BRIEF COMMUNICATION
Clinical significance of nonhabitual seizures during intracranial EEG monitoring *†Stjepana Kovac, *Roman Rodionov, ‡Suganthi Chinnasami, ‡Tim Wehner, ‡Catherine A. Scott, *Andrew W. McEvoy, *Anna Miserocchi, and *‡Beate Diehl Epilepsia, 55(1):e1–e5, 2014 doi: 10.1111/epi.12462
SUMMARY
Dr. Stjepana Kovac has a special interest in clinical and experimental epilepsy.
This study sought to determine the frequency and clinical significance of nonhabitual seizures in 101 consecutive patients undergoing presurgical intracranial electroencephalography intracranial (icEEG) recording. We compared clinical data, recording details, and postsurgical outcome in patients with nonhabitual seizures to those without nonhabitual seizures during icEEG. In patients with nonhabitual seizures we compared icEEG recordings of nonhabitual seizures to recordings of habitual seizures. Nonhabitual seizures were recorded in 10% of patients. Those patients had a significantly higher rate of procedure-related complications compared to patients without nonhabitual seizures. Ultimate seizure outcome did not differ between the groups. Nonhabitual seizures often occurred within the first 3 days of icEEG recording and had larger seizure-onset zones compared to the patient’s habitual seizures. Nonhabitual seizures have no effect on outcome of epilepsy surgery but may serve as important markers of procedure-related complications during icEEG. KEY WORDS: Epilepsy surgery, Atypical seizures, Invasive EEG, Subdural EEG, Presurgical evaluation.
pathology that triggers nonhabitual seizures in patients who are undergoing icEEG for pharmacoresistant epilepsy. There is evidence from case reports and small case series that intracerebral or subdural/subarachnoidal hematoma may irritate the cortex, thereby triggering nonhabitual seizures.2,3 Moreover, nonhabitual seizures can present with a clinical correlate, that is, nonhabitual semiology. Although these observations suggest that nonhabitual seizures may indicate icEEG-related complications, it remains unclear whether nonhabitual seizures are seen more often in patients suffering from complications during icEEG. Finally, whether nonhabitual seizures themselves affect outcome, is uncertain. Our goal was to determine the frequency, patient characteristics, and circumstances of spontaneous nonhabitual seizures during icEEG recording for pharmacoresistant epilepsy in a large number of patients. We aimed to determine the differences between habitual and nonhabitual seizures within the same patient, and whether the occurrence of the latter affects postoperative outcome.
The occurrence of nonhabitual seizures in patients undergoing intracranial electroencephalography (icEEG) recording, defined as seizures presenting with nonhabitual semiology and/or atypical electrographic seizure pattern, is difficult to interpret. A previous study has reported “iatrogenic,” nonhabitual seizures during icEEG.1 This study screened for the occurrence of vasogenic edema on magnetic resonance imaging (MRI) brain imaging after implantation of intracranial electrodes as a precipitant of nonhabitual seizures and identified mainly electrographic nonhabitual seizures. However, edema is not the only Accepted September 30, 2013; Early View publication December 2, 2013. *Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; †Department of Neurology, University of Muenster, Muenster, Germany; and ‡Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom Address correspondence to Stjepana Kovac, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, U.K. E-mail: [email protected] Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
e1
e2 S. Kovac et al.
Methods We retrospectively reviewed telemetry reports of all patients who underwent icEEG (January 2008–March 2013) at the National Hospital for Neurology and Neurosurgery in London, United Kingdom. The cohort was divided into two groups based on the occurrence of nonhabitual seizures. Nonhabitual seizures were defined as seizures with (1) a semiology that differed from the patient’s reported seizure semiology/semiology recorded during previous scalp videoEEG telemetry. The nonhabitual nature of the clinical seizure was further confirmed with the patient and family at the time of the icEEG recording. In addition we defined seizures as electrographically nonhabitual (2) if they differed in their electrographic onset involving electrodes distant from those involved during habitual clinical or subclinical seizures as recorded during the icEEG study. EEG seizure patterns were classified as focal if their ictal-onset zone was confined to a defined continuous anatomic structure (e.g., gyrus). Seizures were classified as regional if the seizureonset zone involved two distinct anatomic structures. icEEG was recorded at 512 Hz using a 128-channel EEG machine (NicoletOne LTM-system; Viasys, Cardinal Health, NeuroCare, Madison, WI, U.S.A.). Electrode locations and distances were determined using postimplantation computerized tomography (CT) images containing intracranial electrodes coregistered to the patient’s preoperative magnetic resonance imaging (MRI). In addition, intraoperative photographs were utilized (Fig. S1E). We examined coregistered preoperative and postoperative imaging and intraoperative photographs to determine the relation of the actual resection to the ictalonset zones of habitual and nonhabitual seizures (Figs. 1 and S1).
