralizing values differ according to gender and seizure-onset age as these might reveal crucial information about pathophysiological mechanisms. Finally, lateralizing values of rare semiologic signs are hard to determine await future studies with larger numbers of patients. Conflict of interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this paper is consistent with those guidelines. References [1] Elger CE, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy Behav 2008;12:501–5392. [2] Noachtar S, Peters AS. Semiology of epileptic seizures: a critical review. Epilepsy Behav 2009;15:2–9. [3] Loddenkemper T, Kotagal P. Lateralizing signs during seizures in focal epilepsy. Epilepsy Behav 2005;7:1–17. [4] Karataş A, Aksoy Ö, Bilir E, Erdem A. Yetişkinlerde Epilepsi Cerrahisi: Cerrahi Öncesi Değerlendirmeler ve Cerrahi Yöntemler. Nöroloji Dergisi 2004;2(2):152–60. [5] Chiesa V, Gardella E, Tassi L, Canger R, Lo Russo G, Piazzini A, et al. Age-related gender differences in reporting ictal fear: analysis of case histories and review of the literature. Epilepsia 2007;48(12):2361–4. [6] Tezer FI, Kurne A, Soylu AR, Saygi S. Effects of lateralisation and gender on temporal lobe ictal behavior associated with hippocampal sclerosis. Seizure 2004;13:418–24. [7] Santana MTCG, Jakowski AP, Britto FS, Sandim GB, Caboclo LOSF, Centeno RS, et al. Gender and hemispheric differences in temporal lobe epilepsy: a VBM study. Seizure 2014;23:274–9. [8] Toth V, Fogarasi A, Karadi K, Kovacs N, Ebner A, Jansky J. Ictal affective symptoms in temporal lobe epilepsy are related to gender and age. Epilepsia 2010;51(7): 1126–32. [9] Savic I, Engel Jr J. Sex differences in patients with mesial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998;65:910–2. [10] Janszky J, Schulz R, Janszky I, Ebner A. Medial temporal lobe epilepsy: gender differences. J Neurol Neurosurg Psychiatry 2004;75:773–5. [11] Doherty MJ, Rostad SW, Abson Kraemer DL, Vossler DG, Haltiner A. Neocortical gliosis in temporal lobe epilepsy: gender-based differences. Epilepsia 2007;48(8):1455–9. [12] Meletti S, Tassi L, Mai R, Fini N, Tassinari CA, Russo GL. Emotions induced by intracerebral electrical stimulation of the temporal lobe. Epilepsia 2006;47(5):47–51.
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Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
An evaluation of lateralizing signs in patients with temporal lobe epilepsy Esra Erkoç Ataoğlu a,⁎, İrem Yıldırım b, Erhan Bilir b a b
Department of Neurology, Ministry of Health, Zekai Tahir Burak Women's Health Research and Education Hospital, 06830 Ankara, Turkey Department of Neurology, Gazi University Faculty of Medicine, 06830 Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 13 January 2015 Revised 23 March 2015 Accepted 8 April 2015 Available online xxxx Keywords: Temporal lobe epilepsy Lateralizing value Semiologic signs Long-term video-EEG monitoring
a b s t r a c t Resective epilepsy surgery has been accepted as an effective treatment for patients with medically intractable temporal lobe epilepsy (TLE) to control the seizures and to limit cognitive dysfunction. Complete resection of the epileptic zone, and therefore the success of the surgery, depends on the identification of the seizure focus. Reliable lateralizing semiologic signs, together with other presurgical assessments, are of great importance for an accurate identification of the seizure focus. In this respect, this study evaluated the frequency of semiologic signs in medically intractable temporal lobe epilepsy (TLE) together with the lateralizing values and variations according to the age and gender groups. Two hundred seventy-three seizures of 55 patients of the Adult Epilepsy Monitoring Unit of Gazi University Faculty of Medicine with the diagnosis of medically intractable TLE, whose epileptic foci were detected through noninvasive presurgical procedures and seizures were controlled successfully after anterior temporal lobectomy (ATL), were analyzed retrospectively. Seizure semiologies of the patients were evaluated in terms of lateralizing values, and it was inquired whether age/gender causes any variation. Versive head rotation, unilateral dystonic limb posturing, asymmetric tonic limb posturing, and the combination of unilateral hand automatisms and dystonic posturing were determined as the semiologic signs with the highest lateralizing values (90–100%). While hand automatisms were observed frequently in the group with early seizure-onset age (onset age ≤ 2), asymmetric tonic limb posturing was detected as more frequent in the group with later seizure-onset age (onset age N 2; p b .005). In addition to this, semiologic signs were noted to be different between male and female groups; psychic and autonomic auras and ictal emotional signs were associated with women (p b .005). © 2015 Elsevier Inc. All rights reserved.
