- Email: [email protected]
Efficacy of Vagal Nerve Stimulation for Pharmacoresistant Poststroke Epilepsy
Journal Pre-proof Efficacy of vagal nerve stimulation for pharmacoresistant poststroke epilepsy Yuichi Kubota, Hidetoshi Nakamoto, Satoru Miyao, Takakazu Kawamata PII:
S1878-8750(19)32479-9
DOI:
https://doi.org/10.1016/j.wneu.2019.09.049
Reference:
WNEU 13348
To appear in:
World Neurosurgery
Received Date: 28 July 2019 Revised Date:
8 September 2019
Accepted Date: 9 September 2019
Please cite this article as: Kubota Y, Nakamoto H, Miyao S, Kawamata T, Efficacy of vagal nerve stimulation for pharmacoresistant poststroke epilepsy, World Neurosurgery (2019), doi: https:// doi.org/10.1016/j.wneu.2019.09.049. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
Efficacy of vagal nerve stimulation for pharmacoresistant poststroke epilepsy
Yuichi Kubotaa,b *, Hidetoshi Nakamotoa,b, Satoru Miyaoa,b, Takakazu Kawamatab a
Department of Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical Center,
Saitama, Japan b
Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan
*
Corresponding author:
Yuichi Kubota Department of Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical Center 1-1340 Mizonuma, Asaka, Saitama Phone: +81-48-466-2055 Fax: +81-48-466-2059 Email: [email protected]
Highest academic degrees for all authors Yuichi Kubota, M.D., D.Med.Sci : [email protected]
Hidetoshi Nakamoto, M.D. : [email protected] Satoru Miyao, M.D. : [email protected] Takakazu Kawamata, M.D., Ph.D. : [email protected] Keywords: antiepileptic drugs; poststroke epilepsy; seizure; vagal nerve stimulation
Short title: VNS for poststroke epilepsy
Kubota
Abstract Background: Vagal nerve stimulation (VNS) is an alternative palliative therapy for pharmacoresistant epilepsy. It has been reported to be effective for both focal and generalized epilepsy; however, most of the relevant studies have involved children or young patients. Some patients develop intractable epilepsy after stroke, despite taking antiepileptic drugs (AEDs). In this study, we investigated the efficacy of VNS for pharmacoresistant poststroke epilepsy (PPSE). Methods: We retrospectively studied 10 patients who underwent vagal nerve stimulator implantation for poststroke epilepsy after the seizures had proved refractory to appropriate AEDs. The seizure outcome was evaluated using the McHugh classification 2 years after the implantation. Results: In total, 4 (40%) patients remained seizure-free throughout the 2-year duration. In addition, seizures were reduced by >50% after 2 years in 6(60%) patients. McHugh classification was Class I for 5 patients and Class II for 5 patients. Neither intraoperative complications nor postoperative adverse effects were reported. The average intensity of VNS was 1.75 mA. Conclusions: In this small study, VNS proved to be a safe and effective therapy for PPSE. Patients with poststroke epilepsy experience physical or mental decline; therefore, it is important to control seizures in them to avoid deterioration in their quality of daily life. 1
Kubota
Introduction The development of tissue plasminogen activators and endovascular thrombectomy has drastically reduced mobility problems and mortality following ischemic stroke.1,2 Furthermore, advancements in microsurgical techniques and endovascular coiling for subarachnoid hemorrhage have improved patient outcomes. However, the number of stroke survivors has been increasing every year, and these patients can experience various poststroke complications, such as hemiparesis, aphasia, depression, and epilepsy. Epilepsy is often observed after a stroke, with a prevalence of 2%–10%.3,4 In most patients with poststroke epilepsy, the seizures can be well controlled with suitable antiepileptic drugs (AEDs). However, some patients experience uncontrolled seizures despite taking AEDs. Such pharmacoresistant poststroke epilepsy (PPSE) is relatively rare, but it can pose problems to the patients in their daily lives. Following a stroke, many patients become functionally or socially disabled; therefore, a seizure may require them to be readmitted to hospitals and to undergo long-term rehabilitation. Vagal nerve stimulation (VNS) is a therapeutic option for both generalized and focal epilepsy. It can reduce seizures without craniotomy and is being increasingly widely used.5,6 Unlike medical treatments, VNS does not cause sleepiness or dizziness; thus, it is safe for patients with poststroke epilepsy. In this study, we aimed to examine the efficacy and safety of VNS for patients with PPSE. 2
Kubota
Materials and Methods Patients In this retrospective study, we reviewed data for patients with poststroke epilepsy who attended our stroke and epilepsy center between April 2012 and March 2018 and identified consecutive patients with PPSE, defined as uncontrolled seizures despite taking at least two appropriate AEDs for more than 1 year. All the patients had undergone phase I study including magnetic resonance imaging (MRI) and video electroencephalography monitoring; however, none of them were eligible for surgical resection because the epileptogenic zone in them was located in eloquent areas. Seizure semiology in all patients was either focal onset type, such as a hemiconvulsion, or a secondary generalized type.
