De novo epilepsy after microsurgical resection of brain arteriovenous malformations

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  • 1 Departments of Neurological Surgery,
  • | 2 Radiology, and
  • | 3 Mechanical Engineering; and
  • | 4 Stroke & Applied Neuroscience Center, University of Washington, Seattle, Washington
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OBJECTIVE

Seizures are the second most common presenting symptom of brain arteriovenous malformations (bAVMs) after hemorrhage. Risk factors for preoperative seizures and subsequent seizure control outcomes have been well studied. There is a paucity of literature on postoperative, de novo seizures in initially seizure-naïve patients who undergo resection. Whereas this entity has been documented after craniotomy for a wide variety of neurosurgically treated pathologies including tumors, trauma, and aneurysms, de novo seizures after bAVM resection are poorly studied. Given the debilitating nature of epilepsy, the purpose of this study was to elucidate the incidence and risk factors associated with de novo epilepsy after bAVM resection.

METHODS

A retrospective review of patients who underwent resection of a bAVM over a 15-year period was performed. Patients who did not present with seizure were included, and the primary outcome was de novo epilepsy (i.e., a seizure disorder that only manifested after surgery). Demographic, clinical, and radiographic characteristics were compared between patients with and without postoperative epilepsy. Subgroup analysis was conducted on the ruptured bAVMs.

RESULTS

From a cohort of 198 patients who underwent resection of a bAVM during the study period, 111 supratentorial ruptured and unruptured bAVMs that did not present with seizure were included. Twenty-one patients (19%) developed de novo epilepsy. One-year cumulative rates of developing de novo epilepsy were 9% for the overall cohort and 8.5% for the cohort with ruptured bAVMs. There were no significant differences between the epilepsy and no-epilepsy groups overall; however, the de novo epilepsy group was younger in the cohort with ruptured bAVMs (28.7 ± 11.7 vs 35.1 ± 19.9 years; p = 0.04). The mean time between resection and first seizure was 26.0 ± 40.4 months, with the longest time being 14 years. Subgroup analysis of the ruptured and endovascular embolization cohorts did not reveal any significant differences. Of the patients who developed poorly controlled epilepsy (defined as Engel class III–IV), all had a history of hemorrhage and half had bAVMs located in the temporal lobe.

CONCLUSIONS

De novo epilepsy after bAVM resection occurs at an annual cumulative risk of 9%, with potentially long-term onset. Younger age may be a risk factor in patients who present with rupture. The development of poorly controlled epilepsy may be associated with temporal lobe location and a delay between hemorrhage and resection.

ABBREVIATIONS

bAVM = brain arteriovenous malformation; RAGS = Ruptured Arteriovenous Malformation Grading Scale.

OBJECTIVE

Seizures are the second most common presenting symptom of brain arteriovenous malformations (bAVMs) after hemorrhage. Risk factors for preoperative seizures and subsequent seizure control outcomes have been well studied. There is a paucity of literature on postoperative, de novo seizures in initially seizure-naïve patients who undergo resection. Whereas this entity has been documented after craniotomy for a wide variety of neurosurgically treated pathologies including tumors, trauma, and aneurysms, de novo seizures after bAVM resection are poorly studied. Given the debilitating nature of epilepsy, the purpose of this study was to elucidate the incidence and risk factors associated with de novo epilepsy after bAVM resection.

METHODS

A retrospective review of patients who underwent resection of a bAVM over a 15-year period was performed. Patients who did not present with seizure were included, and the primary outcome was de novo epilepsy (i.e., a seizure disorder that only manifested after surgery). Demographic, clinical, and radiographic characteristics were compared between patients with and without postoperative epilepsy. Subgroup analysis was conducted on the ruptured bAVMs.

RESULTS

From a cohort of 198 patients who underwent resection of a bAVM during the study period, 111 supratentorial ruptured and unruptured bAVMs that did not present with seizure were included. Twenty-one patients (19%) developed de novo epilepsy. One-year cumulative rates of developing de novo epilepsy were 9% for the overall cohort and 8.5% for the cohort with ruptured bAVMs. There were no significant differences between the epilepsy and no-epilepsy groups overall; however, the de novo epilepsy group was younger in the cohort with ruptured bAVMs (28.7 ± 11.7 vs 35.1 ± 19.9 years; p = 0.04). The mean time between resection and first seizure was 26.0 ± 40.4 months, with the longest time being 14 years. Subgroup analysis of the ruptured and endovascular embolization cohorts did not reveal any significant differences. Of the patients who developed poorly controlled epilepsy (defined as Engel class III–IV), all had a history of hemorrhage and half had bAVMs located in the temporal lobe.

CONCLUSIONS

De novo epilepsy after bAVM resection occurs at an annual cumulative risk of 9%, with potentially long-term onset. Younger age may be a risk factor in patients who present with rupture. The development of poorly controlled epilepsy may be associated with temporal lobe location and a delay between hemorrhage and resection.

Epilepsy is a debilitating disease and, when uncontrolled, can be lethal.1 The association between brain arteriovenous malformations (bAVMs) and epilepsy has been well established.2–9 Seizures are the second most common presenting symptom for bAVMs after hemorrhage, occurring in 20%–45% of cases.2–5 Given the evidence supporting seizure control after bAVM resection, many neurosurgeons consider epilepsy of any degree associated with an unruptured bAVM to be an indication for intervention, with either radiosurgery or microsurgery.10–12 The pathophysiological mechanism behind epileptogenesis in bAVMs is likely to be multifactorial, with theories including hemosiderin deposition, ischemia from blood flow shunting, local gliosis, and kindling.13–15 Whereas seizure control after definitive management of bAVMs in patients who presented with seizures has been thoroughly studied,3,10–12,16–18 the occurrence of de novo epilepsy (in which seizure onset occurs after microsurgical resection) has not been investigated.

