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Abnormal discharges from the temporal neocortex after selective amygdalohippocampectomy and seizure outcomes
Journal of Clinical Neuroscience 22 (2015) 1797–1801
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Abnormal discharges from the temporal neocortex after selective amygdalohippocampectomy and seizure outcomes Takehiro Uda a,b,⇑, Michiharu Morino b, Noriaki Minami b, Takahiro Matsumoto b, Tatsuya Uchida b, Takamasa Kamei b a b
Department of Neurosurgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
a r t i c l e
i n f o
Article history: Received 1 January 2015 Accepted 18 March 2015
Keywords: Electrocorticography Residual spike Mesial temporal lobe epilepsy Seizure outcomes Selective amygdalohippocampectomy
a b s t r a c t The present study examined the relationship between residual discharges from the temporal neocortex postoperatively and seizure outcomes, in mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) who were treated with selective amygdalohippocampectomy (SelAH). Abnormal discharges from the temporal neocortex are often observed and remain postoperatively. However, no recommendations have been made regarding whether additional procedures to eliminate these discharges should be performed for seizure relief. We retrospectively analyzed 28 patients with unilateral MTLE and HS, who underwent transsylvian SelAH. The mean follow-up period was 29 months (range: 16–49). In the pre- and postresection states, electrocorticography (ECoG) was recorded for the temporal base and lateral temporal cortex. The extent of resection was not influenced by the results of the preresection ECoG. Even if residual abnormal discharges were identified on the temporal neocortex, no additional procedures were undertaken to eliminate these abnormalities. The postresection spike counts were examined to determine the postresective alterations in spike count, and the frequency of residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification. The postoperative seizure-free rate was 92.9%. No significant correlations were seen between a decreasing spike count and seizure outcomes (p = 0.9259), or between the absence of residual spikes and seizure outcomes (p = 1.000). Residual spikes at the temporal neocortex do not appear to influence seizure outcomes. Only mesial temporal structures should be removed, and additional procedures to eliminate residual spikes are not required. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction In the treatment of mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), surgical removal of mesial temporal structures, including the hippocampus, is associated with a higher rate of seizure control compared with medical treatment [1]. Conventionally, to approach mesial temporal structures, the anterior part of the lateral temporal lobe is removed in a procedure called standard anterior temporal lobectomy (ATL) [2,3]. Selective removal of the hippocampus, known as a selective amygdalohippocampectomy (SelAH), aims for the preservation of the temporal neocortex, and has recently been adopted in many institutions [4–10]. With SelAH, abnormal discharges, that are observed before removing the mesial temporal structures at the basal and lateral ⇑ Corresponding author. Tel.: +81 6 6645 3846; fax: +81 6 6647 8065. E-mail address: [email protected] (T. Uda). http://dx.doi.org/10.1016/j.jocn.2015.03.063 0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.
temporal cortex, sometimes change in frequency or amplitude, and remain postoperatively. However, no recommendations have been made regarding whether additional procedures should be performed in the areas with postoperative abnormal discharges, for improved seizure relief. Additional procedures may include multiple subpial transections (MST) [11] or an additional corticectomy. We aimed to examine the relationships between residual abnormal discharges and seizure outcomes, and clarify the need for additional procedures after SelAH. 2. Methods 2.1. Patient selection Between April 2010 and March 2013, a total of 76 patients underwent SelAH for the treatment of medically intractable MTLE by a single surgeon (M.M.). All patients underwent a
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non-invasive presurgical evaluation, including MRI of the head with coronal T2-weighted and fluid attenuated inversion recovery sequences, perpendicular to the axis of the hippocampus, scalp electroencephalography (EEG) with bilateral sphenoidal electrodes, interictal N-isopropyl-p(123I)-iodoamphetamine singlephoton emission CT scan, video-EEG monitoring with sphenoidal electrodes, and neuropsychological testing. Those patients with bilateral MTLE, multilobe epilepsy, MRI-negative MTLE, MTLE associated with other lesions such as a tumor, cortical dysplasia, heterotopia, or who had undergone ATL, were excluded. All patients with a history of encephalitis were also excluded. The study was approved by the Ethics Committee of Tokyo Metropolitan Neurological Hospital. Written informed consent was obtained from each patient or their parents. 