Procedure and analysis Vagal nerve stimulator implantation was performed under general anesthesia after obtaining patients’ written informed consent. The VNS generator was implanted in the left upper chest. Two electrodes were attached to the left vagus nerve; the electrodes were connected to an implantable pulse generator. The VNS device used in all patients was model 104 generator (RivaNova Inc., Houston, Tx, U.S.A). The devices were implanted by appropriately trained neurosurgeons. From 2 weeks after the implantation, the patients were administered an 3
Kubota
electrical current that was increased from 0.25 mA to a level that proved adequate for controlling the patients’ seizures (maximum 2.0 mA). The other parameters were same for all the patients: pulse width, 0.5 µs; signal frequency, 30 Hz; signal on time, 30 s; and signal off time, 5 min. Postoperative follow-up period was a minimum of 2 years to a maximum of 7 years. The average follow-up period was 4 years. Seizure outcomes 2 years after the implantation were compared with the rate of seizures before implantation using the Engel and McHugh classifications, which are commonly used for evaluating seizure outcomes.7
Results Table 1 summarizes the characteristics of the 10 patients and the outcomes following the vagal nerve stimulator implantation. The age ranged from 23 to 72, with an average of 64.5. There were 5 cases of cerebral hemorrhage, 3 cases of subarachnoid hemorrhage and 1 case of cerebral infarction. In total, 4 (40%) patients remained seizure-free over the 2 years, and >50% reduction in seizure frequency was observed after 2 years in 6 (60%) patients. McHugh classification was Class I for 5 patients and Class II for 5 patients. The average intensity of VNS was 1.75 mA (1.25–2.0 mA). There were no intraoperative complications, and none of the patients dropped out during the follow-up period. Among the 10 patients magnets were used by 7 patients or by their caregivers to activate the stimulator and abort a seizure at a time that they had the impression that a seizure was developing. 4
Kubota
No.