Statistical analyses were performed with SPSS (IBM SPSS 21.0, Chicago, IL, U.S.A.). We applied Fisher’s exact test for the comparison of noncontinuous variables. t-Tests were computed to compare continuous variables. All data are presented as mean standard error, with a significance level p < 0.05.
Results A total of 101 patients underwent icEEG in the study period (41 temporal lobe epilepsy [TLE]; 60 extratemporal lobe epilepsy). Nonhabitual seizures were recorded in 10 patients (9.9%). Complications of electrode implantation occurred significantly more often in patients presenting with nonhabitual seizures compared to the group of patients where no nonhabitual seizures were recorded (p = 0.025; Fisher’s exact test; Table 1). The two groups did not differ with regard to duration of epilepsy, number of clinical/subclinical seizures recorded during icEEG, and number and types of electrodes implanted (Table S1). Of 101 patients, to date 75 have proceeded to resective surgery. Of 26 patients who did not proceed to surgery, this was due to overlap of the seizure-onset zone with eloquent cortex (10 patients), widespread/bilateral seizure-onset zones, or discordance of seizure onset with an existing lesion (13 patients), due to the patient finally denying resection (two patients) or due to the patient still awaiting surgery (one patient). Of those 75 patients who proceeded to surgery, in 57 patients a minimum of 6 months postoperative follow-up was available (range 6–61 months). There was no significant difference in the proportion of patients with seizure-free outcome (Engel class IA + B) between patients with or without nonhabitual seizures during icEEG (60% vs. 49%, p = 0.398).
Figure 1. Comparison of the ictal-onset zones for habitual and nonhabitual seizures. Coregistration of the electrode positions with the patient’s preoperative MRI (patients 1–10). Electrodes involved in the habitual seizure onset are highlighted in red; those involved in nonhabitual seizure onsets are highlighted in blue. Note that in patient 3, the electrographic seizure onset of nonhabitual and habitual seizure onsets was the same, with different ensuing propagation. Epilepsia ILAE
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
31 (F)
30 (F)
32 (F)
28 (M)
26 (M)
25 (M)
2
3
4
5
6
7
21 (F)
33 (M)
Pt. no
1
8
Age (sex)
6
12
15
6
1
15
24
20
Age at onset of epilepsy (years)
PLE/right
OLE/right
FLE/left
TLE/left
PLE/right
TLE/left
TLE/left
TLE/left
Presumed epileptogenic zone
Superior and inferior parietal lobule
Calcarine fissure/lingual gyrus
Inferior precentral gyrus
Superior parietal lobule Superior temporal gyrus
Anterior polar/ hippocampus
Superior temporal gyrus
Mesial temporal
Habitual Sz onset
Superior parietal lobule
Lateral temporal
Middle frontal gyrus
Inferior precentral gyrus, superior temporal gyrus Anterior polar/ hippocampus; fast spread to extratemporal electrodes Inferior postcentral sulcus Pericentral
Anterior temporal
Nonhabitual Sz onset
Edema, mild left foot > leg weakness
No
No
Postoperative wound infection, venous infarct
No
Left homonymous hemianopia (permanent) None
Right inferior quadrant visual field defect; speech difficulty (permanent) No
No
No
No
Visual field defect (permanent)
No
Complication Fluid collection; postoperative wound infection; removal of bone flap No
Neurologic deficit after resection (duration)
No
Right occipital FCD
Left frontal encephalomalacia
Left superior temporal gyrus abnormality
Right parietal FCD
No
No
Left amygdala lesion
MRI lesion
No
Left frontal lobe resection 2005 No
No
No
No
No
No
Previous neurosurgery
Table 1. Clinical details of patients presenting with nonhabitual seizures during icEEG
Pathology
Mild MCD type IIa
Yes
No
Yes
Gliosis
Mild MCD type IIa
No
No
Yes
No
Yes
Gliosis
FCD type IIB
Hippocampal sclerosis (atypical)
Chronic leptomeningeal inflammation
Mild end folium sclerosis
Nonhabitual SOZ resected
Continued
IV/5 (12)
IA/1 (12)
IA/1 (36)
IA/1 (48)
IB/2 (6)
IA/1 (16)
IV/5 (46)
IA/1 (12)
Outcome Engels/ outcome ILAE (follow up/ months)
e3
Nonhabitual Seizures during icEEG Monitoring
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
e4
Postoperative wound infection/ subgaleal infection Frontal FLE/right 10
18 30 (M)
9
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
F, female; M, male; TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; PLE, parietal lobe epilepsy; OLE, occipital lobe epilepsy; FCD, focal cortical dysplasia; MCD, malformation of cortical development; Sz, seizure; SOZ, seizure-onset zone. a Based on the International League Against Epilepsy (ILAE) classification 2010.