2.2. Surgery and intraoperative electrocorticography (ECoG) recording All patients underwent transsylvian SelAH [5–7,12]. A standard frontotemporal craniotomy was performed, but slightly wider exposure of the temporal lobe was necessary to permit intraoperative ECoG. After wide exposure of the Sylvian fissure, the inferior peri-insular sulcus was identified at the most inferior point of the insular gyri. Along this sulcus, the inferior horn of the lateral ventricle was opened with a 15 mm cortical incision. Care was taken to avoid injuring the uncinate fasciculus, which passes through the anterior part of the limen insula. After reaching the inferior horn of the lateral ventricle, the hippocampus could be seen to form the floor of the inferior horn. The amygdala faces the hippocampus and forms part of the roof of the inferior horn of the lateral ventricle. The inferior part of the amygdala was removed to obtain the surgical field for the following procedure. The preresection hippocampal recording and ECoG were performed at this point, using strip electrodes (Unique Medical, Tokyo, Japan) at the surface of the hippocampus, mesial temporal lobe and temporal base, and the lateral temporal cortex (Fig. 1). Typically, positive biphasic spikes were identified on the hippocampus. Except in patients who showed no abnormal discharges on the hippocampus, resection of the hippocampus and parahippocampal gyrus was performed using a standardized method. The detailed surgical procedures have been reported previously [5–7,12]. After en bloc resection of the anterior 30 mm of the hippocampus and parahippocampal gyrus, the hippocampal tail and adjacent parahippocampal gyrus were removed using a Cavitron ultrasonic surgical aspirator (Dentsply, York, PA, USA) until the lateral aspect of the
Fig. 1. The positions of the strip electrodes (Unique Medical, Tokyo, Japan) for preand postresection electroencephalography recording. In the preresection recording, strip electrodes were placed on the hippocampus (1 6 contact with 5 mm spacing; A), mesial temporal lobe and temporal base (1 4 contact with 5 mm spacing, and 1 4 contact with 10 mm spacing, respectively; B), and lateral temporal cortex (1 4 contact with 10 mm spacing; C). In the postresection recording, strip electrodes were placed on the temporal base (1 4 contact with 10 mm spacing; B), and lateral temporal cortex (1 4 contact with 10 mm spacing; C).
quadrigeminal plate could be identified. The extent of resection was not influenced by the results of the hippocampal recording and ECoG. Subsequently, a postresection ECoG was performed from the same positions, using strip electrodes at the temporal base and lateral temporal cortex (Fig. 1). Even if residual abnormal discharges were identified from the temporal base and lateral temporal cortex, no additional procedures (MST or corticectomy) were undertaken to eliminate these abnormalities. The pre- and postresection recordings were made for a minimum of 2 minutes, using a scalp reference. The sensitivity was set to 75 lV/cm, the high frequency filter was 120 Hz, and the time constant was 0.3 seconds. A 50 Hz notch filter was used when necessary. The sampling rate was 250 Hz. Antiepileptic medication was discontinued from the day before the operation. Before and during ECoG recording, sevoflurane was administrated to maintain anesthesia. The concentration of sevoflurane in expiration was kept at 2.5%. No intravenous anesthesia or opioids were used. 2.3. ECoG data processing A spike was defined as a paroxysmal, fast, transient waveform with a pointed peak and negative polarity with an amplitude at least twice as high as the background activity, and lasting less than 80 milliseconds [13]. The numbers of spikes were counted manually at all electrode contact points in sequential 60 second intervals, and averaged for each electrode. This averaged number of spikes was defined as the spike count. 2.4. Evaluation The postresection spike counts were evaluated to determine the postresective alteration of the spike count, and the frequency of the residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification [14]. According to the Engel classification, the postoperative seizure outcomes are categorized as Class Ia to IVc. The patients with Engel Class Ia (complete freedom from seizures) were regarded as postoperative seizure-negative, and those with Engel Class Ib–IVc were postoperative seizure-positive. 2.5. Postresective alteration of spike count The pre- and postresective spike counts were compared for the electrodes at the temporal base, and at the lateral temporal cortex. An increase was defined when the postresective spike count increased by more than one spike per 10 seconds (Fig. 2A). Conversely, a decrease of more than one spike per 10 seconds was considered a decrease (Fig. 2B). All other situations were defined as unchanged. To simplify the analyses, these three situations for alteration of spike count were dichotomized, with increased and unchanged states grouped together as persistent, and then compared with the decreased cases. Finally, the relationships between decreasing spike count and seizure outcomes were evaluated using a one-tailed Fisher’s exact test. 2.6. Frequency of residual spike count The postresection spike count was dichotomized. In the present study, more than two spikes per 10 seconds was defined as a positive finding of residual spikes, while less than that was defined as negative. The relationships between the absence of a residual spike count and seizure outcomes were then evaluated using a one-tailed Fisher’s exact test.
T. Uda et al. / Journal of Clinical Neuroscience 22 (2015) 1797–1801
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Fig. 2. Pre- and postresection electrocorticography recordings. In both patients (A, B), abnormal discharges were found in the hippocampus, mesial temporal lobe, temporal base, and lateral temporal cortex on preresection recording. On postresection recording, these abnormal discharges at the temporal base and lateral temporal cortex had increased in Patient A and decreased in Patient B.
The statistical analyses were conducted using JMP software (version 9.0; SAS Institute, Cary, NC, USA). p < 0.05 was considered statistically significant for all analyses.