Sex
1
F
2
Age at VNS
Duration from stroke onset to
Stroke type
Involved region
70
SAH
Left Temporal
7
F
68
ICH
Right Frontal
5
3
F
70
CI
Left Frontal
6
4
M
64
ICH
Left Frontal
1
5
F
71
SAH
Left Temporal
10
6
F
62
SAH
Left Frontal
8
7
M
65
ICH
Right Parietal
77
8
M
23
ICH
Left Parietal
0
9
M
80
ICH
Left Temporal
36
10
M
72
SAH
Right Temporal
7
implantation
seizure onset (months)
Abbreviations: AEDs, antiepileptic drugs; CBZ, carbamazepine; CI, cerebral infarction; ICH, intracerebral he
Discussion This study was the first to report the seizure outcomes of VNS for patients with PPSE over 2 years. VNS was found to be extremely effective for these patients. Seizures in all the patients were well controlled by VNS, despite not being controlled by several adequate AEDs. In addition, some patients remained completely seizure-free. The reason for VNS being effective in patients with PPSE is that these patients had a relatively shorter seizure duration; the duration from epilepsy onset to vagal nerve stimulator implantation was on average 70 months, which is extremely short compared with the period 5
Kubota
of onset of refractory epilepsy in cases with childhood-onset epilepsy. The development of poststroke epilepsy reported requires several months to years.8 Therefore, there is a possibility that strong epileptogenesis seems to be difficult to be formed. In addition, VNS is advantageous for patients with PPSE because poststroke epilepsy has a focal onset and may be associated with aura; thus, patients are able to control seizures by themselves using a magnet. In fact, in 7 of the 10 patients in this study, magnets were sometimes used by the patients themselves or by their caregivers at the time of seizure onset or after the appearance of a sign of seizure. Morri et al. also reported that approximately half of the patients who used the magnet gained some benefit.9 Usually seizures in most of the patients with poststroke epilepsy are controlled with adequate AEDs such as carbamazepine, levetiracetam, and lacosamide, but some patients progress to a refractory condition. Such patients with PPSE sometimes inevitably take a high amount of AEDs to control their seizure. Nonetheless, they may suffer a seizure and are forced to get hospitalized urgently. Long-term hospitalization or transfer to a rehabilitation hospital may be necessary in such patients due to physical condition decline. Thus, in patients with PPSE, VNS therapy can be effectively used without any adverse effects unlike that with AEDs. The limitations of this study were the small number of patients and its non-prospective nature. Further research is needed to better understand the therapeutic role of VNS in patients with PPSE. In addition, this study cannot describe the relationship between seizure reduction and 6
Kubota
stroke types or regions, and further accumulation of cases should be needed. And currently, VNS is not compatible with MRI; this can be problematic if MRI is needed, as some poststroke patients occasionally need to undergo MRI for the diagnosis of ischemic stroke.
Conclusions VNS offers a potentially safe and effective treatment option for patients with PPSE. If seizures are not controlled using AEDs, introduction of VNS should be considered at an early stage from a physical and economic point of view.
Acknowledgements We gratefully appreciated Miss Yuina Nishimura for her assistance. Declarations of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
7
Kubota
References 1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 14;333(24):1581-7. 2. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al., Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 11;372(24):2285-95. 3. Roivainen R, Haapaniemi E, Putaala J, Kaste M, Tatlisumak T. Young adult ischemic stroke related acute symptomatic and late seizures: risk factors. Eur J Neurol. 2013;20:1247-55. 4. Graham NS, Crichton S, Koutroumanidis M, Wolfe CD, Rudd AG. Incidence and associations of poststroke epilepsy: the prospective South London Stroke Register. Stroke. 2013;44:605-11. 5. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia 1998;39:677–86. 6. Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol;2002:1:477–82. 7. McHugh JC, Singh HW, Phillips J, Murphy K, Doherty CP, Delanty N: Outcome measurement after vagal nerve stimulation therapy: proposal of a new classification. Epilepsia. 2007;48:375-8. 8
Kubota
8. Pitkänen A, Roivainen R, Lukasiuk K. Development of epilepsy after ischaemic stroke. Lancet Neurol. 2016;15(2):185-197. 9. Morris GL 3rd. A retrospective analysis of the effects of magnet‐ activated stimulation in conjunction with vagus nerve stimulation therapy. Epilepsy Behav 2003;4:74