IV/5 (13) No Reactive changes No No
IV/5 (8) No No pathology No No
Facial weakness, monoparesis (temporary, fully resolved) No Extraparenchymal hematoma 17 (M)
Pt. no
0
FLE/left
Anterior inferior frontal gyrus Prefrontal
postcentral gyrus Postcentral gyrus
Age (sex)
Age at onset of epilepsy (years)
Presumed epileptogenic zone
Habitual Sz onset
Nonhabitual Sz onset
Complication
Neurologic deficit after resection (duration)
Table 1. Continued.
MRI lesion
Previous neurosurgery
Pathology
Nonhabitual SOZ resected
Outcome Engels/ outcome ILAE (follow up/ months)
S. Kovac et al. Details of the patients presenting with nonhabitual seizures are summarized in Table 1. Nonhabitual clinical seizures were seen in six patients. The ictal-onset zone of these was distinct in five patients. In one patient (patient 3), nonhabitual clinical seizures arose from the same electrode contacts as the habitual seizures. One patient (patient 4) had habitual seizures with a nonhabitual remote ictal-onset zone. In three patients, nonhabitual seizures had no clinical correlate. In 6 of the 10 patients, nonhabitual seizures occurred within the first 3 days of icEEG recording. Anticonvulsants were reduced at the time that nonhabitual seizures occurred in seven patients (Table S2). This drug reduction during icEEG was to the same degree, or less, when compared to the scalp EEG recordings in all except for two patients (patients 5 and 7; Table S4). All of these nonhabitual seizures had not been recorded during previous scalp video-EEG telemetry. In addition, nonhabitual seizures did not recur after explantation of the subdural electrodes. Electrographic seizure patterns of nonhabitual seizures were regional in seven and focal in three patients, whereas in habitual seizures regional seizure patterns were recorded in only 3 patients and focal in 7 of 10 patients (p = 0.089, Fisher’s exact test, Table S2). It was noted that nonhabitual seizures occurred in cortical locations that throughout the icEEG investigation revealed interictal epileptiform activity (spikes, often in runs) and hence form part of the patient’s irritative zone. The minimum distance between electrographic onsets of atypical versus habitual seizures ranged from 0 to 6.7 cm (mean 2.8 0.8 cm; Table S2). In most cases (7/10) nonhabitual seizures were seen in the same lobe as habitual seizures, with 3 of 10 patients showing nonhabitual and habitual seizures in the same sublobar compartment. In three patients, nonhabitual seizure onset was in a different lobe when compared to habitual seizure onset (Fig. 1 and Table S3). The seizure-onset zone of habitual seizures was resected in all 10 patients, whereas the nonhabitual seizure onset zone was resected in four patients only.