1. Introduction Temporal lobe epilepsy (TLE) is considered to be the most frequent cause of partial epilepsy in adults, and a large number of patients with TLE especially mesial TLE [MTLE] have seizures that are resistant to antiepileptic drugs. Resective epilepsy surgery, however, stands out as a highly effective treatment for this group. The success of resective epilepsy surgery depends on the accurate identification of the epileptogenic zone [1,2]. Recognition of semiological lateralizing signs during seizures is important in the presurgical evaluation of the patients and adds further information to interictal–ictal EEG, neuroimaging, functional mapping, and neuropsychological evaluation. Ictal semiology analysis, in this respect, is of crucial importance for the lateralization and localization of the epileptic focus. Identification of reliable lateralizing signs, especially in cases with MTLE, together with concordant presurgical noninvasive investigations, enables a successful surgical intervention without invasive tests [2–4]. There have been several previous studies which evaluated the frequencies and lateralizing values of semiologic signs. To the best of our ⁎ Corresponding author. Tel.: +90 5327350458; fax: +90 3123124931. E-mail address: [email protected] (E. Erkoç Ataoğlu).
knowledge, in some of these studies, the seizure focus is determined according to the results of EEG, and MRI and clinical findings are assessed accordingly. These results, however, cannot determine the seizure focus definitely, and this might end in a misleading assessment of lateralizing values. The present study aimed to evaluate the frequencies and lateralizing values of seizure semiology signs by observing patients whose epileptic foci are identified definitively through resective epilepsy surgery and successful seizure control. Previous literature that focuses on ictal semiology in different gender groups has reached various results [5–13]. Earlier neuroradiological studies in human and animal models have shown differences in the functional and anatomical organization of the brain between sexes that affects cerebral transmission and connections [6,14]. Considering that a similar difference between sexes should be seen in ictal semiology, this study investigated the variations of lateralizing sings according to gender. Although there are studies that assess semiologic signs in different age groups, studies that compare semiologic features associated with seizure-onset age are few [15–18]. Previous studies have shown that seizure-onset age and, thus, epilepsy duration might have an impact on pathophysiologic mechanisms and might be predictive in drug-resistant seizures [19]. This study, therefore, evaluated semiologic signs according to seizure-onset age.
http://dx.doi.org/10.1016/j.yebeh.2015.04.015 1525-5050/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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2. Materials and methods Among Gazi University Adult Epilepsy Monitoring Unit patients diagnosed with medically refractory MTLE, 55 patients with completed preoperative noninvasive evaluations, identified epileptic foci, and postoperative seizure freedom or a significant decrease in seizure frequency that confirms the suspected epileptic foci were included in this study. Video-EEG monitoring records and reports of those 55 patients were analyzed retrospectively; their clinical histories, personal and family histories, neuroimaging findings, neuropsychological test results, psychiatry consultations, surgical procedures, pathological findings, and postoperative follow-ups were assessed. Presurgically, long-term scalp video-EEG monitoring was performed for all patients until at least three typical seizures were recorded. Video-EEG monitoring was performed with a Telefactor system, with up to 32 channels of EEG recorded continuously, and for electrode placement, the international 10-20 system was used. The patient or the attendant was asked to press the event button when the patient had auras or seizures. Information on whether patients had auras or not and the type of auras were noted together with ictal behavioral patterns, and the frequency and lateralizing values of these were evaluated. Besides, any possible variations in lateralizing signs that can be associated with either sex or seizureonset age were analyzed. Video recordings