9
Kubota
10
No. Sex
Age at VNS implantation
Stroke type
Involved region
Duration from stroke onset to seizure onset (months)
Duration from seizure onset to implantation (months)
Current AEDs
Preoperative seizure frequency
VNS intensity (mA)
Postoperative follow-up periods (year)
Postoperative Engel classifica McHugh seizure tion classification frequency
7
Yearly
IIB
Magnet use
1
F
70
SAH
Left Temporal
7
109
LEV3000, LTG400, CBZ300
Monthly
2.00
II
Yes
2
F
68
ICH
Right Frontal
5
30
VPA400, ZNS200, PB60
Monthly
2.00
6
Yearly
3
F
70
CI
Left Frontal
6
15
VPA400, LEV10000
Monthly
1.50
6
None
IB
I
Yes
IA
I
4
M
64
ICH
Left Frontal
1
29
LEV1000, CBZ400
Monthly
1.50
5
None
IA
No
I
Yes
5
F
71
SAH
Left Temporal
10
51
LEV3000, CBZ200, LTG200
Monthly
2.00
4
Yearly
IIB
II
Yes
6
F
62
SAH
Left Frontal
8
30
LEV3000, ZNS200, PHT200
Monthly
1.75
4
Monthly
IIIA
II
Yes
7
M
65
ICH
Right Parietal
77
92
LEV3000, CBZ400
Monthly
2.00
2
Monthly
IIIA
II
Yes
8
M
23
ICH
Left Parietal
0
61
LEV3000, CBZ700
Monthly
1.25
2
None
IB
I
Yes
9
M
80
ICH
Left Temporal
36
268
LCM100, LEV3000
Monthly
1.50
2
None
IA
I
No
10
M
72
SAH
Right Temporal
7
14
LCM400, GBP1200
Monthly
2.00
2
Yearly
IIA
II
No
Abbreviations: AEDs, antiepileptic drugs; CBZ, carbamazepine; CI, cerebral infarction; ICH, intracerebral hemorrhage; LCM, lacosamide; LEV, levetiracetam; LTG, lamotrigine; PB, phenobarbital; PHT, phenytoin; SAH, subarachnoid hemorrhage; VPA, valproate; VNS, vagal nerve stimulation; ZNS, zonisamide Monthly’ : 2-12 seizures per year. ‘Yearly’ : 0-1 seizure per year
n; ZNS, zonisamide
Abbreviations list AEDs
Antiepileptic drugs
MRI
Magnetic resonance imaging
PPSE
Pharmacoresistant poststroke epilepsy
VNS
Vagal nerve stimulation
Disclosure The authors report no conflict of interest regarding the materials or methods used in this study or the findings specified in this paper.
S1878-8750(19)32479-9
DOI:
https://doi.org/10.1016/j.wneu.2019.09.049
Reference:
WNEU 13348
To appear in:
World Neurosurgery
Received Date: 28 July 2019 Revised Date:
8 September 2019
Accepted Date: 9 September 2019
Please cite this article as: Kubota Y, Nakamoto H, Miyao S, Kawamata T, Efficacy of vagal nerve stimulation for pharmacoresistant poststroke epilepsy, World Neurosurgery (2019), doi: https:// doi.org/10.1016/j.wneu.2019.09.049. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
Efficacy of vagal nerve stimulation for pharmacoresistant poststroke epilepsy
Yuichi Kubotaa,b *, Hidetoshi Nakamotoa,b, Satoru Miyaoa,b, Takakazu Kawamatab a
Department of Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical Center,
Saitama, Japan b
Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan
*
Corresponding author:
Yuichi Kubota Department of Neurosurgery, Stroke and Epilepsy Center, TMG Asaka Medical Center 1-1340 Mizonuma, Asaka, Saitama Phone: +81-48-466-2055 Fax: +81-48-466-2059 Email: [email protected]
Highest academic degrees for all authors Yuichi Kubota, M.D., D.Med.Sci : [email protected]
Hidetoshi Nakamoto, M.D. : [email protected] Satoru Miyao, M.D. : [email protected] Takakazu Kawamata, M.D., Ph.D. : [email protected] Keywords: antiepileptic drugs; poststroke epilepsy; seizure; vagal nerve stimulation
Short title: VNS for poststroke epilepsy
Kubota
Abstract Background: Vagal nerve stimulation (VNS) is an alternative palliative therapy for pharmacoresistant epilepsy. It has been reported to be effective for both focal and generalized epilepsy; however, most of the relevant studies have involved children or young patients. Some patients develop intractable epilepsy after stroke, despite taking antiepileptic drugs (AEDs). In this study, we investigated the efficacy of VNS for pharmacoresistant poststroke epilepsy (PPSE). Methods: We retrospectively studied 10 patients who underwent vagal nerve stimulator implantation for poststroke epilepsy after the seizures had proved refractory to appropriate AEDs. The seizure outcome was evaluated using the McHugh classification 2 years after the implantation. Results: In total, 4 (40%) patients remained seizure-free throughout the 2-year duration. In addition, seizures were reduced by >50% after 2 years in 6(60%) patients. McHugh classification was Class I for 5 patients and Class II for 5 patients. Neither intraoperative complications nor postoperative adverse effects were reported. The average intensity of VNS was 1.75 mA. Conclusions: In this small study, VNS proved to be a safe and effective therapy for PPSE. Patients with poststroke epilepsy experience physical or mental decline; therefore, it is important to control seizures in them to avoid deterioration in their quality of daily life. 1