De novo epilepsy rates after craniotomy vary widely depending on the indication and pathology involved. For tumors, rates range from 12.1% for meningiomas up to 50% for gliomas.19,20 In the heterogeneous population of patients with neurotrauma, postcraniotomy epilepsy rates range from 5.1% to 17%.21,22 More analogous to bAVMs, de novo epilepsy after craniotomy for ruptured intracranial aneurysms is approximately 10% with independent risk factors such as the presence of intracerebral hemorrhage and worse presenting Hunt and Hess score.23,24 The purpose of this study was to investigate the development of de novo epilepsy after craniotomy for microsurgical resection of bAVMs.

Methods

Patient Population

Institutional review board approval was obtained per the guidelines of the University of Washington School of Medicine. For the period from January 1, 2006, to January 1, 2019, we identified all patients who underwent craniotomy for resection of bAVM at Harborview Medical Center. Patients were excluded if they presented with or had evidence of preoperative seizures, if the bAVM was infratentorial, or if they had less than 1 year of adequate clinical follow-up. All patients received intraoperative phenytoin and postoperative antiepileptic drugs (levetiracetam or phenytoin) for up to 6 weeks for seizure prophylaxis as an institutional standard.

A retrospective chart review was conducted in the resulting group of patients for demographic, clinical, and radiographic data. The patients were separated into two groups: those with no evidence of postoperative seizures and those who developed de novo epilepsy. Epilepsy was defined as the occurrence of partial or generalized seizures at any point after surgery and requiring treatment with antiepileptic drugs under the guidance of a neurologist or epileptologist. Seizure semiology included visual auras, focal motor seizures, and generalized tonic-clonic seizures. A positive electroencephalogram was not required because in the majority of cases the diagnosis of seizures was made based on clinical grounds. The de novo epilepsy group was further subdivided based on Engel class for postoperative seizure control in order to delineate the severity of epilepsy. A subgroup analysis of patients with bAVM rupture and those who underwent preresection endovascular embolization was also conducted. Both rupture of the nidus and rupture of flow-related or intranidal aneurysms were considered in the rupture group.

Outcomes

The epilepsy and no-epilepsy groups were compared to identify characteristics that may be associated with the development of de novo epilepsy (Table 1). The modified frailty index25 was used to estimate each patient’s systemic health and is calculated based on age and presence of medical comorbidities such as diabetes and congestive heart failure. Radiographic characteristics of bAVMs including Spetzler-Martin grade26 and the presence of high-risk features such as intranidal aneurysms and venous outflow stenosis/varices were determined based on digital subtraction angiography. bAVM location was determined by CT angiography or MRI. Patients who required additional surgical procedures for residual bAVM, hematoma evacuation, surgical site infection, and/or cranioplasty were classified as undergoing repeat surgery. Relevant medical complications included meningitis, ventriculitis, or dural venous sinus thrombosis.

TABLE 1.

Comparison of demographic and clinical characteristics in patients who developed epilepsy postoperatively after treatment of AVM versus those who did not (total population)

No Epilepsy, n = 90De Novo Epilepsy, n = 21p Value
Age in yrs, mean ± SD35.1 ± 19.928.7 ± 11.70.057
Sex (%) ref: male0.62
 Male53 (58.9)14 (66.7)
 Female37 (41.1)7 (33.3)
mFI >0 (%)24 (26.7)3 (14.3)0.27
History of hemorrhage (%)66 (73.3)15 (71.4)0.99
AVM location (%)0.56
 Temporal17 (18.9)5 (23.8)
 Extratemporal73 (81.1)16 (76.2)
SM grade, mean ± SD2.1 ± 0.92.5 ± 0.70.05
Eloquent location (%)40 (44.4)11 (52.4)0.32
Deep venous drainage (%)33 (36.7)7 (33.3)0.99
Size (%)*
 <3 cm26 (28.9)10 (47.6)0.99
 3–6 cm62 (68.9)9 (42.9)
 >6 cm0 (0.0)0 (0.0)
Nidal aneurysm (%)10 (11.1)2 (9.5)0.99
Venous stenosis (%)11 (12.2)0 (0.0)0.21
Preop embolization, yes/no (%)57 (63.3)13 (61.9)0.99
History of SRS (%)4 (4.4)1 (4.8)0.99
Time in mos btwn op & first Sz, mean ± SDNA26.0 ± 40.4NA
Complete obliteration (%)87 (96.7)19 (90.5)0.24
Repeat surgery (%)13 (14.4)1 (4.8)0.46
Medical complication (%)6 (6.7)1 (4.8)0.99

mFI = modified frailty index; NA = not applicable; SM = Spetzler-Martin; SRS = stereotactic radiosurgery; Sz = seizure. Student’s t-test was used for continuous variables, and the chi-square and Fisher exact tests were used for categorical variables. p < 0.05 was used as a threshold for statistical significance.

Size data not available for all patients.

For the subgroup analysis of patients with ruptured bAVM, the characteristics being compared can be seen in Table 2. The Ruptured Arteriovenous Malformation Grading Scale (RAGS) was used to estimate the severity of the condition and the prognosis of the patient.27 The RAGS score is calculated using the Hunt and Hess score, patient age, presence of deep venous drainage, and involvement of eloquent cortex. Intraparenchymal hemorrhage volume was calculated using the ABC/2 method based on diameters measured on CT scans. A similar subgroup analysis was conducted for patients who underwent preoperative endovascular embolization, as seen in Table 3.

TABLE 2.