3. Results We retrospectively analyzed 28 patients (13 male, 15 female; age range: 11–68 years) who were diagnosed with unilateral MTLE with HS. Sixteen patients underwent left sided surgery and 12 right sided. For all patients, the diagnosis of HS was confirmed with a postoperative histopathological examination. The mean follow-up period was 29 months (range: 16–49). In all patients, abnormal discharges were confirmed on the hippocampus in preresective recording. SelAH achieved postoperative freedom from seizures (Engel Class Ia) in 92.9% (26/28). Postoperative seizures were observed in two patients, both involving rare disabling seizures (Engel Class IIb). The spike counts on the pre- and postresection recordings at the temporal base and lateral temporal cortex are depicted as line graphs in Figure 3. In eight patients, the frequency of spikes decreased compared to the preresection state. In another five patients, the postresection spike count was obviously increased. In another 15, spikes remained without an apparent alteration. Residual spikes (>2 per 10 seconds) were observed in 67.9% (19/28). The spike counts of the two patients who had postoperative seizures are depicted with dotted lines in Figure 3. Neither of these two patients showed frequent spikes preoperatively, and spike counts were not increased postoperatively. Among the 26 seizure-negative patients, 19 showed persistent abnormal discharges on the postresection recording. On the other hand, in one of the two postoperative seizure-positive patients, abnormal discharges were decreased on the postresection
Fig. 3. Alterations of spike counts on postresection electrocorticography recordings at the temporal base and lateral temporal cortex, compared to preresection recordings depicted as a line graph. The dotted lines indicate the patients with postoperative seizures. These patients did not show frequent spikes on preresection recordings, and their spike counts did not increase on the postresection recordings.
recording. The relationships between the alteration in spike count and seizure outcomes are demonstrated in Table 1. No significant correlation was found between a decreasing spike count and seizure outcomes (one-tailed Fisher’s exact test, p = 0.9259).
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Table 1 The relationship between the alteration of spike count and seizure outcomes
Persistent, n Decreased, n
Seizure
Seizure+
Total
19 7
1 1
20 8
Table 2 The relationship between the presence of residual spikes and postoperative seizure outcomes
Positive residual spikes, n Negative residual spikes, n
Seizure-negative
Seizure-positive
Total
19 7
0 2
19 9
Among the 26 seizure-negative patients, 19 showed more than two residual spikes per 10 seconds on the postresection recording, and were regarded as positive for residual spikes. On the other hand, in both of the seizure-positive patients, the frequencies of residual spikes were less than two per 10 seconds, regarded as negative for residual spikes. The relationships between the presence of residual spike and seizure outcomes are demonstrated in Table 2. No significant correlation was found between the absence of residual spikes and seizure outcomes (one-tailed Fisher’s exact test, p = 1.000).
4. Discussion In surgery for MTLE with HS, the spike count at the temporal neocortex was increased or unchanged in most patients (20/28) after the removal of mesial temporal structures. No correlation was found between decreases in spike counts and seizure outcomes. In addition, residual spikes (>2 per 10 seconds) at the temporal neocortex after hippocampectomy were frequently found (19/28). No correlation was found between an absence of residual spikes and seizure outcomes. Generally, in epilepsy surgery, ECoG is often used to tailor the extent of resection, because residual spikes after focus resection are considered to correlate with worse seizure outcomes [15–23]. However, the present study implies that this does not apply to SelAH for unilateral HS, so additional corticectomy or MST to eliminate residual spikes appears unnecessary. Therefore, from our results, the role of intraoperative ECoG seems to be limited, only for confirmation of the epileptogenicity of the hippocampus. Compared with SelAH, standard ATL carries a higher risk of upper quadrantanopia on the contralateral side [24]. Furthermore, in surgery on the language-dominant side, some risk of speech impairment is seen (14.5%) because of damage to the anterior temporal language area [25]. Given such risks, SelAH seems to be the more favorable procedure for MTLE. However, no clear consensus has been reached regarding its superiority in terms of seizure control rate or neuropsychological outcomes [26–30]. ATL seems to be preferred and performed more widely as a gold standard surgery to remove mesial temporal structures because of the simplicity and safety of the procedure. However, even if no statistical confirmation of superiority between ATL and SelAH has been described for indices of seizure outcomes and neuropsychological outcomes, we believe that removing the unaffected temporal neocortex is difficult to justify. This is because the comparable results between procedures may be derived from a lack of appropriate indices that reflect the functions of the temporal neocortex. The present results suggest that ATL is not necessary to remove mesial temporal structures, and indirectly represents a reason to recommend SelAH.