Kubota
Introduction The development of tissue plasminogen activators and endovascular thrombectomy has drastically reduced mobility problems and mortality following ischemic stroke.1,2 Furthermore, advancements in microsurgical techniques and endovascular coiling for subarachnoid hemorrhage have improved patient outcomes. However, the number of stroke survivors has been increasing every year, and these patients can experience various poststroke complications, such as hemiparesis, aphasia, depression, and epilepsy. Epilepsy is often observed after a stroke, with a prevalence of 2%–10%.3,4 In most patients with poststroke epilepsy, the seizures can be well controlled with suitable antiepileptic drugs (AEDs). However, some patients experience uncontrolled seizures despite taking AEDs. Such pharmacoresistant poststroke epilepsy (PPSE) is relatively rare, but it can pose problems to the patients in their daily lives. Following a stroke, many patients become functionally or socially disabled; therefore, a seizure may require them to be readmitted to hospitals and to undergo long-term rehabilitation. Vagal nerve stimulation (VNS) is a therapeutic option for both generalized and focal epilepsy. It can reduce seizures without craniotomy and is being increasingly widely used.5,6 Unlike medical treatments, VNS does not cause sleepiness or dizziness; thus, it is safe for patients with poststroke epilepsy. In this study, we aimed to examine the efficacy and safety of VNS for patients with PPSE. 2
Kubota
Materials and Methods Patients In this retrospective study, we reviewed data for patients with poststroke epilepsy who attended our stroke and epilepsy center between April 2012 and March 2018 and identified consecutive patients with PPSE, defined as uncontrolled seizures despite taking at least two appropriate AEDs for more than 1 year. All the patients had undergone phase I study including magnetic resonance imaging (MRI) and video electroencephalography monitoring; however, none of them were eligible for surgical resection because the epileptogenic zone in them was located in eloquent areas. Seizure semiology in all patients was either focal onset type, such as a hemiconvulsion, or a secondary generalized type.
Procedure and analysis Vagal nerve stimulator implantation was performed under general anesthesia after obtaining patients’ written informed consent. The VNS generator was implanted in the left upper chest. Two electrodes were attached to the left vagus nerve; the electrodes were connected to an implantable pulse generator. The VNS device used in all patients was model 104 generator (RivaNova Inc., Houston, Tx, U.S.A). The devices were implanted by appropriately trained neurosurgeons. From 2 weeks after the implantation, the patients were administered an 3
Kubota
electrical current that was increased from 0.25 mA to a level that proved adequate for controlling the patients’ seizures (maximum 2.0 mA). The other parameters were same for all the patients: pulse width, 0.5 µs; signal frequency, 30 Hz; signal on time, 30 s; and signal off time, 5 min. Postoperative follow-up period was a minimum of 2 years to a maximum of 7 years. The average follow-up period was 4 years. Seizure outcomes 2 years after the implantation were compared with the rate of seizures before implantation using the Engel and McHugh classifications, which are commonly used for evaluating seizure outcomes.7
Results Table 1 summarizes the characteristics of the 10 patients and the outcomes following the vagal nerve stimulator implantation. The age ranged from 23 to 72, with an average of 64.5. There were 5 cases of cerebral hemorrhage, 3 cases of subarachnoid hemorrhage and 1 case of cerebral infarction. In total, 4 (40%) patients remained seizure-free over the 2 years, and >50% reduction in seizure frequency was observed after 2 years in 6 (60%) patients. McHugh classification was Class I for 5 patients and Class II for 5 patients. The average intensity of VNS was 1.75 mA (1.25–2.0 mA). There were no intraoperative complications, and none of the patients dropped out during the follow-up period. Among the 10 patients magnets were used by 7 patients or by their caregivers to activate the stimulator and abort a seizure at a time that they had the impression that a seizure was developing. 4
Kubota
No.
