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Clinical outcome of brainstem arteriovenous malformations after incomplete nidus obliteration
Journal of Clinical Neuroscience 65 (2019) 66–70
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical study
Clinical outcome of brainstem arteriovenous malformations after incomplete nidus obliteration Thomas J. Sorenson a,b, Giuseppe Lanzino b,d, Kelly D. Flemming c, Deena M. Nasr c, Shannon Y. Chiu c, Bruce E. Pollock b, Waleed Brinjikji b,d,⇑ a
School of Medicine, University of Minnesota, Minneapolis, MN, USA Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA Department of Neurology, Mayo Clinic, Rochester, MN, USA d Department of Radiology, Mayo Clinic, Rochester, MN, USA b c
a r t i c l e
i n f o
Article history: Received 21 January 2019 Accepted 8 March 2019
Keywords: Brainstem Arteriovenous malformation Stereotactic radiosurgery Clinical outcome Rupture
a b s t r a c t Purpose: Brainstem arteriovenous malformations (AVMs) present a formidable therapeutic challenge, and a variety of surgical and non-surgical treatment strategies can be used to obliterate the AVM nidus, eliminating its risk of hemorrhage. However, complete obliteration of brainstem AVMs is often not possible. We aimed to investigate the natural history of brainstem AVMs with incomplete nidus obliteration after initial treatment. Methods: Data from consecutive patients who presented to our institution during the study period with a brainstem AVM and residual nidus after treatment were retrospectively reviewed. We evaluated patients for the incidence of AVM rupture and calculated the risk of rupture after treatment resulted in incomplete nidus obliteration. Results: A total of 14 patients were included, five of whom suffered rupture after incomplete nidus obliteration (36%). Annual risk of rupture was 4.9% (95% CI: 1.60–11.5) per patient over a median follow-up of 72 months. The most common treatment modality of these patients was SRS-alone (n = 6), and two (33%) patients who underwent this treatment later ruptured after 103 and 130 months. Of the five patients who ruptured after treatment, 80% had already ruptured once, and 80% had an intranidal and/or feeding artery aneurysm. Conclusions: Brainstem AVMs with incomplete nidus obliteration are at high risk of future rupture. Patients with brainstem AVMs who have a residual nidus after treatment should be counselled about the risk of AVM rupture and be recommended to undergo close follow-up imaging studies to monitor the nidus. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Brainstem arteriovenous malformations (AVMs) are uncommon lesions and present a formidable therapeutic challenge due to their location in eloquent brain. A variety of surgical and non-surgical treatment strategies (i.e. stereotactic radiosurgery [SRS], endovascular embolization) can be used alone or in tandem to obliterate the AVM nidus and eliminate its risk of rupture. However, complete obliteration of brainstem AVMs is often not possible due to the risk of injuring critical neurological structures, and these treatment strategies not infrequently result in incomplete obliteration of the
AVM nidus [1,9,12,13], which may then still be prone to rupture. In our consecutive series of patients with brainstem AVMs with residual nidus after treatment, we aimed to investigate the risk of rupture after incomplete nidus obliteration of a brainstem AVM. 2. Materials and methods This study was approved by our Institutional Review Board and consent was obtained to use clinical information for research purposes. 2.1. Patient identification
⇑ Corresponding author at: Department of Radiology, Neurologic Surgery, 200 1st Street SW, Rochester, MN 55902, USA. E-mail address: [email protected] (W. Brinjikji). https://doi.org/10.1016/j.jocn.2019.03.009 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
We reviewed an author-maintained database of consecutive patients who were diagnosed and/or treated for an AVM at our
67
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institution between January 1, 2000 and July 1, 2018 to identify patients with an AVM nidus located in the brainstem (medulla oblongata, pons, or midbrain). Patients were included in our study if they: (1) agreed to have their information used for research purposes, (2) were evaluated and treated for a brainstem AVM, and (3) had angiographically-confirmed residual nidus after treatment. Post-treatment angiography was performed immediately postoperatively and then against after three years in all included patients. Additional angiographic and/or clinical follow-up was individualized based on patient and AVM characteristics. Patients were excluded if: (1) the location of their AVM nidus was not within the brainstem, (2) their AVM was not treated, or (3) their AVM had angiographically-documented complete nidus obliteration after treatment.