Few previous reports have referred to the role of ECoG in SelAH [31,32]. The phenomenon of increased neocortical spiking after SelAH was first reported in 1993, and a possible cause was speculated to be an acute disconnection of pathways between the residual temporal neocortex and the removed mesial temporal structures [31]. In another report, the spike distributions of preresection ECoG were indicated to play some role in predicting seizure outcomes [32]. In both of those studies, the persistent postresection spikes were reported to show no correlation with seizure outcomes [32]. Our findings emphasize the roles of alterations in spike count and frequency of residual spike count, and strongly suggest the irrelevance of these indices for seizure outcomes. To confirm the chronological changes in the postoperative residual spikes, a scalp EEG was performed at 1 month, 6 months, 1 year and 2 years postoperatively in our series. In the patients with increased and residual spikes, the paroxysmal abnormal discharges had typically increased in frequency at 1 month postoperatively, and gradually decreased thereafter to almost disappear by 1–2 years postoperatively. This phenomenon also supports our claim that it is unnecessary to perform additional procedures to eliminate the residual spikes. 4.1. Limitations To date, the evaluation of intraoperative ECoG has not been standardized because the amplitude and frequency of abnormal discharges are affected by the method and blood concentration of anesthesia. However, for objective statistical evaluation, some numerical indices needed to be introduced. In the present study, under a fixed anesthesia condition, the spike and spike count were defined as described in the methods section. We also introduced the definitions of the alteration of spike count (increased, decreased and unchanged), and the frequency of spike count (positive and negative), based on our clinical experience. 5. Conclusion After SelAH for MTLE with HS, residual spikes on the temporal neocortex are frequently seen. However, in our series, these residual spikes had no influence on seizure outcomes. With the exception of those patients who have evident epileptogenic lesions on the temporal neocortex, only the mesial temporal structures should be removed, and additional procedures such as MST or corticectomy to eliminate residual spikes do not appear to be required for desirable seizure outcomes. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001;345:311–8. [2] Spencer DD. Anteromedial temporal lobectomy. In: Spencer SS, Spencer DD, Grossman R, editors. Surgery for epilepsy. Boston: Blackwell Scientific Pub; 1991. p. 129–37. [3] Falconer MA, Meyer A, Hill D, et al. Treatment of temporal-lobe epilepsy by temporal lobectomy; a survey of findings and results. Lancet 1955;268:827–35. [4] Hori T, Tabuchi S, Kurosaki M, et al. Subtemporal amygdalohippocampectomy for treating medically intractable temporal lobe epilepsy. Neurosurgery 1993;33:50–6 [discussion 56–7]. [5] Wieser HG. Selective amygdalo-hippocampectomy for temporal lobe epilepsy. Epilepsia 1988;29:S100–13. [6] Wieser HG, Yasargil MG. Selective amygdalohippocampectomy as a surgical treatment of mesiobasal limbic epilepsy. Surg Neurol 1982;17:445–57.
T. Uda et al. / Journal of Clinical Neuroscience 22 (2015) 1797–1801 [7] Yasargil MG, Teddy PJ, Roth P. Selective amygdalo-hippocampectomy. Operative anatomy and surgical technique. Adv Tech Stand Neurosurg 1985;12:93–123. [8] Park TS, Bourgeois BF, Silbergeld DL, et al. Subtemporal transparahippocampal amygdalohippocampectomy for surgical treatment of mesial temporal lobe epilepsy. Technical note. J Neurosurg 1996;85:1172–6. [9] Olivier A. Transcortical selective amygdalohippocampectomy in temporal lobe epilepsy. Can J Neurol 2000;27:S68–76 [discussion S92–6]. [10] Wheatley BM. Selective amygdalohippocampectomy: the trans-middle temporal gyrus approach. Neurosurg Focus 2008;25:E4. [11] Morrell F, Whisler WW, Bleck TP. Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy. J Neurosurg 1989;70:231–9. [12] Morino M, Ichinose T, Uda T, et al. Memory outcome following transsylvian selective amygdalohippocampectomy in 62 patients with hippocampal sclerosis. J Neurosurg 2009;110:1164–9. [13] Rosenow F, Luders HO, Dinner DS, et al. Histopathological correlates of epileptogenicity as expressed by electrocorticographic spiking and seizure frequency. Epilepsia 1998;39:850–6. [14] Engel J. Surgical treatment of the epilepsies. New York: Raven Press; 1993. [15] Fiol ME, Gates JR, Torres F, et al. The prognostic value of residual spikes in the post excision electrocorticogram after temporal lobectomy. Neurology 1991;41:512–6. [16] McBride MC, Binnie CD, Janota I, et al. Predictive value of intraoperative electrocorticograms in resective epilepsy surgery. Ann Neurol 1991;30:526–32. [17] Rasmussen T. Characteristics of a pure culture of frontal lobe epilepsy. Epilepsia 1983;24:482–93. [18] So N, Olivier A, Andermann F, et al. Results of surgical treatment in patients with bitemporal epileptiform abnormalities. Ann Neurol 1989;25:432–9. [19] Wyllie E, Luders H, Morris 3rd HH, et al. Clinical outcome after complete or partial cortical resection for intractable epilepsy. Neurology 1987;37:1634–41. [20] Wray CD, McDaniel SS, Saneto RP, et al. Is postresective intraoperative electrocorticography predictive of seizure outcomes in children? J Neurosurg Pediatr 2012;9:546–51. [21] Gelinas JN, Battison AW, Smith S, et al. Electrocorticography and seizure outcomes in children with lesional epilepsy. Childs Nerv Syst 2011;27:381–90.