Sex
1
F
2
Age at VNS
Duration from stroke onset to
Stroke type
Involved region
70
SAH
Left Temporal
7
F
68
ICH
Right Frontal
5
3
F
70
CI
Left Frontal
6
4
M
64
ICH
Left Frontal
1
5
F
71
SAH
Left Temporal
10
6
F
62
SAH
Left Frontal
8
7
M
65
ICH
Right Parietal
77
8
M
23
ICH
Left Parietal
0
9
M
80
ICH
Left Temporal
36
10
M
72
SAH
Right Temporal
7
implantation
seizure onset (months)
Abbreviations: AEDs, antiepileptic drugs; CBZ, carbamazepine; CI, cerebral infarction; ICH, intracerebral he
Discussion This study was the first to report the seizure outcomes of VNS for patients with PPSE over 2 years. VNS was found to be extremely effective for these patients. Seizures in all the patients were well controlled by VNS, despite not being controlled by several adequate AEDs. In addition, some patients remained completely seizure-free. The reason for VNS being effective in patients with PPSE is that these patients had a relatively shorter seizure duration; the duration from epilepsy onset to vagal nerve stimulator implantation was on average 70 months, which is extremely short compared with the period 5
Kubota
of onset of refractory epilepsy in cases with childhood-onset epilepsy. The development of poststroke epilepsy reported requires several months to years.8 Therefore, there is a possibility that strong epileptogenesis seems to be difficult to be formed. In addition, VNS is advantageous for patients with PPSE because poststroke epilepsy has a focal onset and may be associated with aura; thus, patients are able to control seizures by themselves using a magnet. In fact, in 7 of the 10 patients in this study, magnets were sometimes used by the patients themselves or by their caregivers at the time of seizure onset or after the appearance of a sign of seizure. Morri et al. also reported that approximately half of the patients who used the magnet gained some benefit.9 Usually seizures in most of the patients with poststroke epilepsy are controlled with adequate AEDs such as carbamazepine, levetiracetam, and lacosamide, but some patients progress to a refractory condition. Such patients with PPSE sometimes inevitably take a high amount of AEDs to control their seizure. Nonetheless, they may suffer a seizure and are forced to get hospitalized urgently. Long-term hospitalization or transfer to a rehabilitation hospital may be necessary in such patients due to physical condition decline. Thus, in patients with PPSE, VNS therapy can be effectively used without any adverse effects unlike that with AEDs. The limitations of this study were the small number of patients and its non-prospective nature. Further research is needed to better understand the therapeutic role of VNS in patients with PPSE. In addition, this study cannot describe the relationship between seizure reduction and 6
Kubota
stroke types or regions, and further accumulation of cases should be needed. And currently, VNS is not compatible with MRI; this can be problematic if MRI is needed, as some poststroke patients occasionally need to undergo MRI for the diagnosis of ischemic stroke.
Conclusions VNS offers a potentially safe and effective treatment option for patients with PPSE. If seizures are not controlled using AEDs, introduction of VNS should be considered at an early stage from a physical and economic point of view.