2.2. Data collection Data were collected based on clinical and radiographic chart review. Collected data included: patient demographics (sex, age), AVM characteristics (size, location, feeding arteries, hemorrhage status, hemorrhage location, involved lesion tissue, feeding artery, feeding artery/intranidal aneurysm, presence of venous varix, presence of multiple draining veins, visibility on MRI, terminal or en passage nidus, presence of arterial dilatation, presence of fistulous component, presence of venous outflow stenosis), treatment details (morbidity, mortality, pre/post modified Rankin scale (mRS) score), and follow-up details (mRS at last follow-up, time of follow-up, rupture during follow-up). AVM characteristics were obtained from review of digital subtraction angiographic images by the senior author and board-certified neuroradiologist. Patient demographics, treatment details and follow-up details were obtained from review of patient’s clinical records by various health care personnel and cross-checked for accuracy.
2.3. Outcomes The primary outcome of this study was AVM rupture. Risk of AVM rupture was then calculated from the entire cohort.
3.2. AVM characteristics There were 14 AVMs included in this study. Ten AVMs presented after with rupture, and four were discovered incidentally. Median (range) AVM nidus size was 10 (6–30) millimeters. The most common (7/14; 50%) AVM location was in the midbrain. Eleven (11/14; 79%) AVMs had associated aneurysms, either within the nidus, on a feeding artery, or both. All of these aneurysms were identified on pre-treatment, diagnostic DSA. Full AVM characteristics are summarized in Table 2.
3.3. Treatment characteristics Of the treated AVMs, 10 were treated after their initial presentation with symptomatic rupture and four were treated prophylactically. The most common treatment modality was SRS alone (6/14; 43%). Three patients were treated only with endovascular embolization, and the goal of embolization in these patients was to obliterate portions of the nidus and/or feeding arteries bearing aneurysms and reduce flow through the AVM. There was no treatment-related mortality, and treatment-related morbidity occurred in one patient (1/14; 7%). This patient experienced a stroke after endovascular embolization of the AVM but did not experience a change in his mRS score (pre/post mRS scores: 3/3). Seven (7/14; 50%) patients had a mRS score 0–1 at last followup; three of these patients (3/7; 43%) experienced rupture of their AVM during follow-up.
3.4. Risk of rupture in treated patients Treated patients (n = 14) were followed for a median (range) of 72 (7–264) months and a total of 101.6 patient-years. Five AVMs that had been treated ruptured during the follow-up period, and the annual risk of rupture after AVM treatment and no angiographically-documented complete obliteration was 4.9% per patient (95% CI: 1.6–11.5). Rupture occurred in two cases after SRS (after 103 and 130 months), in two cases after endovascular embolization (after 8 and 92 months), and in one case after surgery (after 97 months).
2.4. Statistical analysis Descriptive statistics were reported as a median and range for continuous variables or frequency and percentage for categorical variables. 95% confidence intervals (CI) for person-time rates were calculated with a Fisher’s exact test. Before running any statistical tests, the alpha (a) level was set at 0.05. All statistical analyses were performed using commercially available software (JMP 13, SAS, Inc.).
3. Results 3.1. Patient demographics 498 patients were diagnosed with an AVM at our institution during the study period and included in the AVM database. Of these patients, 14 patients had an AVM that was located within the brainstem and demonstrated post-treatment angiographically-documented residual nidus. Nine (9/14; 64%) patients were male. The median age (range) at AVM diagnosis was 48 (6–85) years. Most (10/14; 71%) patients presented after symptomatic AVM rupture, and headache was the most common presenting symptom (10/14; 77%). Full patient demographics are summarized in Table 1.