Comparison of demographic and clinical characteristics in patients who developed epilepsy postoperatively after treatment of ruptured AVM versus those who did not (ruptured population)

No Epilepsy, n = 66De Novo Epilepsy, n = 15p Value
Age in yrs, mean ± SD36.0 ± 20.727.8 ± 10.50.04*
Sex (%) ref: male0.57
 Male41 (62.1)7 (46.7)
 Female25 (37.9)8 (53.3)
mFI >0 (%)13 (19.7)2 (13.3)0.33
AVM location (%)0.29
 Temporal12 (18.2)5 (33.3)
 Extratemporal54 (81.8)10 (66.7)
SM grade, mean ± SD2.1 ± 0.92.3 ± 0.70.47
Eloquent location (%)30 (45.5)6 (40.0)0.99
Deep venous drainage (%)28 (42.4)6 (40.0)0.99
Size (%)0.21
 <3 cm49 (74.2)8 (53.3)
 3–6 cm17 (25.8)6 (40.0)
 >6 cm0 (0.0)0 (0.0)
Nidal aneurysm (%)8 (12.1)2 (13.3)0.61
Venous stenosis (%)10 (15.2)0 (0.0)0.34
Preop embolization, yes/no (%)39 (59.1)8 (53.3)0.78
History of SRS (%)2 (3.0)1 (6.7)0.44
Time in mos btwn op & first Sz, mean ± SDNA15.2 ± 19.1NA
Vol of IPH in mm3, mean ± SD18.9 ± 13.617.4 ± 10.30.49
RAGS score, mean ± SD4.4 ± 1.63.6 ± 1.50.08
Time in days btwn rupture & op, mean ± SD8.2 ± 57.329.7 ± 57.30.40
Complete obliteration (%)64 (96.9)13 (86.7)0.23
Repeat surgery (%)11 (16.7)1 (6.7)0.45
Medical complication (%)6 (9.1)1 (6.7)0.99

IPH = intraparenchymal hemorrhage. Student’s t-test was used for continuous variables, and the chi-square and Fisher exact tests were used for categorical variables. p < 0.05 was used as a threshold for statistical significance.

Statistically significant.

TABLE 3.

Comparison of demographic and clinical characteristics in patients who developed epilepsy postoperatively after treatment of embolized bAVM versus those who did not

No Epilepsy, n = 57De Novo Epilepsy, n = 13p Value
Age in yrs, mean ± SD33.9 ± 19.029.7 ± 10.70.28
Sex (%) ref: male0.06
 Male31 (54.4)11 (84.6)
 Female26 (45.6)2 (15.4)
mFI >0 (%)14 (24.6)1 (7.7)
History of hemorrhage (%)39 (68.4)8 (61.5)0.75
AVM location (%)0.99
 Temporal8 (14.0)2 (15.4)
 Extratemporal49 (86.0)11 (84.6)
SM grade, mean ± SD2.4 ± 1.02.5 ± 0.60.44
Eloquent location (%)31 (54.4)7 (53.8)0.99
Deep venous drainage (%)23 (40.4)3 (23.1)0.99
Size (%)0.54
 <3 cm32 (56.1)6 (46.2)
 3–6 cm23 (40.4)7 (53.8)
 >6 cm0 (0.0)0 (0.0)
Nidal aneurysm (%)8 (14.0)1 (7.7)0.99
Venous stenosis (%)10 (17.5)0 (0.0)0.34
History of SRS (%)3 (5.3)0 (0.0)0.99
Time in mos btwn op & first Sz, mean ± SDNA15.2 ± 18.6
Complete obliteration (%)55 (96.5)12 (92.3)0.57
Repeat surgery (%)8 (14.0)1 (7.7)0.99
Medical complication (%)2 (3.5)1 (7.7)0.47

Student’s t-test was used for continuous variables, and the chi-square and Fisher exact tests were used for categorical variables. p < 0.05 was used as a threshold for statistical significance.

Statistical Methods

Statistical analysis was performed using R (version 4.0.3, R Statistical Computing). Data were reported as means with standard deviations for continuous variables and as frequencies (percentages) for categorical variables. Student t-tests were used for comparison of means for continuous variables. Fisher’s exact test and the chi-square test were used for comparison of categorical variables. An association between clinical variables and primary and secondary postoperative outcomes was analyzed using univariate logistic regression analyses.

Results

Of the 198 patients who underwent microsurgical resection of bAVMs during the study period, 87 (44%) were excluded based on occurrence of preoperative seizures, infratentorial location, and inadequate follow-up (Fig. 1). Of the 111 remaining patients, 21 developed de novo epilepsy. A comparison of characteristics between the no-epilepsy and de novo epilepsy groups can be seen in Table 1. There were no statistically significant differences between the two groups. For the de novo epilepsy group, the mean time between resection and first seizure was 26 ± 40.4 months. Rates of gross-total resection were similar between the de novo epilepsy and no-epilepsy groups (90.5% vs 96.7%; p = 0.24). Both patients in the de novo epilepsy group who had partial resections due to proximity to eloquent cortex (language and motor) underwent Gamma Knife radiosurgery to address the residual disease. One patient had seizure onset prior to initiation of Gamma Knife treatment, whereas the other had onset after angiographic cure was established.

FIG. 1.
FIG. 1.

Study flow diagram showing patient inclusion and exclusion criteria.

Of the 81 patients with bAVM rupture, 15 developed de novo epilepsy, with a 1-year cumulative rate of 8.5%. A comparison of characteristics between patients with no epilepsy and those with de novo epilepsy within the ruptured bAVM group can be seen in Table 2. The de novo epilepsy group was statistically younger than the no-epilepsy group, with a mean age of 27.8 ± 10.5 versus 36.0 ± 20.7 years (p = 0.04). Otherwise, there were no differences in clinical or radiographic characteristics.

Comparison between patients with poorly controlled de novo epilepsy (defined as Engel class III–IV) and patients with no seizures or well-controlled de novo epilepsy (defined as Engel class I–II) can be seen in Table 4. Three of 6 patients (50%) with Engel class III–IV epilepsy had lesions located in the temporal lobe, and these patients had longer delays between rupture and resection (32.5 ± 61.6 days vs 7.9 ± 12.3 days); however, these delays did not reach statistical significance.

TABLE 4.