Discussion We investigated nonhabitual seizures in a large group of patients who were undergoing icEEG for pharmacoresistant temporal and extratemporal lobe epilepsy. In our cohort, the frequency of nonhabitual seizures was 10%. Previous studies with smaller patient numbers have reported atypical seizures in 2.7% and approximately 14% of recordings,3,4 and have hypothesized that procedure-related complications such as cerebral edema, subdural blood collection, or infection might contribute to nonhabitual seizures.1 Our data support this, and we show that procedure-related complications were significantly more common in patients with nonhabitual seizures compared to those without them. In 6 of 10 patients with nonhabitual seizures during icEEG, a shallow fluid collection was observed on postimplantation MRI
e5 Nonhabitual Seizures during icEEG Monitoring images, which supports the suspicion that subdural collection of fluid/blood products may irritate the cortex.3 Previous studies have pointed out that the complication rate in icEEG increases with the number of electrodes implanted and the length of recording.5,6 However, we did not observe any statistical differences between the number or types of electrodes used and length of recording between the patient groups with or without nonhabitual seizures. Moreover, in 60%, nonhabitual seizures occurred within the first 3 days of icEEG recordings. A recent study has shown that invasive recordings pick up more seizures than surface EEG recordings.7 Therefore some of the seizures, particularly the electrographic seizures in our study, might not be procedure related/iatrogenic, but may have gone unrecognized in previous scalp recordings. In addition, electrode coverage is guided by the best hypothesis about the seizure-onset zone of habitual seizures and therefore nonhabitual seizures may go unrecognized on icEEG if they start in cortical areas without icEEG electrode coverage. It has been hypothesized that anticonvulsant withdrawal may contribute to the occurrence of atypical seizures.8 Previous video-EEG telemetry in our patients with a similar degree of drug reduction did not precipitate clinical nonhabitual seizures, arguing against a role of drug reduction in precipitating nonhabitual seizures. Most nonhabitual seizures had a clinical correlate. This is in contrast to a previous study that reported electrographic nonhabitual seizures only.1 This difference may be explained by the high proportion of extratemporal cases, larger craniotomies, and possibly electrode coverage including eloquent cortex in our cohort. Habitual and nonhabitual ictal-onset zones were separated by more than 2 cm in most patients, suggesting that nonhabitual seizures do not necessarily reflect alternative spread patterns, but rather indicate a distinct zone of icEEG procedure-related “irritated” cortex. The proportion of patients with a favorable outcome after epilepsy surgery did not differ between patients with habitual seizures and patients in whom no such nonhabitual seizures were recorded during icEEG. Favorable outcomes (Engel class I) were seen in approximately 50–60% of cases and are comparable to previous studies.9–12
Conclusion The occurrence of nonhabitual seizures during icEEG should prompt the clinician to search for procedure-related complications. They are not associated with unfavorable outcome following resection.
Acknowledgments
Disclosure 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 report is consistent with those guidelines.
References 1. Khoury JA, Noe KH, Drazkowski JF, et al. Iatrogenic seizures during intracranial EEG monitoring. Epilepsia 2011;52:e123–e125. 2. Malow BA, Sato S, Kufta CV, et al. Hematoma-related seizures detected during subdural electrode monitoring. Epilepsia 1995;36:733–735. 3. Fountas KN, King DW, Jenkins PD, et al. Nonhabitual seizures in patients with implanted subdural electrodes. Stereotact Funct Neurosurg 2004;82:165–168. 4. Fountas KN, Smith JR. Subdural electrode-associated complications: a 20-year experience. Stereotact Funct Neurosurg 2007;85:264–272. 5. Hamer HM, Morris HH, Mascha EJ, et al. Complications of invasive video-EEG monitoring with subdural grid electrodes. Neurology 2002;58:97–103. 6. Arya R, Mangano FT, Horn PS, et al. Adverse events related to extraoperative invasive EEG monitoring with subdural grid electrodes: a systematic review and meta-analysis. Epilepsia 2013;54:828–839. 7. Claassen J, Perotte A, Albers D, et al. Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes. Ann Neurol 2013;74:53–64. 8. Engel J Jr, Crandall PH. Falsely localizing ictal onsets with depth EEG telemetry during anticonvulsant withdrawal. Epilepsia 1983;24:344– 355. 9. Bulacio JC, Jehi L, Wong C, et al. Long-term seizure outcome after resective surgery in patients evaluated with intracranial electrodes. Epilepsia 2012;53:1722–1730. 10. Carrette E, Vonck K, De Herdt V, et al. Predictive factors for outcome of invasive video-EEG monitoring and subsequent resective surgery in patients with refractory epilepsy. Clin Neurol Neurosurg 2010;112:118–126. 11. Van Gompel JJ, Worrell GA, Bell ML, et al. Intracranial electroencephalography with subdural grid electrodes: techniques, complications, and outcomes. Neurosurgery 2008;63:498–505. 12. Burneo JG, Villanueva V, Knowlton RC, et al. Kaplan–Meier analysis on seizure outcome after epilepsy surgery: do gender and race influence it? Seizure 2008;17:314–319.