3.5. Characteristics of AVMs with hemorrhage at follow-up Of the five AVMs which ruptured after treatment, four (4/5; 80%) had originally presented with hemorrhage while one had been discovered incidentally. Intranidal and/or feeding artery aneurysms were present in 4/5 (80%) AVMs which ruptured at follow-up. One patient died as a result of the hemorrhage. The remaining four patients had mRS scores of 1, 1, 1, and 3, respectively, at last follow-up. Full treatment, follow-up, and rupture details of included patients are summarized in Table 3.
Table 1 PATIENT DEMOGRAPHICS. Key: AVM: arteriovenous malformation. VALUES INCLUDED PATIENTS MEDIAN AGE (RANGE) [YEARS]
14 48 (6–85)
MALE : FEMALE RATIO
1.8 : 1
SYMPTOMS AT PRESENTATION (n = 13)
HEADACHE FOCAL NEUROLOGICAL DEFICIT SEIZURES
10 (77%) 5 (38%) 1 (7.7%)
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Table 2 ARTERIOVENOUS MALFORMATION (AVM) CHARACTERISTICS. Key: AVM: arteriovenous malformation; PICA: posterior inferior cerebellar artery; A SP A: anterior spinal artery; PCA: posterior cerebral artery; SCA: superior cerebellar artery; AICA: anterior inferior cerebellar artery; BA: basilar artery; MRI: magnetic resonance imaging. VALUES AVMS MEDIAN SIZE (RANGE) [MM] TIME OF FIRST RUPTURE
AVM LOCATION
HEMORRHAGE LOCATION (n = 10)
FEEDING ARTERY
ANGIOARCHITECHTURAL FEATURES (n = 14)
14 10 (6–30) BEFORE INITIAL PRESENTATION DURING FOLLOW-UP MIDBRAIN PONS MEDULLA OBLONGATA INTRAVENTRICULAR SUBARACHNOID PARENCHYMAL PICA A SP A PCA SCA AICA BA PERFERATOR FEEDING ARTERY ANEURYSM INTRANIDAL ANEURYSM VENOUS VARIX MULTIPLE DRAINING VEINS VISIBLE ON MRI TERMINAL NIDUS EN PASSAGE NIDUS ARTERIAL DILATATION FISTULOUS COMPONENT VENOUS OUTFLOW STENOSIS
10 1 7 (50%) 4 (29%) 3 (21%) 3 5 6 3 2 7 1 1 5 5 8 2 3 7 7 8 6 1 6
4. Discussion In our cohort of 14 patients with a brainstem AVMs with residual nidus after treatment, we determined an annual risk of rupture of 4.9% per patient over a median of 72 months of follow-up. The most common treatment modality of these patients was SRSalone (n = 6), and two (33%) patients who underwent this treat-
ment later ruptured after 103 and 130 months. Of the five patients who ruptured after treatment, four (80%) had already ruptured once, and four (80%) had an intranidal and/or feeding artery aneurysm. These findings are important as they suggest that incomplete obliteration of a brainstem AVM still carries a high risk of future rupture (Figs. 1–3). A 2013 meta-analysis of 3,923 patients with cerebral AVMs and 18,423 patient-years of follow-up reported that the overall annual rate of hemorrhage was 3.0% (2.2% in unruptured AVMs and 4.5% in AVMs that had presented with hemorrhage) [2]. This meta-analysis also described that the natural history was less favorable for patients with prior hemorrhage, deep AVM location (brainstem, deep cerebellar, basal ganglia, thalamic, or callosal), exclusively deep venous drainage, and associated aneurysms. Of our included patients who ruptured after incomplete nidus obliteration during follow-up, 80% had prior hemorrhage and 80% had an associated intranidal or feeding artery aneurysm. Out observed risk of rupture (4.9% per patient-year) is not dissimilar to the expected rate of rupture of untreated AVMs. To date, there have been no large series on the natural history of brainstem AVMs alone, however, our results suggest that treatment resulting in incomplete nidus obliteration may not change the lesions’ natural history compared with conservative management, which