Comparison of clinical variables of patients without seizures and Engel class I–II versus Engel class III–IV

No Szs or Engel Class I–II, n = 105Engel Class III–IV, n = 6p Value
Ruptured (%)75 (71.4)6 (100.0)0.19
RAGS score, mean ± SD4.2 ± 1.53.5 ± 1.40.32
Location, temporal vs extratemporal (%)20 (19.0)3 (50.0)
IPH vol, mean ± SD20.8 ± 17.621.7 ± 5.60.79
Time in days btwn rupture & op, mean ± SD7.9 ± 12.332.5 ± 61.60.41
Time in mos btwn op & first Sz, mean ± SD29.4 ± 44.713.7 ± 25.20.36
Complete obliteration (%)100 (95.2)6 (100.0)0.99
Repeat surgery (%)14 (13.3)0 (0.0)0.99

Student’s t-test was used for continuous variables, and the chi-square and Fisher exact tests were used for categorical variables. p < 0.05 was used as a threshold for statistical significance.

The additional subgroup analysis of patients who underwent preoperative endovascular embolization versus those who did not failed to reveal any underlying risk factors.

Discussion

This study suggests that there is a population of initially seizure-naïve patients who undergo craniotomy for resection of bAVMs and who develop new-onset epilepsy in a delayed fashion. This is a rare but clinically relevant population of patients treated surgically for bAVMs.

Overall Incidence

One of the notable findings of this study is the relatively high rate of de novo epilepsy. Of the 111 seizure-naïve patients with bAVM, 18.9% experience de novo epilepsy after craniotomy for resection, and the 1-year cumulative risk was calculated at 9%. Given the exclusion of patients with inadequate follow-up, this may represent a slight overestimation. However, to our knowledge, there are no other studies that report on this phenomenon in bAVMs.

Both intrinsic and extrinsic brain tumors are similar to bAVMs in that they are space-occupying intracranial lesions. Xue et al. found a 2-year cumulative seizure rate after meningioma resection of 14%.20 In glioblastoma, reported de novo epilepsy rates range from 23.6%28 up to 50%,19 and show a clear correlation with extent of resection. These neoplastic processes are inherently different from bAVMs in their interaction with cortical and subcortical tissue. Several studies have shown that the infiltrative nature of gliomas and higher-grade meningiomas that have evidence of brain invasion on pathological investigation lead to higher rates of pre- and postoperative epilepsy.19,29–31 Thorough resection of these lesions may require more disruption of the surrounding parenchyma, which may explain the slightly higher rates of new, postresection epilepsy. bAVMs are not infiltrative lesions and may cause seizures via different mechanisms, such as microhemorrhage or vascular steal phenomena.13,14,32

Steal physiology is an important concept to address in the discussion of seizure etiology pre- and postresection of bAVMs. In theory, bAVM niduses, in particular large ones, create a low-resistance vascular bed that redirects blood volume from local, normal brain.33–35 Although difficult to prove definitively, an association between hemodynamic changes and epilepsy has been suggested. For example, one study has identified radiographic deficits in local cerebral autoregulation of bAVMs in patients with seizures compared to those without.36 Although such objective studies on the postresection population do not exist, it is theoretically possible that these chronic hemodynamic alterations to adjacent brain persist even after complete obliteration of the bAVM nidus, leaving patients susceptible to developing epilepsy in the long term, especially in the setting of other physiological stressors such as sleep deprivation and alcohol consumption.37

Notably, there was a wide range of timing of the onset of de novo epilepsy in this cohort—from several days up to 14 years postoperatively. It is possible that there exist distinct causes of de novo epilepsy in patients with bAVM—those related to antiepileptic prophylaxis in the immediate postoperative period, and those related to encephalomalacia and gliosis in the long term; however, a larger data set would be required to address the true distribution of de novo epilepsy.

Ruptured bAVM Cohort

Ruptured bAVMs may represent a distinct entity from unruptured bAVMs with regard to epilepsy. Although other studies have shown a history of hemorrhage to be a risk factor for preoperative seizures,10 its effect on the development of postoperative de novo epilepsy is unclear. Our data did not show a correlation between history of hemorrhage of any kind and de novo epilepsy. Furthermore, subgroup analysis of the ruptured versus unruptured bAVMs revealed a comparable 1-year cumulative risk of de novo epilepsy (8.5% and 10.3%, respectively). These numbers are also consistent with previously reported 1-year rates of between 8% and 9.7% for de novo epilepsy after craniotomy for ruptured intracranial aneurysms.23,24 Of note, none of the patients with ruptured bAVMs suffered a seizure between hemorrhage and resection, with a mean delay in resection of 19.5 days.

Epilepsy itself affects people of all ages, but its incidence peaks with increasing age, due to the higher prevalence of age-related epileptogenic conditions such as stroke and dementia.38 For patients with bAVMs, preoperative seizures have been associated with older age at presentation compared to hemorrhage.9 Although no linear relationship with age has been established, presenting seizures appear to be more common between the ages of 30 and 50 years.9,39–42 In contrast, within the ruptured bAVM cohort, younger age appeared to be an independent risk factor for developing de novo epilepsy. Further studies are necessary to explore this relationship, although it is possible that younger patients had more consistent long-term follow-up, resulting in the identification of those who developed de novo epilepsy long after their bAVM resection.

Risk of Poorly Controlled De Novo Epilepsy

Six patients in this cohort had poorly controlled epilepsy (defined as Engel class III–IV) at follow-up. Although there were no statistically significant differences when compared to those with no seizures or Engel class I–II postoperative epilepsy, there were some notable patterns that are consistent with known risk factors for epilepsy. All 6 patients with poorly controlled epilepsy had a history of hemorrhage, and half had bAVMs located in the temporal lobe. In general, temporal lobe epilepsy is the most common form of adult epilepsy,43,44 and often results from structural abnormalities within the temporal lobe.45 The preponderance of seizures due to lesions of the temporal lobe is thought to be due to its dense interconnectivity between both cortical and neocortical structures.46–50 However, the data on the impact of location on preoperative seizures in patients with bAVMs suggest comparable rates of seizures from lesions within the frontal, temporal, and parietal lobes, with statistically lower rates from lesions in the occipital lobe.4,9,41,51,52 These findings were validated by Tong et al. in their review of more than 3000 bAVMs.9 Thus, the large proportion of patients with de novo epilepsy in this study who had bAVMs in extratemporal regions (76.2%) is consistent with the literature on preoperative seizures and bAVMs. Although temporal lobe location was not identified as an independent risk factor in this study, there was a large proportion of patients with ruptured bAVMs in the temporal lobe who developed poorly controlled epilepsy, suggesting that hemorrhage in this highly epileptogenic region of the brain places these particular patients with bAVM at long-term risk for developing severe epilepsy.