Supporting Information Additional Supporting Information may be found in the online version of this article: Figure S1. Analysis of preresection and postresection images. Table S1. Comparison of the two patient groups: patients with nonhabitual seizures versus patients without nonhabitual seizures during icEEG. Table S2. Comparison of nonhabitual versus habitual seizures. Table S3. Electrographic comparison of nonhabitual versus habitual seizures. Table S4. Drug reduction during noninvasive/invasive video-EEG monitoring
This work was undertaken at UCLH/UCL, which receives a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres’ funding scheme. Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
Clinical significance of nonhabitual seizures during intracranial EEG monitoring *†Stjepana Kovac, *Roman Rodionov, ‡Suganthi Chinnasami, ‡Tim Wehner, ‡Catherine A. Scott, *Andrew W. McEvoy, *Anna Miserocchi, and *‡Beate Diehl Epilepsia, 55(1):e1–e5, 2014 doi: 10.1111/epi.12462
SUMMARY
Dr. Stjepana Kovac has a special interest in clinical and experimental epilepsy.
This study sought to determine the frequency and clinical significance of nonhabitual seizures in 101 consecutive patients undergoing presurgical intracranial electroencephalography intracranial (icEEG) recording. We compared clinical data, recording details, and postsurgical outcome in patients with nonhabitual seizures to those without nonhabitual seizures during icEEG. In patients with nonhabitual seizures we compared icEEG recordings of nonhabitual seizures to recordings of habitual seizures. Nonhabitual seizures were recorded in 10% of patients. Those patients had a significantly higher rate of procedure-related complications compared to patients without nonhabitual seizures. Ultimate seizure outcome did not differ between the groups. Nonhabitual seizures often occurred within the first 3 days of icEEG recording and had larger seizure-onset zones compared to the patient’s habitual seizures. Nonhabitual seizures have no effect on outcome of epilepsy surgery but may serve as important markers of procedure-related complications during icEEG. KEY WORDS: Epilepsy surgery, Atypical seizures, Invasive EEG, Subdural EEG, Presurgical evaluation.
pathology that triggers nonhabitual seizures in patients who are undergoing icEEG for pharmacoresistant epilepsy. There is evidence from case reports and small case series that intracerebral or subdural/subarachnoidal hematoma may irritate the cortex, thereby triggering nonhabitual seizures.2,3 Moreover, nonhabitual seizures can present with a clinical correlate, that is, nonhabitual semiology. Although these observations suggest that nonhabitual seizures may indicate icEEG-related complications, it remains unclear whether nonhabitual seizures are seen more often in patients suffering from complications during icEEG. Finally, whether nonhabitual seizures themselves affect outcome, is uncertain. Our goal was to determine the frequency, patient characteristics, and circumstances of spontaneous nonhabitual seizures during icEEG recording for pharmacoresistant epilepsy in a large number of patients. We aimed to determine the differences between habitual and nonhabitual seizures within the same patient, and whether the occurrence of the latter affects postoperative outcome.
The occurrence of nonhabitual seizures in patients undergoing intracranial electroencephalography (icEEG) recording, defined as seizures presenting with nonhabitual semiology and/or atypical electrographic seizure pattern, is difficult to interpret. A previous study has reported “iatrogenic,” nonhabitual seizures during icEEG.1 This study screened for the occurrence of vasogenic edema on magnetic resonance imaging (MRI) brain imaging after implantation of intracranial electrodes as a precipitant of nonhabitual seizures and identified mainly electrographic nonhabitual seizures. However, edema is not the only Accepted September 30, 2013; Early View publication December 2, 2013. *Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; †Department of Neurology, University of Muenster, Muenster, Germany; and ‡Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom Address correspondence to Stjepana Kovac, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, U.K. E-mail: [email protected] Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
e1
e2 S. Kovac et al.