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[22] Tripathi M, Garg A, Gaikwad S, et al. Intra-operative electrocorticography in lesional epilepsy. Epilepsy Res 2010;89:133–41. [23] Kanner AM, Kaydanova Y, deToledo-Morrell L, et al. Tailored anterior temporal lobectomy. Relation between extent of resection of mesial structures and postsurgical seizure outcome. Arch Neurol 1995;52:173–8. [24] Mengesha T, Abu-Ata M, Haas KF, et al. Visual field defects after selective amygdalohippocampectomy and standard temporal lobectomy. J Neuroophthalmol 2009;29:208–13. [25] Schwartz TH, Devinsky O, Doyle W, et al. Preoperative predictors of anterior temporal language areas. J Neurosurg 1998;89:962–70. [26] Hu WH, Zhang C, Zhang K, et al. Selective amygdalohippocampectomy versus anterior temporal lobectomy in the management of mesial temporal lobe epilepsy: a meta-analysis of comparative studies. J Neurosurg 2013;119:1089–97. [27] Josephson CB, Dykeman J, Fiest KM, et al. Systematic review and meta-analysis of standard vs selective temporal lobe epilepsy surgery. Neurology 2013;80:1669–76. [28] Bujarski KA, Hirashima F, Roberts DW, et al. Long-term seizure, cognitive, and psychiatric outcome following trans-middle temporal gyrus amygdalohippocampectomy and standard temporal lobectomy. J Neurosurg 2013;119:16–23. [29] Kuang Y, Yang T, Gu J, et al. Comparison of therapeutic effects between selective amygdalohippocampectomy and anterior temporal lobectomy for the treatment of temporal lobe epilepsy: a meta-analysis. Br J Neurosurg 2014;28:374–7. [30] Morino M, Uda T, Naito K, et al. Comparison of neuropsychological outcomes after selective amygdalohippocampectomy versus anterior temporal lobectomy. Epilepsy Behav 2006;9:95–100. [31] Cendes F, Dubeau F, Olivier A, et al. Increased neocortical spiking and surgical outcome after selective amygdalo-hippocampectomy. Epilepsy Res 1993;16:195–206. [32] Chen X, Sure U, Haag A, et al. Predictive value of electrocorticography in epilepsy patients with unilateral hippocampal sclerosis undergoing selective amygdalohippocampectomy. Neurosurg Rev 2006;29:108–13.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Abnormal discharges from the temporal neocortex after selective amygdalohippocampectomy and seizure outcomes Takehiro Uda a,b,⇑, Michiharu Morino b, Noriaki Minami b, Takahiro Matsumoto b, Tatsuya Uchida b, Takamasa Kamei b a b
Department of Neurosurgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
a r t i c l e
i n f o
Article history: Received 1 January 2015 Accepted 18 March 2015
Keywords: Electrocorticography Residual spike Mesial temporal lobe epilepsy Seizure outcomes Selective amygdalohippocampectomy
a b s t r a c t The present study examined the relationship between residual discharges from the temporal neocortex postoperatively and seizure outcomes, in mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) who were treated with selective amygdalohippocampectomy (SelAH). Abnormal discharges from the temporal neocortex are often observed and remain postoperatively. However, no recommendations have been made regarding whether additional procedures to eliminate these discharges should be performed for seizure relief. We retrospectively analyzed 28 patients with unilateral MTLE and HS, who underwent transsylvian SelAH. The mean follow-up period was 29 months (range: 16–49). In the pre- and postresection states, electrocorticography (ECoG) was recorded for the temporal base and lateral temporal cortex. The extent of resection was not influenced by the results of the preresection ECoG. Even if residual abnormal discharges were identified on the temporal neocortex, no additional procedures were undertaken to eliminate these abnormalities. The postresection spike counts were examined to determine the postresective alterations in spike count, and the frequency of residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification. The postoperative seizure-free rate was 92.9%. No significant correlations were seen between a decreasing spike count and seizure outcomes (p = 0.9259), or between the absence of residual spikes and seizure outcomes (p = 1.000). Residual spikes at the temporal neocortex do not appear to influence seizure outcomes. Only mesial temporal structures should be removed, and additional procedures to eliminate residual spikes are not required. Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction In the treatment of mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), surgical removal of mesial temporal structures, including the hippocampus, is associated with a higher rate of seizure control compared with medical treatment [1]. Conventionally, to approach mesial temporal structures, the anterior part of the lateral temporal lobe is removed in a procedure called standard anterior temporal lobectomy (ATL) [2,3]. Selective removal of the hippocampus, known as a selective amygdalohippocampectomy (SelAH), aims for the preservation of the temporal neocortex, and has recently been adopted in many institutions [4–10]. With SelAH, abnormal discharges, that are observed before removing the mesial temporal structures at the basal and lateral ⇑ Corresponding author. Tel.: +81 6 6645 3846; fax: +81 6 6647 8065. E-mail address: [email protected] (T. Uda). http://dx.doi.org/10.1016/j.jocn.2015.03.063 0967-5868/Ó 2015 Elsevier Ltd. All rights reserved.