On average, the poorly controlled group had a longer delay between rupture and resection. This may be suggestive of the cytotoxic effects of intracerebral hemorrhage on local neural tissue, given that the metabolic byproducts of hematoma such as heme, iron, and thrombin have all been implicated in neurotoxicity.53–57 It is possible that delaying bAVM resection and hematoma evacuation may result in more neuronal death, gliosis, and inflammation, all of which would increase the risk of developing delayed de novo epilepsy.

We observed a wide range of time to onset of de novo epilepsy. Some patients experienced their first seizure within days of craniotomy, whereas others went several years before their first seizure. The longest time from craniotomy to first seizure was 14.4 years. Few other studies report on long-term de novo epilepsy in the craniotomy population. Giraldi et al. reviewed nearly 9000 patients who underwent craniotomy for any neurosurgically treated pathologies and found cumulative 5-year rates of de novo epilepsy of up to 19.6% and 34.5% for glioblastoma and oligodendroglioma, respectively. For cerebrovascular pathology such as ruptured intracranial aneurysms and all bAVMs, 5-year cumulative rates were 7.8% and 13.2%, respectively.28 The logical conclusion from these limited data is that patients who undergo craniotomy to address a neurosurgically treated lesion have a higher lifetime risk of developing de novo epilepsy than the general population.

Limitations

There are several limitations to this study. Its retrospective nature could lead to selection and observer bias. The small sample size for a relatively rare event limits the statistical power. Inconsistent and limited follow-up negatively impacted the ability to calculate a true incidence of de novo epilepsy and to obtain long-term epilepsy outcomes. Larger, prospective studies will be needed to calculate a more accurate incidence and identify risk factors associated with de novo epilepsy.

Conclusions

Postoperative de novo epilepsy is an underreported phenomenon after bAVM resection, occurring with a 1-year cumulative risk of 9%. For those with ruptured bAVMs, younger age may be an independent risk factor. Temporal lobe location and a longer delay between hemorrhage and resection may be related to more severe, poorly controlled de novo epilepsy.

Disclosures

Dr. Levitt is a consultant for Medtronic, Aeaean Advisers, and Metis Innovative. He has received support of a non–study-related clinical or research effort that he oversaw from Medtronic and Stryker. He has direct stock ownership in Synchron, Cerebrotech, Proprio, Hyperion Surgical, and Fluid Biomed. Dr. Kim has direct stock ownership in SPI Surgical, Inc., and is a consultant for Philips North America.

Author Contributions

Conception and design: Kim, Sen, Nistal, Sekhar, Levitt. Acquisition of data: Sen, McGrath, Barros, Shenoy, Levitt. Analysis and interpretation of data: Sen, Nistal, McGrath. Drafting the article: Sen, Nistal, McGrath, Barros. Critically revising the article: Kim, Nistal, McGrath, Barros, Shenoy, Sekhar, Levitt. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Kim. Statistical analysis: Sen, Nistal. Study supervision: Kim.

References

  • 1

    Cockerell OC, Johnson AL, Sander JWAS, Hart YM, Goodridge DM, Shorvon SD. Mortality from epilepsy: results from a prospective population-based study. Lancet. 1994;344(8927):918921.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Murphy MJ. Long-term follow-up of seizures associated with cerebral arteriovenous malformations. Results of therapy. Arch Neurol. 1985;42(5):477479.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Hoh BL, Chapman PH, Loeffler JS, Carter BS, Ogilvy CS. Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: factors associated with seizure incidence and seizure outcomes. Neurosurgery. 2002;51(2):303311.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Crawford PM, West CR, Shaw MD, Chadwick DW. Cerebral arteriovenous malformations and epilepsy: factors in the development of epilepsy. Epilepsia. 1986;27(3):270275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Josephson CB, Leach JP, Duncan R, Roberts RC, Counsell CE, Al-Shahi Salman R. Seizure risk from cavernous or arteriovenous malformations: prospective population-based study. Neurology. 2011;76(18):15481554.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Schramm J. Seizures associated with cerebral arteriovenous malformations. Handb Clin Neurol.2017;143:3140.

  • 7

    Soldozy S, Norat P, Yağmurlu K, et al. Arteriovenous malformation presenting with epilepsy: a multimodal approach to diagnosis and treatment. Neurosurg Focus. 2020;48(4):E17.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Galletti F, Costa C, Cupini LM, et al. Brain arteriovenous malformations and seizures: an Italian study. J Neurol Neurosurg Psychiatry. 2014;85(3):284288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Tong X, Wu J, Lin F, et al. The effect of age, sex, and lesion location on initial presentation in patients with brain arteriovenous malformations. World Neurosurg. 2016;87:598606.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Englot DJ, Young WL, Han SJ, McCulloch CE, Chang EF, Lawton MT. Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients. Neurosurgery. 2012;71(3):572580.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Chen CJ, Chivukula S, Ding D, et al. Seizure outcomes following radiosurgery for cerebral arteriovenous malformations. Neurosurg Focus. 2014;37(3):E17.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Ding D, Quigg M, Starke RM, et al. Radiosurgery for temporal lobe arteriovenous malformations: effect of temporal location on seizure outcomes. J Neurosurg. 2015;123(4):924934.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Kraemer DL, Awad IA. Vascular malformations and epilepsy: clinical considerations and basic mechanisms. Epilepsia. 1994;35(suppl 6):S30S43.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Leblanc R, Feindel W, Ethier R. Epilepsy from cerebral arteriovenous malformations. Can J Neurol Sci. 1983;10(2):9195.