of seizures were analyzed by two of the authors (E.E.A. and E.B.) who were blinded to the epileptic foci of the patients. Two hundred seventy-three seizures of 55 patients were observed. Information on whether patients had auras and the types of auras (abdominal, auditory, autonomic, gustatory, olfactory, psychic, somatosensory, and visual) that they had were gathered from the patient descriptions on video-EEG monitoring and from medical records. Ictal behavioral characteristics mentioned in the previous literature [2,3,20,21] including behavioral arrest, oroalimentary and genital automatisms, dystonic or tonic limb posturing, versive or nonversive head deviation, postictal nose wiping, ictal vocalization or speaking, periictal vegetative signs (vomiting, urinary urge, coughing, thirst/ drinking), ictal emotional signs (laughing, crying, fear), unilateral eye blinking, last clonic jerk, ictal spitting, ictal aphasia, and postictal paresis were observed in video recordings. Among these, ictal/postictal aphasia, postictal paresis, and ictal eye blinking were not observed as it was not possible to assess these three signs accurately though video-EEG records. The anterior temporal lobectomy (ATL) protocol was performed at the Department of Neurosurgery of Gazi University Medical Hospital for all patients, and only those patients that were seizure-free (Engel 1a), those that had postoperative seizures but had been seizure-free for two years (Engel 1b), and those that had only auras (Engel 1c) in 1–24 months of follow-up were included. The side of the surgery in each case was accepted as the certain epileptic focus. Lateralizing and localizing values of semiologic signs were determined in comparison to the side of the surgical operation. All statistical data were analyzed using Windows SPSS 12.0. The Mann–Whitney U-test was used to evaluate the correlation between clinical lateralizing signs/seizure-onset age and clinical lateralizing signs/sex. The lateralizing values of clinical findings (ipsilateral/contralateral or left/ right TLE) were analyzed through chi-squared and Fischer's exact tests.
3. Results Fifty-five patients (26 female (47.3%) and 29 male (52.7%)) had 273 seizures. The mean age of patients was 28.2 (range: 17–47). Data on seizure-onset age, epilepsy duration, video-EEG monitoring duration, and the number of seizures noted are summarized in Table 1, and risk factor, EEG, neuroimaging, operation, and postoperative outcome data are summarized in Table 2.
Table 1 Characteristics of patients and monitoring. Variable (n = 55)
Range
Average
Age Seizure-onset age Epilepsy duration Monitoring duration Number of seizures
17–47 years old 0–40 years old 2–40 years 2–7 days 1–13
28.2 11.49 17.7 3.54 5.45
3.1. Frequency and lateralizing values of semiologic signs Hand automatism was observed in 44 patients (80%). Of these, 35 (79.5%) had hand automatism that was ipsilateral to the epileptogenic seizure focus (18 right and 17 left) while 9 (20.5%) had bilateral hand automatism. No contralateral case was seen. Hand automatisms had a positive predictive value to be ipsilateral to the seizure focus (p b 0.0001). Unilateral dystonic limb posturing was observed in 33 (60%) patients: contralateral to the seizure focus in 32 (96.9%) and ipsilateral in 1 (3.1%). Unilateral dystonic limb posturing contralateral to the seizure focus had a statistically significant lateralizing value (p b 0.0001). The combination of hand automatism with dystonic limb posturing was observed in 30 (54.5%) patients. In all, hand automatisms were ipsilateral to the seizure focus, while dystonic limb posturing was contralateral. The ipsilateral hand automatism and contralateral dystonic limb posturing combination had a positive predictive value of 100%. Nonversive head rotation was observed in 34 (61.8%) patients. In 25 (73.5%) of them, nonversive head rotation was ipsilateral to the seizure focus; in 5 (14%) of them, it was contralateral; and in 4 (11%) of them, it was both-sided. Thus, nonversive head rotation had a statistically significant lateralizing value associated with the ipsilateral seizure focus (p b 0.05). Versive head rotation was observed in 26 (47.3%) patients: in 25 (96.1%), it was ipsilateral to the seizure focus and in 1 (3.9%), contralateral. As a result, versive head rotation was determined to have a meaningful lateralizing value for the contralateral seizure focus (p b 0.0001). Postictal nose wiping was observed in 19 (34.5%) patients: in 15 (79%), nose wiping was performed with the hand ipsilateral to the seizure focus; in 1 (5.2%), with the hand contralateral to the seizure