Methods We retrospectively reviewed telemetry reports of all patients who underwent icEEG (January 2008–March 2013) at the National Hospital for Neurology and Neurosurgery in London, United Kingdom. The cohort was divided into two groups based on the occurrence of nonhabitual seizures. Nonhabitual seizures were defined as seizures with (1) a semiology that differed from the patient’s reported seizure semiology/semiology recorded during previous scalp videoEEG telemetry. The nonhabitual nature of the clinical seizure was further confirmed with the patient and family at the time of the icEEG recording. In addition we defined seizures as electrographically nonhabitual (2) if they differed in their electrographic onset involving electrodes distant from those involved during habitual clinical or subclinical seizures as recorded during the icEEG study. EEG seizure patterns were classified as focal if their ictal-onset zone was confined to a defined continuous anatomic structure (e.g., gyrus). Seizures were classified as regional if the seizureonset zone involved two distinct anatomic structures. icEEG was recorded at 512 Hz using a 128-channel EEG machine (NicoletOne LTM-system; Viasys, Cardinal Health, NeuroCare, Madison, WI, U.S.A.). Electrode locations and distances were determined using postimplantation computerized tomography (CT) images containing intracranial electrodes coregistered to the patient’s preoperative magnetic resonance imaging (MRI). In addition, intraoperative photographs were utilized (Fig. S1E). We examined coregistered preoperative and postoperative imaging and intraoperative photographs to determine the relation of the actual resection to the ictalonset zones of habitual and nonhabitual seizures (Figs. 1 and S1).
Statistical analyses were performed with SPSS (IBM SPSS 21.0, Chicago, IL, U.S.A.). We applied Fisher’s exact test for the comparison of noncontinuous variables. t-Tests were computed to compare continuous variables. All data are presented as mean standard error, with a significance level p < 0.05.
Results A total of 101 patients underwent icEEG in the study period (41 temporal lobe epilepsy [TLE]; 60 extratemporal lobe epilepsy). Nonhabitual seizures were recorded in 10 patients (9.9%). Complications of electrode implantation occurred significantly more often in patients presenting with nonhabitual seizures compared to the group of patients where no nonhabitual seizures were recorded (p = 0.025; Fisher’s exact test; Table 1). The two groups did not differ with regard to duration of epilepsy, number of clinical/subclinical seizures recorded during icEEG, and number and types of electrodes implanted (Table S1). Of 101 patients, to date 75 have proceeded to resective surgery. Of 26 patients who did not proceed to surgery, this was due to overlap of the seizure-onset zone with eloquent cortex (10 patients), widespread/bilateral seizure-onset zones, or discordance of seizure onset with an existing lesion (13 patients), due to the patient finally denying resection (two patients) or due to the patient still awaiting surgery (one patient). Of those 75 patients who proceeded to surgery, in 57 patients a minimum of 6 months postoperative follow-up was available (range 6–61 months). There was no significant difference in the proportion of patients with seizure-free outcome (Engel class IA + B) between patients with or without nonhabitual seizures during icEEG (60% vs. 49%, p = 0.398).