  • 15

    Yeh HS, Privitera MD. Secondary epileptogenesis in cerebral arteriovenous malformations. Arch Neurol. 1991;48(11):11221124.

  • 16

    Baranoski JF, Grant RA, Hirsch LJ, et al. Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis. J Neurointerv Surg. 2014;6(9):684690.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Ditty BJ, Omar NB, Foreman PM, et al. Seizure outcomes after stereotactic radiosurgery for the treatment of cerebral arteriovenous malformations. J Neurosurg. 2017;126(3):845851.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Przybylowski CJ, Ding D, Starke RM, et al. Seizure and anticonvulsant outcomes following stereotactic radiosurgery for intracranial arteriovenous malformations. J Neurosurg. 2015;122(6):12991305.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Liang S, Zhang J, Zhang S, Fu X. Epilepsy in adults with supratentorial glioblastoma: incidence and influence factors and prophylaxis in 184 patients. PLoS One. 2016;11(7):e0158206.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Xue H, Sveinsson O, Bartek J Jr, et al. Long-term control and predictors of seizures in intracranial meningioma surgery: a population-based study. Acta Neurochir (Wien). 2018;160(3):589596.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Spencer R, Manivannan S, Sharouf F, Bhatti MI, Zaben M. Risk factors for the development of seizures after cranioplasty in patients that sustained traumatic brain injury: a systematic review. Seizure. 2019;69:1116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998;338(1):2024.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Hart Y, Sneade M, Birks J, Rischmiller J, Kerr R, Molyneux A. Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm: results from the International Subarachnoid Aneurysm Trial. J Neurosurg. 2011;115(6):11591168.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Huttunen J, Kurki MI, von Und Zu Fraunberg M, et al. Epilepsy after aneurysmal subarachnoid hemorrhage: a population-based, long-term follow-up study. Neurology. 2015;84(22):22292237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. New 5-factor modified frailty index using American College of Surgeons NSQIP data. J Am Coll Surg. 2018;226(2):173181.e8.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65(4):476483.

  • 27

    Silva MA, Lai PMR, Du R, Aziz-Sultan MA, Patel NJ. The Ruptured Arteriovenous Malformation Grading Scale (RAGS): an extension of the Hunt and Hess scale to predict clinical outcome for patients with ruptured brain arteriovenous malformations. Neurosurgery. 2020;87(2):193199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Giraldi L, Vinsløv Hansen J, Wohlfahrt J, Fugleholm K, Melbye M, Munch TN. Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study. J Neurol Neurosurg Psychiatry. 2022;93(4):436444.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Lee JW, Wen PY, Hurwitz S, et al. Morphological characteristics of brain tumors causing seizures. Arch Neurol. 2010;67(3):336342.

  • 30

    Li L, Li G, Fang S, et al. New-onset postoperative seizures in patients with diffuse gliomas: a risk assessment analysis. Front Neurol. 2021;12:682535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Oushy S, Sillau SH, Ney DE, et al. New-onset seizure during and after brain tumor excision: a risk assessment analysis. J Neurosurg. 2018;128(6):17131718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Wolf HK, Roos D, Blümcke I, Pietsch T, Wiestler OD. Perilesional neurochemical changes in focal epilepsies. Acta Neuropathol. 1996;91(4):376384.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom RA, Zimmerman RS. Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. J Neurosurg. 1992;76(6):918923.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Norris JS, Valiante TA, Wallace MC, et al. A simple relationship between radiological arteriovenous malformation hemodynamics and clinical presentation: a prospective, blinded analysis of 31 cases. J Neurosurg. 1999;90(4):673679.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Taylor CL, Selman WR, Ratcheson RA. Steal affecting the central nervous system. Neurosurgery. 2002;50(4):679689.

  • 36

    Fierstra J, Conklin J, Krings T, et al. Impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations. Brain. 2011;134(Pt 1):100109.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Shneker BF, Fountain NB. Epilepsy. Dis Mon. 2003;49(7):426478.

  • 38

    Beghi E, Giussani G. Aging and the epidemiology of epilepsy. Neuroepidemiology. 2018;51(3-4):216223.

  • 39

    Stapf C, Khaw AV, Sciacca RR, et al. Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation. Stroke. 2003;34(11):26642669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Forster DM, Steiner L, Håkanson S. Arteriovenous malformations of the brain. A long-term clinical study. J Neurosurg. 1972;37(5):562570.

  • 41

    Garcin B, Houdart E, Porcher R, et al. Epileptic seizures at initial presentation in patients with brain arteriovenous malformation. Neurology. 2012;78(9):626631.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Hashimoto H, Iida J, Kawaguchi S, Sakaki T. Clinical features and management of brain arteriovenous malformations in elderly patients. Acta Neurochir (Wien). 2004;146(10):10911098.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43

    Engel J Jr. Mesial temporal lobe epilepsy: what have we learned? Neuroscientist. 2001;7(4):340352.

  • 44

    Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol. 1993;34(6):781787.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45

    Margerison JH, Corsellis JA. Epilepsy and the temporal lobes. A clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain. 1966;89(3):499530.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46

    Bartolomei F, Bosma I, Klein M, et al. Disturbed functional connectivity in brain tumour patients: evaluation by graph analysis of synchronization matrices. Clin Neurophysiol. 2006;117(9):20392049.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47

    Bernhardt BC, Chen Z, He Y, Evans AC, Bernasconi N. Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cereb Cortex. 2011;21(9):21472157.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Bernhardt BC, Hong S, Bernasconi A, Bernasconi N. Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci. 2013;7:624.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49

    Bonilha L, Rorden C, Halford JJ, et al. Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 2007;78(3):286294.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50

    Haneef Z, Lenartowicz A, Yeh HJ, Engel J Jr, Stern JM. Effect of lateralized temporal lobe epilepsy on the default mode network. Epilepsy Behav. 2012;25(3):350357.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51

    Ding D, Starke RM, Quigg M, et al. Cerebral arteriovenous malformations and epilepsy, Part 1: Predictors of seizure presentation. World Neurosurg. 2015;84(3):645652.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52

    Ghossoub M, Nataf F, Merienne L, Devaux B, Turak B, Roux FX. Characteristics of epileptic seizures associated with cerebral arteriovenous malformations. Article in French. Neurochirurgie. 2001;47(2-3 Pt 2):168176.