Table 2 Risk factor, EEG, neuroimaging, operation and postoperative outcome data. Variable (n = 55)
Number
Frequency (%)
Risk factors Hypoxia Febrile seizures Head trauma CNS infection Family history Kindred marriage
47/55 38/55 38/55 3/55 18/55 11/55
85.5% 69.1% 69.1% 5.5% 32.7% 20%
EEG Lateralized interictal abnormality Lateralized ictal abnormality Lateralized postictal abnormality
40/55 45/55 39/55
72.7% 81.8% 70.9%
Neuroimaging Lateralized MRI abnormality Lateralized PET abnormality
48/55 36/38
87.2% 94.8%
Operation Right ATL Left ATL
24/55 31/55
43.64% 56.36%
Postoperative outcome Engel 1a Engel 1b Engel 1c
48/55 4/55 3/55
87.3% 7.3% 5.4%
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
E. Erkoç Ataoğlu et al. / Epilepsy & Behavior xxx (2015) xxx–xxx
focus; and in 3 (15.8%), with both hands. Postictal nose wiping, therefore, was lateralized to the ipsilateral seizure focus (p b 0.05). Asymmetric tonic limb posturing was observed in 14 (25.4%) patients. In 11 of them, it was noted as the “figure-4 posture” type. In 3 patients, it was detected as flexion in one extremity and as extension in the other one yet not “figure-4 posture”. In 13 out of 14 patients, the extremity where flexion developed during the asymmetric tonic posturing was ipsilateral to the seizure focus and it had a meaningful lateralizing value (p = 0.001). When the patients with “figure-4 posture” were taken into account separately, it was seen that in 10 (90.9%) out of 11 patients with “figure-4 posture”, the extremity where flexion was observed was ipsilateral to the seizure focus similarly, thus giving a meaningful lateralizing value. In relation to ictal speaking, 8 (14.5%) patients were observed to have meaningful speaking during the seizure. Right TLE was diagnosed in 7 (87.5%) of them, while left TLE was the diagnosis in 1 (12.5%) patient. Ictal speaking was associated with right TLE and had a significant lateralizing value (p = 0.007). Periictal urinary urge was observed in 3 patients (5.4%) during the seizure and early postictal period. All 3 had right TLE; thus, urinary urge statistically significantly related to right TLE (p = 0.043). Ictal vocalization was detected in 19 (34.5%) patients, and 6 (31.5%) of them were noted to have right TLE while 13 (68.5%) had left TLE. Despite the fact that ictal vocalization appears to be related to left TLE, a statistically significant lateralizing value was not found. Periictal behavioral arrest, oroalimentary automatism, ictal coughing, ictal fear, ictal crying, ictal laughing, ictal vomiting, periictal water drinking, and genital automatisms were other semiologic findings noted in this study, but their lateralizing values were not statistically significant. The lateralizing values of auras were also examined. Out of the auras defined in the patient group, somatosensorial auras, abdominal auras, and psychic auras were noted not to have meaningful lateralizing values. Although autonomic auras seemed to be related to right TLE, this relation was not statistically significant. An olfactory aura was defined by 3 (5.5%) patients, and right TLE was detected in all. The olfactory aura and right TLE relationship was statistically significant (p = 0.043). Tables 3 and 4 summarize the frequency and lateralizing values of the semiologic seizure signs.
3.2. The comparison of lateralizing signs in gender groups Out of 55 patients that were included in this research, 26 were female (47.3%) and 29 were male (52.7%). All semiologic signs of which frequencies and lateralizing values were investigated were examined for female and male groups separately (Table 5). Psychic auras were mentioned by 23 (41.8%) patients. Fifteen (65.2%) of them were female and 8 (34.8%) were male, indicating that psychic auras were seen in female patients more frequently. The
Frequency %
n
Nonversive head rotation Versive head rotation Asymmetric tonic posture Dystonia Hand automatism Hand automatism + dystonia
61.8% 47.3% 25.4% 60% 80% 54.5%
34/55 26/55 14/55 33/55 44/55 30/55
Nose wiping Genital automatism
34.5% 3.6%
19/55 2/55
NS, not significant at the .05 significance level. ⁎ p b .05.