temporal cortex, sometimes change in frequency or amplitude, and remain postoperatively. However, no recommendations have been made regarding whether additional procedures should be performed in the areas with postoperative abnormal discharges, for improved seizure relief. Additional procedures may include multiple subpial transections (MST) [11] or an additional corticectomy. We aimed to examine the relationships between residual abnormal discharges and seizure outcomes, and clarify the need for additional procedures after SelAH. 2. Methods 2.1. Patient selection Between April 2010 and March 2013, a total of 76 patients underwent SelAH for the treatment of medically intractable MTLE by a single surgeon (M.M.). All patients underwent a
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non-invasive presurgical evaluation, including MRI of the head with coronal T2-weighted and fluid attenuated inversion recovery sequences, perpendicular to the axis of the hippocampus, scalp electroencephalography (EEG) with bilateral sphenoidal electrodes, interictal N-isopropyl-p(123I)-iodoamphetamine singlephoton emission CT scan, video-EEG monitoring with sphenoidal electrodes, and neuropsychological testing. Those patients with bilateral MTLE, multilobe epilepsy, MRI-negative MTLE, MTLE associated with other lesions such as a tumor, cortical dysplasia, heterotopia, or who had undergone ATL, were excluded. All patients with a history of encephalitis were also excluded. The study was approved by the Ethics Committee of Tokyo Metropolitan Neurological Hospital. Written informed consent was obtained from each patient or their parents. 2.2. Surgery and intraoperative electrocorticography (ECoG) recording All patients underwent transsylvian SelAH [5–7,12]. A standard frontotemporal craniotomy was performed, but slightly wider exposure of the temporal lobe was necessary to permit intraoperative ECoG. After wide exposure of the Sylvian fissure, the inferior peri-insular sulcus was identified at the most inferior point of the insular gyri. Along this sulcus, the inferior horn of the lateral ventricle was opened with a 15 mm cortical incision. Care was taken to avoid injuring the uncinate fasciculus, which passes through the anterior part of the limen insula. After reaching the inferior horn of the lateral ventricle, the hippocampus could be seen to form the floor of the inferior horn. The amygdala faces the hippocampus and forms part of the roof of the inferior horn of the lateral ventricle. The inferior part of the amygdala was removed to obtain the surgical field for the following procedure. The preresection hippocampal recording and ECoG were performed at this point, using strip electrodes (Unique Medical, Tokyo, Japan) at the surface of the hippocampus, mesial temporal lobe and temporal base, and the lateral temporal cortex (Fig. 1). Typically, positive biphasic spikes were identified on the hippocampus. Except in patients who showed no abnormal discharges on the hippocampus, resection of the hippocampus and parahippocampal gyrus was performed using a standardized method. The detailed surgical procedures have been reported previously [5–7,12]. After en bloc resection of the anterior 30 mm of the hippocampus and parahippocampal gyrus, the hippocampal tail and adjacent parahippocampal gyrus were removed using a Cavitron ultrasonic surgical aspirator (Dentsply, York, PA, USA) until the lateral aspect of the
Fig. 1. The positions of the strip electrodes (Unique Medical, Tokyo, Japan) for preand postresection electroencephalography recording. In the preresection recording, strip electrodes were placed on the hippocampus (1 6 contact with 5 mm spacing; A), mesial temporal lobe and temporal base (1 4 contact with 5 mm spacing, and 1 4 contact with 10 mm spacing, respectively; B), and lateral temporal cortex (1 4 contact with 10 mm spacing; C). In the postresection recording, strip electrodes were placed on the temporal base (1 4 contact with 10 mm spacing; B), and lateral temporal cortex (1 4 contact with 10 mm spacing; C).