    • Search Google Scholar
    • Export Citation
  • 53

    Wang J, Liang J, Deng J, et al. Emerging role of microglia-mediated neuroinflammation in epilepsy after subarachnoid hemorrhage. Mol Neurobiol. 2021;58(6):27802791.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54

    Wang J, Zhuang H, Doré S. Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. Neurobiol Dis. 2006;22(3):473476.

  • 55

    Hua Y, Nakamura T, Keep RF, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg. 2006;104(2):305312.

  • 56

    Qiu X, Wu JM, Song SJ. Delayed neuronal degeneration after intracerebral hemorrhage: the role of iron. Article in Chinese. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2009;38(6):572578.

    • Search Google Scholar
    • Export Citation
  • 57

    Sukumari-Ramesh S, Laird MD, Singh N, Vender JR, Alleyne CH Jr, Dhandapani KM. Astrocyte-derived glutathione attenuates hemin-induced apoptosis in cerebral microvascular cells. Glia. 2010;58(15):18581870.

    • Crossref
    • Search Google Scholar
    • Export Citation

Illustration from Agosti et al. (E5). Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.

  • View in gallery

    Study flow diagram showing patient inclusion and exclusion criteria.

  • 1

    Cockerell OC, Johnson AL, Sander JWAS, Hart YM, Goodridge DM, Shorvon SD. Mortality from epilepsy: results from a prospective population-based study. Lancet. 1994;344(8927):918921.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Murphy MJ. Long-term follow-up of seizures associated with cerebral arteriovenous malformations. Results of therapy. Arch Neurol. 1985;42(5):477479.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Hoh BL, Chapman PH, Loeffler JS, Carter BS, Ogilvy CS. Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: factors associated with seizure incidence and seizure outcomes. Neurosurgery. 2002;51(2):303311.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Crawford PM, West CR, Shaw MD, Chadwick DW. Cerebral arteriovenous malformations and epilepsy: factors in the development of epilepsy. Epilepsia. 1986;27(3):270275.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Josephson CB, Leach JP, Duncan R, Roberts RC, Counsell CE, Al-Shahi Salman R. Seizure risk from cavernous or arteriovenous malformations: prospective population-based study. Neurology. 2011;76(18):15481554.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Schramm J. Seizures associated with cerebral arteriovenous malformations. Handb Clin Neurol.2017;143:3140.

  • 7

    Soldozy S, Norat P, Yağmurlu K, et al. Arteriovenous malformation presenting with epilepsy: a multimodal approach to diagnosis and treatment. Neurosurg Focus. 2020;48(4):E17.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Galletti F, Costa C, Cupini LM, et al. Brain arteriovenous malformations and seizures: an Italian study. J Neurol Neurosurg Psychiatry. 2014;85(3):284288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Tong X, Wu J, Lin F, et al. The effect of age, sex, and lesion location on initial presentation in patients with brain arteriovenous malformations. World Neurosurg. 2016;87:598606.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Englot DJ, Young WL, Han SJ, McCulloch CE, Chang EF, Lawton MT. Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients. Neurosurgery. 2012;71(3):572580.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Chen CJ, Chivukula S, Ding D, et al. Seizure outcomes following radiosurgery for cerebral arteriovenous malformations. Neurosurg Focus. 2014;37(3):E17.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Ding D, Quigg M, Starke RM, et al. Radiosurgery for temporal lobe arteriovenous malformations: effect of temporal location on seizure outcomes. J Neurosurg. 2015;123(4):924934.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Kraemer DL, Awad IA. Vascular malformations and epilepsy: clinical considerations and basic mechanisms. Epilepsia. 1994;35(suppl 6):S30S43.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Leblanc R, Feindel W, Ethier R. Epilepsy from cerebral arteriovenous malformations. Can J Neurol Sci. 1983;10(2):9195.

  • 15

    Yeh HS, Privitera MD. Secondary epileptogenesis in cerebral arteriovenous malformations. Arch Neurol. 1991;48(11):11221124.

  • 16

    Baranoski JF, Grant RA, Hirsch LJ, et al. Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis. J Neurointerv Surg. 2014;6(9):684690.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Ditty BJ, Omar NB, Foreman PM, et al. Seizure outcomes after stereotactic radiosurgery for the treatment of cerebral arteriovenous malformations. J Neurosurg. 2017;126(3):845851.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Przybylowski CJ, Ding D, Starke RM, et al. Seizure and anticonvulsant outcomes following stereotactic radiosurgery for intracranial arteriovenous malformations. J Neurosurg. 2015;122(6):12991305.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Liang S, Zhang J, Zhang S, Fu X. Epilepsy in adults with supratentorial glioblastoma: incidence and influence factors and prophylaxis in 184 patients. PLoS One. 2016;11(7):e0158206.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Xue H, Sveinsson O, Bartek J Jr, et al. Long-term control and predictors of seizures in intracranial meningioma surgery: a population-based study. Acta Neurochir (Wien). 2018;160(3):589596.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Spencer R, Manivannan S, Sharouf F, Bhatti MI, Zaben M. Risk factors for the development of seizures after cranioplasty in patients that sustained traumatic brain injury: a systematic review. Seizure. 2019;69:1116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998;338(1):2024.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Hart Y, Sneade M, Birks J, Rischmiller J, Kerr R, Molyneux A. Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm: results from the International Subarachnoid Aneurysm Trial. J Neurosurg. 2011;115(6):11591168.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Huttunen J, Kurki MI, von Und Zu Fraunberg M, et al. Epilepsy after aneurysmal subarachnoid hemorrhage: a population-based, long-term follow-up study. Neurology. 2015;84(22):22292237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. New 5-factor modified frailty index using American College of Surgeons NSQIP data. J Am Coll Surg. 2018;226(2):173181.e8.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65(4):476483.