Figure 1. Comparison of the ictal-onset zones for habitual and nonhabitual seizures. Coregistration of the electrode positions with the patient’s preoperative MRI (patients 1–10). Electrodes involved in the habitual seizure onset are highlighted in red; those involved in nonhabitual seizure onsets are highlighted in blue. Note that in patient 3, the electrographic seizure onset of nonhabitual and habitual seizure onsets was the same, with different ensuing propagation. Epilepsia ILAE
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
31 (F)
30 (F)
32 (F)
28 (M)
26 (M)
25 (M)
2
3
4
5
6
7
21 (F)
33 (M)
Pt. no
1
8
Age (sex)
6
12
15
6
1
15
24
20
Age at onset of epilepsy (years)
PLE/right
OLE/right
FLE/left
TLE/left
PLE/right
TLE/left
TLE/left
TLE/left
Presumed epileptogenic zone
Superior and inferior parietal lobule
Calcarine fissure/lingual gyrus
Inferior precentral gyrus
Superior parietal lobule Superior temporal gyrus
Anterior polar/ hippocampus
Superior temporal gyrus
Mesial temporal
Habitual Sz onset
Superior parietal lobule
Lateral temporal
Middle frontal gyrus
Inferior precentral gyrus, superior temporal gyrus Anterior polar/ hippocampus; fast spread to extratemporal electrodes Inferior postcentral sulcus Pericentral
Anterior temporal
Nonhabitual Sz onset
Edema, mild left foot > leg weakness
No
No
Postoperative wound infection, venous infarct
No
Left homonymous hemianopia (permanent) None
Right inferior quadrant visual field defect; speech difficulty (permanent) No
No
No
No
Visual field defect (permanent)
No
Complication Fluid collection; postoperative wound infection; removal of bone flap No
Neurologic deficit after resection (duration)
No
Right occipital FCD
Left frontal encephalomalacia
Left superior temporal gyrus abnormality
Right parietal FCD
No
No
Left amygdala lesion
MRI lesion
No
Left frontal lobe resection 2005 No
No
No
No
No
No
Previous neurosurgery
Table 1. Clinical details of patients presenting with nonhabitual seizures during icEEG
Pathology
Mild MCD type IIa
Yes
No
Yes
Gliosis
Mild MCD type IIa
No
No
Yes
No
Yes
Gliosis
FCD type IIB
Hippocampal sclerosis (atypical)
Chronic leptomeningeal inflammation
Mild end folium sclerosis
Nonhabitual SOZ resected
Continued
IV/5 (12)
IA/1 (12)
IA/1 (36)
IA/1 (48)
IB/2 (6)
IA/1 (16)
IV/5 (46)
IA/1 (12)
Outcome Engels/ outcome ILAE (follow up/ months)
e3
Nonhabitual Seizures during icEEG Monitoring
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
e4
Postoperative wound infection/ subgaleal infection Frontal FLE/right 10
18 30 (M)
9
Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
F, female; M, male; TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; PLE, parietal lobe epilepsy; OLE, occipital lobe epilepsy; FCD, focal cortical dysplasia; MCD, malformation of cortical development; Sz, seizure; SOZ, seizure-onset zone. a Based on the International League Against Epilepsy (ILAE) classification 2010.
IV/5 (13) No Reactive changes No No
IV/5 (8) No No pathology No No
Facial weakness, monoparesis (temporary, fully resolved) No Extraparenchymal hematoma 17 (M)
Pt. no
0
FLE/left
Anterior inferior frontal gyrus Prefrontal
postcentral gyrus Postcentral gyrus
Age (sex)
Age at onset of epilepsy (years)
Presumed epileptogenic zone
Habitual Sz onset
Nonhabitual Sz onset
Complication
Neurologic deficit after resection (duration)
Table 1. Continued.
MRI lesion
Previous neurosurgery
Pathology
Nonhabitual SOZ resected
Outcome Engels/ outcome ILAE (follow up/ months)
S. Kovac et al. Details of the patients presenting with nonhabitual seizures are summarized in Table 1. Nonhabitual clinical seizures were seen in six patients. The ictal-onset zone of these was distinct in five patients. In one patient (patient 3), nonhabitual clinical seizures arose from the same electrode contacts as the habitual seizures. One patient (patient 4) had habitual seizures with a nonhabitual remote ictal-onset zone. In three patients, nonhabitual seizures had no clinical correlate. In 6 of the 10 patients, nonhabitual seizures occurred within the first 3 days of icEEG recording. Anticonvulsants were reduced at the time that nonhabitual seizures occurred in seven patients (Table S2). This drug reduction during icEEG was to the same degree, or less, when compared to the scalp EEG recordings in all except for two patients (patients 5 and 7; Table S4). All of these nonhabitual seizures had not been recorded during previous scalp video-EEG telemetry. In addition, nonhabitual seizures did not recur after explantation of the subdural electrodes. Electrographic seizure patterns of nonhabitual seizures were regional in seven and focal in three patients, whereas in habitual seizures regional seizure patterns were recorded in only 3 patients and focal in 7 of 10 patients (p = 0.089, Fisher’s exact test, Table S2). It was noted that nonhabitual seizures occurred in cortical locations that throughout the icEEG investigation revealed interictal epileptiform activity (spikes, often in runs) and hence form part of the patient’s irritative zone. The minimum distance between electrographic onsets of atypical versus habitual seizures ranged from 0 to 6.7 cm (mean 2.8 0.8 cm; Table S2). In most cases (7/10) nonhabitual seizures were seen in the same lobe as habitual seizures, with 3 of 10 patients showing nonhabitual and habitual seizures in the same sublobar compartment. In three patients, nonhabitual seizure onset was in a different lobe when compared to habitual seizure onset (Fig. 1 and Table S3). The seizure-onset zone of habitual seizures was resected in all 10 patients, whereas the nonhabitual seizure onset zone was resected in four patients only.