Table 4 Frequency and lateralizing values of semiologic signs. Clinical sign
Frequency
Periictal behavioral arrest Oroalimentary automatism Ictal vocalization Ictal speaking Ictal coughing Periictal water drinking Ictal vomiting Periictal urinary urge Ictal crying Periictal fear Ictal laughing Autonomic auras Somatosensorial auras Olfactory auras Abdominal auras Psychic auras
85.5% 47.3% 34.5% 14.5% 7.3% 1.8% 1.8% 5.4% 3.6% 6.4% 1.8% 9.1% 12.7% 5.5% 25.5% 41.8%
Lateralization
p
Right
Left
42.5% 46% 31.5% 87.5% 50% 100% – 100% 50% 44% – 80% 57.1% 100% 64.3% 39%
57.5% 54% 68.5% 12.5% 50% – 100% – 50% 56% 100% 20% 42.9% – 35.7% 61%
.154 .127 .190 .007⁎ .079 .25 .375 .043⁎ .853 .957 .375 .086 .072 .043⁎ .071 .568
⁎ p b .05.
difference between female and male groups in terms of psychic auras was statistically significant (p = 0.025). Autonomic auras were reported by 5 (9.1%) patients. Since they were all female, it was statistically significant (p = 0.014). Ictal emotional symptoms were reported by 12 patients. Out of them, 8 (30%) were women and 4 (13.7%) were men. It tends to be more frequent in women, though not statistically significant (p = 0.09). In terms of other semiologic signs, no significant difference between gender groups was determined. 3.3. The comparison of lateralizing signs according to seizure-onset age Patients were divided into two groups as those with seizure onset at age 2 and below and those with seizure onset at age above 2, and the difference between the age groups in terms of semiologic signs was examined. Lateralizing signs with differences between the age groups are summarized in Table 6. Asymmetric tonic limb posturing was noted in patients with seizure onset at age above 2 and was not encountered in patients with seizure onset at age 2 and below. This difference was statistically significant (p = 0.045). Oroalimentary automatism was seen more frequently in the group with seizure onset at age 2 and below compared to the group with seizure onset at age above 2, and this was statistically significant (p = 0.023). Hand automatism was observed more frequently in the group with seizure onset at age 2 and below compared to the group with seizure onset at age above 2, and this difference was statistically significant (p = 0.008). 4. Discussion
Table 3 Frequency and lateralizing values of semiologic signs. Clinical symptom
3
Lateralization
p
73.5% ipsilateral 96.1% contralateral 92% ipsilateral to flexion 96.9% contralateral 79.5% ipsilateral 100% contralateral to dystonia 79% ipsilateral 100% ipsilateral
.006⁎ .000⁎ .001⁎ .000⁎ .000⁎ .000⁎ .012⁎ NS
The studies about seizure semiology that include a group of patients who had resective epilepsy surgery, coherent pathological results, and good seizure control which have definitely identified their epileptogenic foci, such as ours, have been accepted as reliable [22–24]. In our study, Table 5 Lateralizing signs with differences between the gender groups. Clinical symptom
Automatic auras Psychic auras Emotional symptoms
Frequency
Female
Male
p (b.05)
%
n
%
n
%
n
9.1% 41.8% 21%
5/55 23/55 12/55
19.2% 57.6% 30.7%
5/26 15/26 8/26
0 27.5% 13.7%
0 8/29 4/29
0.014 0.025 0.09
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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Table 6 Lateralizing signs with differences between the age groups. Clinical symptom
Frequency
Seizure onset at age b 2
Seizure onset at age N 2
%
%
%
n
n
p
n
Hand automatism 80% 44/55 100% 10/10 75.5% 34/45 .008 Oroalimentary automatism 47.3% 26/55 80% 8/10 40% 18/45 .023 Asymmetric tonic posture 25.4% 14/55 0 0/10 31.1% 14/45 .045
it was not possible to access the pathological results of all patients. However, postoperative seizure freedom has been accepted as the gold standard for the identification of the epileptogenic zone [3], which our study fulfilled. Successful seizure control (Engel 1) in almost all cases of this study, therefore, indicates accurate identification of the seizure focus. This study identified versive head rotation, unilateral dystonic limb posturing, asymmetric tonic limb posturing, and unilateral dystonic limb posturing–hand automatism combination as the most reliable semiologic signs (lateralizing values: 90–100%) for lateralizing the seizure focus. The results of this study confirm the results presented by previous research [3,22]. Previous studies have revealed controversial results in terms of the reliability of head deviation as a clinical finding for lateralization, and the contradictory results have been explained by the subjectivity of the evaluation of head rotations by the researchers [22]. Versive and nonversive head deviations were identified differently in each study, and in some studies, the seizure phase in which the head deviation occurs was also taken into consideration [22–26]. In this study, versive head deviation was defined as a head deviation that is persistent, larger than 45 degrees, and coupled with neck extension. Only versive head deviations that were