  • 27

    Silva MA, Lai PMR, Du R, Aziz-Sultan MA, Patel NJ. The Ruptured Arteriovenous Malformation Grading Scale (RAGS): an extension of the Hunt and Hess scale to predict clinical outcome for patients with ruptured brain arteriovenous malformations. Neurosurgery. 2020;87(2):193199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Giraldi L, Vinsløv Hansen J, Wohlfahrt J, Fugleholm K, Melbye M, Munch TN. Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study. J Neurol Neurosurg Psychiatry. 2022;93(4):436444.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Lee JW, Wen PY, Hurwitz S, et al. Morphological characteristics of brain tumors causing seizures. Arch Neurol. 2010;67(3):336342.

  • 30

    Li L, Li G, Fang S, et al. New-onset postoperative seizures in patients with diffuse gliomas: a risk assessment analysis. Front Neurol. 2021;12:682535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Oushy S, Sillau SH, Ney DE, et al. New-onset seizure during and after brain tumor excision: a risk assessment analysis. J Neurosurg. 2018;128(6):17131718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Wolf HK, Roos D, Blümcke I, Pietsch T, Wiestler OD. Perilesional neurochemical changes in focal epilepsies. Acta Neuropathol. 1996;91(4):376384.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom RA, Zimmerman RS. Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. J Neurosurg. 1992;76(6):918923.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Norris JS, Valiante TA, Wallace MC, et al. A simple relationship between radiological arteriovenous malformation hemodynamics and clinical presentation: a prospective, blinded analysis of 31 cases. J Neurosurg. 1999;90(4):673679.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Taylor CL, Selman WR, Ratcheson RA. Steal affecting the central nervous system. Neurosurgery. 2002;50(4):679689.

  • 36

    Fierstra J, Conklin J, Krings T, et al. Impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations. Brain. 2011;134(Pt 1):100109.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Shneker BF, Fountain NB. Epilepsy. Dis Mon. 2003;49(7):426478.

  • 38

    Beghi E, Giussani G. Aging and the epidemiology of epilepsy. Neuroepidemiology. 2018;51(3-4):216223.

  • 39

    Stapf C, Khaw AV, Sciacca RR, et al. Effect of age on clinical and morphological characteristics in patients with brain arteriovenous malformation. Stroke. 2003;34(11):26642669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Forster DM, Steiner L, Håkanson S. Arteriovenous malformations of the brain. A long-term clinical study. J Neurosurg. 1972;37(5):562570.

  • 41

    Garcin B, Houdart E, Porcher R, et al. Epileptic seizures at initial presentation in patients with brain arteriovenous malformation. Neurology. 2012;78(9):626631.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Hashimoto H, Iida J, Kawaguchi S, Sakaki T. Clinical features and management of brain arteriovenous malformations in elderly patients. Acta Neurochir (Wien). 2004;146(10):10911098.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43

    Engel J Jr. Mesial temporal lobe epilepsy: what have we learned? Neuroscientist. 2001;7(4):340352.

  • 44

    Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol. 1993;34(6):781787.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45

    Margerison JH, Corsellis JA. Epilepsy and the temporal lobes. A clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain. 1966;89(3):499530.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46

    Bartolomei F, Bosma I, Klein M, et al. Disturbed functional connectivity in brain tumour patients: evaluation by graph analysis of synchronization matrices. Clin Neurophysiol. 2006;117(9):20392049.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47

    Bernhardt BC, Chen Z, He Y, Evans AC, Bernasconi N. Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cereb Cortex. 2011;21(9):21472157.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Bernhardt BC, Hong S, Bernasconi A, Bernasconi N. Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci. 2013;7:624.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49

    Bonilha L, Rorden C, Halford JJ, et al. Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy. J Neurol Neurosurg Psychiatry. 2007;78(3):286294.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50

    Haneef Z, Lenartowicz A, Yeh HJ, Engel J Jr, Stern JM. Effect of lateralized temporal lobe epilepsy on the default mode network. Epilepsy Behav. 2012;25(3):350357.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51

    Ding D, Starke RM, Quigg M, et al. Cerebral arteriovenous malformations and epilepsy, Part 1: Predictors of seizure presentation. World Neurosurg. 2015;84(3):645652.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52

    Ghossoub M, Nataf F, Merienne L, Devaux B, Turak B, Roux FX. Characteristics of epileptic seizures associated with cerebral arteriovenous malformations. Article in French. Neurochirurgie. 2001;47(2-3 Pt 2):168176.

    • Search Google Scholar
    • Export Citation
  • 53

    Wang J, Liang J, Deng J, et al. Emerging role of microglia-mediated neuroinflammation in epilepsy after subarachnoid hemorrhage. Mol Neurobiol. 2021;58(6):27802791.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54

    Wang J, Zhuang H, Doré S. Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. Neurobiol Dis. 2006;22(3):473476.

  • 55

    Hua Y, Nakamura T, Keep RF, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg. 2006;104(2):305312.

  • 56

    Qiu X, Wu JM, Song SJ. Delayed neuronal degeneration after intracerebral hemorrhage: the role of iron. Article in Chinese. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2009;38(6):572578.

    • Search Google Scholar
    • Export Citation
  • 57

    Sukumari-Ramesh S, Laird MD, Singh N, Vender JR, Alleyne CH Jr, Dhandapani KM. Astrocyte-derived glutathione attenuates hemin-induced apoptosis in cerebral microvascular cells. Glia. 2010;58(15):18581870.

    • Crossref
    • Search Google Scholar
    • Export Citation

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