quadrigeminal plate could be identified. The extent of resection was not influenced by the results of the hippocampal recording and ECoG. Subsequently, a postresection ECoG was performed from the same positions, using strip electrodes at the temporal base and lateral temporal cortex (Fig. 1). Even if residual abnormal discharges were identified from the temporal base and lateral temporal cortex, no additional procedures (MST or corticectomy) were undertaken to eliminate these abnormalities. The pre- and postresection recordings were made for a minimum of 2 minutes, using a scalp reference. The sensitivity was set to 75 lV/cm, the high frequency filter was 120 Hz, and the time constant was 0.3 seconds. A 50 Hz notch filter was used when necessary. The sampling rate was 250 Hz. Antiepileptic medication was discontinued from the day before the operation. Before and during ECoG recording, sevoflurane was administrated to maintain anesthesia. The concentration of sevoflurane in expiration was kept at 2.5%. No intravenous anesthesia or opioids were used. 2.3. ECoG data processing A spike was defined as a paroxysmal, fast, transient waveform with a pointed peak and negative polarity with an amplitude at least twice as high as the background activity, and lasting less than 80 milliseconds [13]. The numbers of spikes were counted manually at all electrode contact points in sequential 60 second intervals, and averaged for each electrode. This averaged number of spikes was defined as the spike count. 2.4. Evaluation The postresection spike counts were evaluated to determine the postresective alteration of the spike count, and the frequency of the residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification [14]. According to the Engel classification, the postoperative seizure outcomes are categorized as Class Ia to IVc. The patients with Engel Class Ia (complete freedom from seizures) were regarded as postoperative seizure-negative, and those with Engel Class Ib–IVc were postoperative seizure-positive. 2.5. Postresective alteration of spike count The pre- and postresective spike counts were compared for the electrodes at the temporal base, and at the lateral temporal cortex. An increase was defined when the postresective spike count increased by more than one spike per 10 seconds (Fig. 2A). Conversely, a decrease of more than one spike per 10 seconds was considered a decrease (Fig. 2B). All other situations were defined as unchanged. To simplify the analyses, these three situations for alteration of spike count were dichotomized, with increased and unchanged states grouped together as persistent, and then compared with the decreased cases. Finally, the relationships between decreasing spike count and seizure outcomes were evaluated using a one-tailed Fisher’s exact test. 2.6. Frequency of residual spike count The postresection spike count was dichotomized. In the present study, more than two spikes per 10 seconds was defined as a positive finding of residual spikes, while less than that was defined as negative. The relationships between the absence of a residual spike count and seizure outcomes were then evaluated using a one-tailed Fisher’s exact test.
T. Uda et al. / Journal of Clinical Neuroscience 22 (2015) 1797–1801
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Fig. 2. Pre- and postresection electrocorticography recordings. In both patients (A, B), abnormal discharges were found in the hippocampus, mesial temporal lobe, temporal base, and lateral temporal cortex on preresection recording. On postresection recording, these abnormal discharges at the temporal base and lateral temporal cortex had increased in Patient A and decreased in Patient B.
The statistical analyses were conducted using JMP software (version 9.0; SAS Institute, Cary, NC, USA). p < 0.05 was considered statistically significant for all analyses.
3. Results We retrospectively analyzed 28 patients (13 male, 15 female; age range: 11–68 years) who were diagnosed with unilateral MTLE with HS. Sixteen patients underwent left sided surgery and 12 right sided. For all patients, the diagnosis of HS was confirmed with a postoperative histopathological examination. The mean follow-up period was 29 months (range: 16–49). In all patients, abnormal discharges were confirmed on the hippocampus in preresective recording. SelAH achieved postoperative freedom from seizures (Engel Class Ia) in 92.9% (26/28). Postoperative seizures were observed in two patients, both involving rare disabling seizures (Engel Class IIb). The spike counts on the pre- and postresection recordings at the temporal base and lateral temporal cortex are depicted as line graphs in Figure 3. In eight patients, the frequency of spikes decreased compared to the preresection state. In another five patients, the postresection spike count was obviously increased. In another 15, spikes remained without an apparent alteration. Residual spikes (>2 per 10 seconds) were observed in 67.9% (19/28). The spike counts of the two patients who had postoperative seizures are depicted with dotted lines in Figure 3. Neither of these two patients showed frequent spikes preoperatively, and spike counts were not increased postoperatively. Among the 26 seizure-negative patients, 19 showed persistent abnormal discharges on the postresection recording. On the other hand, in one of the two postoperative seizure-positive patients, abnormal discharges were decreased on the postresection
Fig. 3. Alterations of spike counts on postresection electrocorticography recordings at the temporal base and lateral temporal cortex, compared to preresection recordings depicted as a line graph. The dotted lines indicate the patients with postoperative seizures. These patients did not show frequent spikes on preresection recordings, and their spike counts did not increase on the postresection recordings.
recording. The relationships between the alteration in spike count and seizure outcomes are demonstrated in Table 1. No significant correlation was found between a decreasing spike count and seizure outcomes (one-tailed Fisher’s exact test, p = 0.9259).
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T. Uda et al. / Journal of Clinical Neuroscience 22 (2015) 1797–1801
Table 1 The relationship between the alteration of spike count and seizure outcomes
Persistent, n Decreased, n
Seizure
Seizure+
Total
19 7
1 1
20 8
Table 2 The relationship between the presence of residual spikes and postoperative seizure outcomes
Positive residual spikes, n Negative residual spikes, n
Seizure-negative
Seizure-positive
Total
19 7
0 2
19 9
Among the 26 seizure-negative patients, 19 showed more than two residual spikes per 10 seconds on the postresection recording, and were regarded as positive for residual spikes. On the other hand, in both of the seizure-positive patients, the frequencies of residual spikes were less than two per 10 seconds, regarded as negative for residual spikes. The relationships between the presence of residual spike and seizure outcomes are demonstrated in Table 2. No significant correlation was found between the absence of residual spikes and seizure outcomes (one-tailed Fisher’s exact test, p = 1.000).