observed just before secondarily generalized seizures were taken into account, and any deviations that occurred in other phases of the seizure were ignored. Nonversive head deviation was defined as a softer, nonforcing, more natural head movement, and short or very narrowangle head deviations were ignored. The differences in research populations might be another reason for the conflicting results in terms of the reliability of head deviation as a clinical finding for lateralization. The studies that include only patients with TLE may find different lateralization results for head deviation compared to other studies that include patients with different types of partial epilepsies. This difference in results can be explained through differences in seizure spread patterns. According to the results of this study, in patients with TLE with drug-resistant seizures, nonversive head rotation was 73% ipsilateral to the seizure focus, and versive head rotation that was observed before secondarily generalized seizures was 100% contralateral. These findings confirm the results of Marks and Laxer and Kotagal et al. [22,23]. The similarity in results might be explained through the usage of similar criteria in identifying versive and nonversive head movements. Various previous studies could not determine the lateralizing values of auras [20,22,27]. Guptka et al., however, claimed that autonomic and psychic auras are associated with a right temporal focus [28]. This study did not determine a lateralizing value for psychic auras. Autonomic auras, on the other hand, were associated with right TLE, similar to the results of Guptka et al. The result that this study reached in terms of autonomic auras was not statistically significant; however, the association of autonomic auras with right TLE indicates that similar research conducted on larger groups of patients might reach decisive results. Autonomic auras might be associated with right TLE, as the autonomic network lateralizes to the right temporal lobe [29,30]. This study indicates that olfactory auras can be associated with right TLE, which has not been suggested by the previous studies. Again, it is believed that research conducted on larger series of patients might result more definitive results.
This study indicates that ictal speech has a lateralizing value for the right temporal lobe, and this result confirms previous studies. Ictal vocalization might be associated with the left temporal lobe; however, this association has a low statistical value and, thus, is not meaningful result. In terms of vegetative symptoms such as ictal coughing, urinary urge, vomiting, and drinking, it can be stated that, similar to the results of the previous studies, these are found to be rare and, thus, do not present clinically useful lateralizing values [29]. Various studies have been conducted on periictal fear, which is an ictal emotional symptom, and it has been shown that this symptom does not have a lateralizing value [31–33]. This study, likewise, did not reach a meaningful result in terms of ictal fear, laughing, or crying. This study evaluated semiologic signs according to seizure-onset age as seizure-onset age and, thus, epilepsy duration might have an impact on pathophysiologic mechanisms and might be predictive in drug-resistant seizures. Previous research that made similar evaluations of semiologic signs according to seizure-onset age accepted 18 as the level for determining early or late age at seizure onset [19]. Other studies [34,35] have claimed the seizures of patients N6 years of age to be similar to the seizures of adults and seizure semiology of infants and children to be quite different. Similarly, Olbrich et al. [17], in their study that compared clinical lateralizing signs in infant–child and adolescent groups, found significant differences between these groups. Considering the importance of the first years in terms of seizure features as has been indicated by the previous literature, this study accepted 2 as the age level and reached the conclusion that oroalimentary automatism is statistically significantly more frequent in the patient group with seizure onset at age ≤ 2 years old (average epilepsy duration: 23.7 years) when compared to the patient group with seizure onset at age N 2 years old (average epilepsy duration: 15.43 years). This result can be explained by a more distinct hippocampal sclerosis that emerged as a result of longer epilepsy duration. In addition, the present study also found out that asymmetric tonic limb posturing, which is a complex automatism, is statistically significantly more frequent in the patient group with later seizure-onset age. This result, which is a similar one to that found by previous studies, suggests that complex automatisms can be associated with brain maturation; the more mature the brain becomes, the more that complex symptomatology emerges [17, 36]. This study did not find any other difference between different age groups and, thus, supports that