deserves further investigation. Especially when considering the relatively high risks associated with surgery and/or endovascular embolization in this area and the relatively low rates of obliteration after SRS, AVMs selection for treatment should be very stringent to identify those that could reasonably be obliterated by treatment to justify the risks associated with intervention. In general, outcomes after treatment of brainstem AVMs is highly variable. In a series of 29 brainstem AVMs treated with only with microsurgery, Han et al. reports the highest rate of total obliteration in the literature (89.6%) [3]. In this study, a strategy of ‘‘in situ” obliteration of the AVM without nidus excision was proposed in order to decrease the morbidity of the procedure, and, based on their reported success, might be pursued in selected cases. In one of the landmark studies for the SRS treatment of brainstem AVMs, Massager et al. observed a three-year obliteration rate of just 73% in 87 patients [9]. However, this obliteration rate after SRS has yet to be surpassed in the literature with more recent series publishing total angiographic obliteration rates ranging from
Table 3 AVM TREATMENT, FOLLOW-UP, AND RUPTURE CHARACTERISTICS FOR INCLUDED PATIENTS. Key: SRS: stereotactic radiosurgery; mRS: modified Rankin scale; AVM: arteriovenous malformation. PATIENT
INITIAL HEMORRHAGE
INITIAL TREATMENT
TREATMENT MORBIDITY/ MORTALITY
FOLLOWUP RUPTURE
TIME TO RUPTURE (MONTHS)
RUPTURERELATED DEATH
INTRANIDAL OR FEEDING ARTERY ANEURYSM?
mRS SCORE AT LAST FOLLOW-UP
1 2 3
NO NO YES
NO/NO NO/NO NO/NO
NO YES NO
/ 130 /
/ NO /
FEEDING ARTERY INTRANIDAL INTRANIDAL
6 3 0
4 5 6 7 8 9 10 11 12 13 14
YES NO YES YES YES YES YES NO YES YES YES
Surgery SRS 1. Surgery 2. SRS Surgery SRS SRS Endovascular SRS Endovascular SRS SRS Surgery Endovascular 1. Endovascular 2. SRS
NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO YES/NO
NO NO YES NO NO YES NO NO YES YES NO
/ / 103 / / 92 / / 97 8 /
/ / NO / / NO / / NO YES /
INTRANIDAL FEEDING ARTERY / BOTH / BOTH INTRANIDAL / INTRANIDAL FEEDING ARTERY INTRANIDAL
3 0 1 6 2 1 1 1 1 6 3
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Fig. 1. 81 year old female who presented with severe headache secondary to pontine AVM rupture. A. Non-contrast CT shows dense subarachnoid hemorrhage isolated to the prepontine cistern. There was no supratentorial subarachnoid hemorrhage. B. Left vertebral artery cerebral angiogram demonstrates an arteriovenous malformation along the right lateral surface of the pons which is supplied by the right SCA and a hypertrophied perforator branch. There is a 4 mm distal feeding arterial aneurysm just proximal to the nidus which was the likely rupture point. The aneurysm was treated surgically. C. Post-operative angiogram shows resolution of the aneurysm but persistent AVM. The patient died following a mechanical fall in the setting of severe dementia nine years later.
Fig. 2. Patient with a history of stereotactic radiosurgery for treatment of a previously ruptured pontine AVM. Patient presented with left sided facial droop 103 months following treatment. A. Non-contrast CT shows a focus of hemorrhage in the region of the left facial nucleu. B. T2/MRI shows the AVM with hemosiderin and mild surrounding edema and the enlarged basilar artery perforator which supplied the AVM. C. Left vertebral artery angiogram shows a hypertrophied basilar artery perforator supplying the AVM. There was no feeding arterial or intranidal aneurysm.