Acknowledgements We gratefully appreciated Miss Yuina Nishimura for her assistance. Declarations of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
7
Kubota
References 1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 14;333(24):1581-7. 2. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al., Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 11;372(24):2285-95. 3. Roivainen R, Haapaniemi E, Putaala J, Kaste M, Tatlisumak T. Young adult ischemic stroke related acute symptomatic and late seizures: risk factors. Eur J Neurol. 2013;20:1247-55. 4. Graham NS, Crichton S, Koutroumanidis M, Wolfe CD, Rudd AG. Incidence and associations of poststroke epilepsy: the prospective South London Stroke Register. Stroke. 2013;44:605-11. 5. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia 1998;39:677–86. 6. Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol;2002:1:477–82. 7. McHugh JC, Singh HW, Phillips J, Murphy K, Doherty CP, Delanty N: Outcome measurement after vagal nerve stimulation therapy: proposal of a new classification. Epilepsia. 2007;48:375-8. 8
Kubota
8. Pitkänen A, Roivainen R, Lukasiuk K. Development of epilepsy after ischaemic stroke. Lancet Neurol. 2016;15(2):185-197. 9. Morris GL 3rd. A retrospective analysis of the effects of magnet‐ activated stimulation in conjunction with vagus nerve stimulation therapy. Epilepsy Behav 2003;4:74
9
Kubota
10
No. Sex
Age at VNS implantation
Stroke type
Involved region
Duration from stroke onset to seizure onset (months)
Duration from seizure onset to implantation (months)
Current AEDs
Preoperative seizure frequency
VNS intensity (mA)
Postoperative follow-up periods (year)
Postoperative Engel classifica McHugh seizure tion classification frequency
7
Yearly
IIB
Magnet use
1
F
70
SAH
Left Temporal
7
109
LEV3000, LTG400, CBZ300
Monthly
2.00
II
Yes
2
F
68
ICH
Right Frontal
5
30
VPA400, ZNS200, PB60
Monthly
2.00
6
Yearly
3
F
70
CI
Left Frontal
6
15
VPA400, LEV10000
Monthly
1.50
6
None
IB
I
Yes
IA
I
4
M
64
ICH
Left Frontal
1
29
LEV1000, CBZ400
Monthly
1.50
5
None
IA
No
I
Yes
5
F
71
SAH
Left Temporal
10
51
LEV3000, CBZ200, LTG200
Monthly
2.00
4
Yearly
IIB
II
Yes
6
F
62
SAH
Left Frontal
8
30
LEV3000, ZNS200, PHT200
Monthly
1.75
4
Monthly
IIIA
II
Yes
7
M
65
ICH
Right Parietal
77
92
LEV3000, CBZ400
Monthly
2.00
2
Monthly
IIIA
II
Yes
8
M
23
ICH
Left Parietal
0
61
LEV3000, CBZ700
Monthly
1.25
2
None
IB
I
Yes
9
M
80
ICH
Left Temporal
36
268
LCM100, LEV3000
Monthly
1.50
2
None
IA
I
No
10
M
72
SAH
Right Temporal
7
14
LCM400, GBP1200
Monthly
2.00
2
Yearly
IIA
II
No
Abbreviations: AEDs, antiepileptic drugs; CBZ, carbamazepine; CI, cerebral infarction; ICH, intracerebral hemorrhage; LCM, lacosamide; LEV, levetiracetam; LTG, lamotrigine; PB, phenobarbital; PHT, phenytoin; SAH, subarachnoid hemorrhage; VPA, valproate; VNS, vagal nerve stimulation; ZNS, zonisamide Monthly’ : 2-12 seizures per year. ‘Yearly’ : 0-1 seizure per year
n; ZNS, zonisamide
Abbreviations list AEDs
Antiepileptic drugs
MRI
Magnetic resonance imaging
PPSE
Pharmacoresistant poststroke epilepsy
VNS
Vagal nerve stimulation
Disclosure The authors report no conflict of interest regarding the materials or methods used in this study or the findings specified in this paper.