view that auras and emotional and psychical symptoms are not bound to age [32]. Further studies that consider larger patient groups would certainly reveal more conclusive results. Previous studies have linked gender differences to the functional and anatomical organization of temporal structures. The results of this study indicated that emotional signs are more frequent in women than in men. Similarly, Meletti et al. have indicated that in their study, emotional responses were more frequent in women than in men [12]. In addition to this, Chiesa et al. have shown that there is a female predominance in terms of ictal fear and also concluded that this predominance of women is even more distinct in adults [5]. Studies conducted on human and animal models have shown the critical role of the amygdala in emotional stimulation memory. It has also been argued that the amygdala, in terms of its relation to emotional stimulation memory, has a gender-associated lateralizing value [13]. In addition to differences in amygdala response in men and women, the structure of the amygdala is also different in different sexes. Hormonal or sociocultural effects might also have a role in the differences of emotional expressions between male and female patients. The gradual increase in the differences of emotional expressions between sexes from childhood to adulthood also strengthens the idea that these differences occur during maturation [37]. It should also be considered that women tend to express their feelings more often than men, and this could potentially explain the difference in the frequency of ictal emotional symptoms between men and women. As an addition to
Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
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physiopathological explanations, it should be considered that adult males tend to ignore or suppress their feelings [5]. This speculative point certainly needs further research. This study included only patients with TLE with drug-resistant seizures; therefore, the results might not be representative for all TLE populations. Clinical lateralizing signs, however, can only be assessed in detail in patient groups that can be monitored by video-EEG. A similar restriction, therefore, is applicable to all studies which evaluate lateralizing signs. 5. Conclusion In conclusion, some frequently observed semiologic signs can lateralize the seizure focus at a very highly reliable rate and have important guiding values preoperatively. Further, lateralizing values differ according to gender and seizure-onset age as these might reveal crucial information about pathophysiological mechanisms. Finally, lateralizing values of rare semiologic signs are hard to determine await future studies with larger numbers of patients. Conflict of interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this paper is consistent with those guidelines. References [1] Elger CE, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy Behav 2008;12:501–5392. [2] Noachtar S, Peters AS. Semiology of epileptic seizures: a critical review. Epilepsy Behav 2009;15:2–9. [3] Loddenkemper T, Kotagal P. Lateralizing signs during seizures in focal epilepsy. Epilepsy Behav 2005;7:1–17. [4] Karataş A, Aksoy Ö, Bilir E, Erdem A. Yetişkinlerde Epilepsi Cerrahisi: Cerrahi Öncesi Değerlendirmeler ve Cerrahi Yöntemler. Nöroloji Dergisi 2004;2(2):152–60. [5] Chiesa V, Gardella E, Tassi L, Canger R, Lo Russo G, Piazzini A, et al. Age-related gender differences in reporting ictal fear: analysis of case histories and review of the literature. Epilepsia 2007;48(12):2361–4. [6] Tezer FI, Kurne A, Soylu AR, Saygi S. Effects of lateralisation and gender on temporal lobe ictal behavior associated with hippocampal sclerosis. Seizure 2004;13:418–24. [7] Santana MTCG, Jakowski AP, Britto FS, Sandim GB, Caboclo LOSF, Centeno RS, et al. Gender and hemispheric differences in temporal lobe epilepsy: a VBM study. Seizure 2014;23:274–9. [8] Toth V, Fogarasi A, Karadi K, Kovacs N, Ebner A, Jansky J. Ictal affective symptoms in temporal lobe epilepsy are related to gender and age. Epilepsia 2010;51(7): 1126–32. [9] Savic I, Engel Jr J. Sex differences in patients with mesial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998;65:910–2. [10] Janszky J, Schulz R, Janszky I, Ebner A. Medial temporal lobe epilepsy: gender differences. J Neurol Neurosurg Psychiatry 2004;75:773–5. [11] Doherty MJ, Rostad SW, Abson Kraemer DL, Vossler DG, Haltiner A. Neocortical gliosis in temporal lobe epilepsy: gender-based differences. Epilepsia 2007;48(8):1455–9. [12] Meletti S, Tassi L, Mai R, Fini N, Tassinari CA, Russo GL. Emotions induced by intracerebral electrical stimulation of the temporal lobe. Epilepsia 2006;47(5):47–51.
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Please cite this article as: Erkoç Ataoğlu E, et al, An evaluation of lateralizing signs in patients with temporal lobe epilepsy, Epilepsy Behav (2015), http://dx.doi.org/10.1016/j.yebeh.2015.04.015