Discussion We investigated nonhabitual seizures in a large group of patients who were undergoing icEEG for pharmacoresistant temporal and extratemporal lobe epilepsy. In our cohort, the frequency of nonhabitual seizures was 10%. Previous studies with smaller patient numbers have reported atypical seizures in 2.7% and approximately 14% of recordings,3,4 and have hypothesized that procedure-related complications such as cerebral edema, subdural blood collection, or infection might contribute to nonhabitual seizures.1 Our data support this, and we show that procedure-related complications were significantly more common in patients with nonhabitual seizures compared to those without them. In 6 of 10 patients with nonhabitual seizures during icEEG, a shallow fluid collection was observed on postimplantation MRI
e5 Nonhabitual Seizures during icEEG Monitoring images, which supports the suspicion that subdural collection of fluid/blood products may irritate the cortex.3 Previous studies have pointed out that the complication rate in icEEG increases with the number of electrodes implanted and the length of recording.5,6 However, we did not observe any statistical differences between the number or types of electrodes used and length of recording between the patient groups with or without nonhabitual seizures. Moreover, in 60%, nonhabitual seizures occurred within the first 3 days of icEEG recordings. A recent study has shown that invasive recordings pick up more seizures than surface EEG recordings.7 Therefore some of the seizures, particularly the electrographic seizures in our study, might not be procedure related/iatrogenic, but may have gone unrecognized in previous scalp recordings. In addition, electrode coverage is guided by the best hypothesis about the seizure-onset zone of habitual seizures and therefore nonhabitual seizures may go unrecognized on icEEG if they start in cortical areas without icEEG electrode coverage. It has been hypothesized that anticonvulsant withdrawal may contribute to the occurrence of atypical seizures.8 Previous video-EEG telemetry in our patients with a similar degree of drug reduction did not precipitate clinical nonhabitual seizures, arguing against a role of drug reduction in precipitating nonhabitual seizures. Most nonhabitual seizures had a clinical correlate. This is in contrast to a previous study that reported electrographic nonhabitual seizures only.1 This difference may be explained by the high proportion of extratemporal cases, larger craniotomies, and possibly electrode coverage including eloquent cortex in our cohort. Habitual and nonhabitual ictal-onset zones were separated by more than 2 cm in most patients, suggesting that nonhabitual seizures do not necessarily reflect alternative spread patterns, but rather indicate a distinct zone of icEEG procedure-related “irritated” cortex. The proportion of patients with a favorable outcome after epilepsy surgery did not differ between patients with habitual seizures and patients in whom no such nonhabitual seizures were recorded during icEEG. Favorable outcomes (Engel class I) were seen in approximately 50–60% of cases and are comparable to previous studies.9–12
Conclusion The occurrence of nonhabitual seizures during icEEG should prompt the clinician to search for procedure-related complications. They are not associated with unfavorable outcome following resection.
Acknowledgments
Disclosure 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 report is consistent with those guidelines.
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Supporting Information Additional Supporting Information may be found in the online version of this article: Figure S1. Analysis of preresection and postresection images. Table S1. Comparison of the two patient groups: patients with nonhabitual seizures versus patients without nonhabitual seizures during icEEG. Table S2. Comparison of nonhabitual versus habitual seizures. Table S3. Electrographic comparison of nonhabitual versus habitual seizures. Table S4. Drug reduction during noninvasive/invasive video-EEG monitoring
This work was undertaken at UCLH/UCL, which receives a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres’ funding scheme. Epilepsia, 55(1):1–5, 2014 doi: 10.1111/epi.12462