4. Discussion In surgery for MTLE with HS, the spike count at the temporal neocortex was increased or unchanged in most patients (20/28) after the removal of mesial temporal structures. No correlation was found between decreases in spike counts and seizure outcomes. In addition, residual spikes (>2 per 10 seconds) at the temporal neocortex after hippocampectomy were frequently found (19/28). No correlation was found between an absence of residual spikes and seizure outcomes. Generally, in epilepsy surgery, ECoG is often used to tailor the extent of resection, because residual spikes after focus resection are considered to correlate with worse seizure outcomes [15–23]. However, the present study implies that this does not apply to SelAH for unilateral HS, so additional corticectomy or MST to eliminate residual spikes appears unnecessary. Therefore, from our results, the role of intraoperative ECoG seems to be limited, only for confirmation of the epileptogenicity of the hippocampus. Compared with SelAH, standard ATL carries a higher risk of upper quadrantanopia on the contralateral side [24]. Furthermore, in surgery on the language-dominant side, some risk of speech impairment is seen (14.5%) because of damage to the anterior temporal language area [25]. Given such risks, SelAH seems to be the more favorable procedure for MTLE. However, no clear consensus has been reached regarding its superiority in terms of seizure control rate or neuropsychological outcomes [26–30]. ATL seems to be preferred and performed more widely as a gold standard surgery to remove mesial temporal structures because of the simplicity and safety of the procedure. However, even if no statistical confirmation of superiority between ATL and SelAH has been described for indices of seizure outcomes and neuropsychological outcomes, we believe that removing the unaffected temporal neocortex is difficult to justify. This is because the comparable results between procedures may be derived from a lack of appropriate indices that reflect the functions of the temporal neocortex. The present results suggest that ATL is not necessary to remove mesial temporal structures, and indirectly represents a reason to recommend SelAH.
Few previous reports have referred to the role of ECoG in SelAH [31,32]. The phenomenon of increased neocortical spiking after SelAH was first reported in 1993, and a possible cause was speculated to be an acute disconnection of pathways between the residual temporal neocortex and the removed mesial temporal structures [31]. In another report, the spike distributions of preresection ECoG were indicated to play some role in predicting seizure outcomes [32]. In both of those studies, the persistent postresection spikes were reported to show no correlation with seizure outcomes [32]. Our findings emphasize the roles of alterations in spike count and frequency of residual spike count, and strongly suggest the irrelevance of these indices for seizure outcomes. To confirm the chronological changes in the postoperative residual spikes, a scalp EEG was performed at 1 month, 6 months, 1 year and 2 years postoperatively in our series. In the patients with increased and residual spikes, the paroxysmal abnormal discharges had typically increased in frequency at 1 month postoperatively, and gradually decreased thereafter to almost disappear by 1–2 years postoperatively. This phenomenon also supports our claim that it is unnecessary to perform additional procedures to eliminate the residual spikes. 4.1. Limitations To date, the evaluation of intraoperative ECoG has not been standardized because the amplitude and frequency of abnormal discharges are affected by the method and blood concentration of anesthesia. However, for objective statistical evaluation, some numerical indices needed to be introduced. In the present study, under a fixed anesthesia condition, the spike and spike count were defined as described in the methods section. We also introduced the definitions of the alteration of spike count (increased, decreased and unchanged), and the frequency of spike count (positive and negative), based on our clinical experience. 5. Conclusion After SelAH for MTLE with HS, residual spikes on the temporal neocortex are frequently seen. However, in our series, these residual spikes had no influence on seizure outcomes. With the exception of those patients who have evident epileptogenic lesions on the temporal neocortex, only the mesial temporal structures should be removed, and additional procedures such as MST or corticectomy to eliminate residual spikes do not appear to be required for desirable seizure outcomes. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References [1] Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001;345:311–8. [2] Spencer DD. Anteromedial temporal lobectomy. In: Spencer SS, Spencer DD, Grossman R, editors. Surgery for epilepsy. Boston: Blackwell Scientific Pub; 1991. p. 129–37. [3] Falconer MA, Meyer A, Hill D, et al. Treatment of temporal-lobe epilepsy by temporal lobectomy; a survey of findings and results. Lancet 1955;268:827–35. [4] Hori T, Tabuchi S, Kurosaki M, et al. Subtemporal amygdalohippocampectomy for treating medically intractable temporal lobe epilepsy. Neurosurgery 1993;33:50–6 [discussion 56–7]. [5] Wieser HG. Selective amygdalo-hippocampectomy for temporal lobe epilepsy. Epilepsia 1988;29:S100–13. [6] Wieser HG, Yasargil MG. Selective amygdalohippocampectomy as a surgical treatment of mesiobasal limbic epilepsy. Surg Neurol 1982;17:445–57.
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