44 to 70% [1,5,6,10–13]. Of these series that report incomplete nidus obliteration rates after treatment, there are limited data regarding the rate and risk of hemorrhage in these lesions specifically, which are increasingly encountered in daily practice. As diagnostic imaging paradigms have improved, specific AVM angioarchitectural features have been observed and characterized, and the presence of certain angioarchitectural features has even been shown to increase the risk of hemorrhage for these lesions [2]. In our study, 80% of patients who re-ruptured had a feeding arterial or intranidal aneurysm. These findings strengthen the idea that treatment strategies that specifically target these AVMassociated features, which represent angiographic weak points within AVM itself, might also be valuable therapeutic options for reducing the risk of hemorrhage [4,7,8]. Ultimately, the impact of
target embolization on the natural history of brainstem AVMs needs further study.
5. Limitations The greatest limitation of our retrospective, observational study is the small sample size, which reduces the power of our conclusions. Additionally, the included patients were very heterogenous regarding: treatment, ages, and follow-up time and/or protocol. Nevertheless, this study of a group of patients with an increasingly encountered problem (post-treatment incomplete nidus obliteration) and long-term follow-up provides valuable insights into the natural history of partially-treated brainstem AVMs.
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Sources of funding No funding was received for this research. Conflicting/competing interests The authors have no competing interests to declare. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.03.009. References
Fig. 3. 22 year old male who presented with a midbrain AVM rupture which was partially treated with surgery. A. Post-contrast T1 MRI shows the hematoma in the right paramedian midbrain. B. CT performed 97 months later demonstrates repeat hemorrhage in the same midbrain location, this time with intraventricular extension. Note the surgical clip from the prior surgery. C. Vertebral artery angiogram shows the AVM supplied primarily by the right PCA. There was a 1 mm intranidal aneurysm. D. The AVM was then treated with Gamma Knife. Repeat angiogram two years later showed resolution of the AVM.
6. Conclusions There is a real risk of AVM rupture/re-rupture after treatment results in incomplete nidus obliteration. Patients with brainstem AVMs who underwent treatment but still have a residual nidus should be counselled about the real risk of AVM rupture and be recommended to undergo close follow-up imaging studies to monitor the nidus. Further investigation regarding risk-factors for brainstem AVM rupture is warranted to better characterize and treat these challenging lesions. Acknowledgements The authors have no acknowledgements.
[1] Choi HJ, Choi SK, Lim YJ. Radiosurgical techniques and clinical outcomes of gamma knife radiosurgery for brainstem arteriovenous malformations. J Korean Neurosurg Soc 2012;52:534–40. [2] Gross BA, Du R. Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg 2013;118:437–43. [3] Han SJ, Englot DJ, Kim H, Lawton MT. Brainstem arteriovenous malformations: anatomical subtypes, assessment of ‘‘occlusion in situ” technique, and microsurgical results. J Neurosurg 2015;122:107–17. [4] Jha V, Behari S, Jaiswal AK, Bhaisora KS, Shende YP, Phadke RV. The ‘‘focus on aneurysm” principle: Classification and surgical principles of management of concurrent arterial aneurysm with arteriovenous malformation causing intracranial hemorrhage. Asian J Neurosurg 2016;11:240–54. [5] Kano H, Kondziolka D, Flickinger JC, Yang HC, Flannery TJ, Niranjan A, et al. Stereotactic radiosurgery for arteriovenous malformations, Part 5: management of brainstem arteriovenous malformations. J Neurosurg 2012;116:44–53. [6] Koga T, Shin M, Terahara A, Saito N. Outcomes of radiosurgery for brainstem arteriovenous malformations. Neurosurgery 2011;69:45–51. [7] Lv X, Wu Z, Li Y, Yang X, Jiang C, Sun Y, et al. Endovascular treatment of cerebral aneurysms associated with arteriovenous malformations. Eur J Radiol 2012;81:1296–8. [8] Marks MP, Lane B, Steinberg GK, Snipes GJ. Intranidal aneurysms in cerebral arteriovenous malformations: evaluation and endovascular treatment. Radiology 1992;183:355–60. [9] Massager N, Regis J, Kondziolka D, Njee T, Levivier M. Gamma knife radiosurgery for brainstem arteriovenous malformations: preliminary results. J Neurosurg 2000;93(Suppl 3):102–3. [10] Nagy G, Major O, Rowe JG, Radatz MW, Hodgson TJ, Coley SC, et al. Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions. Neurosurgery 2012;70:1458–69. discussion 1469-1471. [11] Pollock BE, Gorman DA, Brown PD. Radiosurgery for arteriovenous malformations of the basal ganglia, thalamus, and brainstem. J Neurosurg 2004;100:210–4. [12] Yang W, Porras JL, Garzon-Muvdi T, Xu R, Caplan JM, Hung AL, et al. Management outcome of brainstem arteriovenous malformations: the role of radiosurgery. World Neurosurg 2016;94:64–72. [13] Yen CP, Steiner L. Gamma knife surgery for brainstem arteriovenous malformations. World Neurosurg 2011;76:87–95.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical study
Clinical outcome of brainstem arteriovenous malformations after incomplete nidus obliteration Thomas J. Sorenson a,b, Giuseppe Lanzino b,d, Kelly D. Flemming c, Deena M. Nasr c, Shannon Y. Chiu c, Bruce E. Pollock b, Waleed Brinjikji b,d,⇑ a
School of Medicine, University of Minnesota, Minneapolis, MN, USA Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA Department of Neurology, Mayo Clinic, Rochester, MN, USA d Department of Radiology, Mayo Clinic, Rochester, MN, USA b c
a r t i c l e
i n f o
Article history: Received 21 January 2019 Accepted 8 March 2019
Keywords: Brainstem Arteriovenous malformation Stereotactic radiosurgery Clinical outcome Rupture
a b s t r a c t Purpose: Brainstem arteriovenous malformations (AVMs) present a formidable therapeutic challenge, and a variety of surgical and non-surgical treatment strategies can be used to obliterate the AVM nidus, eliminating its risk of hemorrhage. However, complete obliteration of brainstem AVMs is often not possible. We aimed to investigate the natural history of brainstem AVMs with incomplete nidus obliteration after initial treatment. Methods: Data from consecutive patients who presented to our institution during the study period with a brainstem AVM and residual nidus after treatment were retrospectively reviewed. We evaluated patients for the incidence of AVM rupture and calculated the risk of rupture after treatment resulted in incomplete nidus obliteration. Results: A total of 14 patients were included, five of whom suffered rupture after incomplete nidus obliteration (36%). Annual risk of rupture was 4.9% (95% CI: 1.60–11.5) per patient over a median follow-up of 72 months. The most common treatment modality of these patients was SRS-alone (n = 6), and two (33%) patients who underwent this treatment later ruptured after 103 and 130 months. Of the five patients who ruptured after treatment, 80% had already ruptured once, and 80% had an intranidal and/or feeding artery aneurysm. Conclusions: Brainstem AVMs with incomplete nidus obliteration are at high risk of future rupture. Patients with brainstem AVMs who have a residual nidus after treatment should be counselled about the risk of AVM rupture and be recommended to undergo close follow-up imaging studies to monitor the nidus. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Brainstem arteriovenous malformations (AVMs) are uncommon lesions and present a formidable therapeutic challenge due to their location in eloquent brain. A variety of surgical and non-surgical treatment strategies (i.e. stereotactic radiosurgery [SRS], endovascular embolization) can be used alone or in tandem to obliterate the AVM nidus and eliminate its risk of rupture. However, complete obliteration of brainstem AVMs is often not possible due to the risk of injuring critical neurological structures, and these treatment strategies not infrequently result in incomplete obliteration of the
AVM nidus [1,9,12,13], which may then still be prone to rupture. In our consecutive series of patients with brainstem AVMs with residual nidus after treatment, we aimed to investigate the risk of rupture after incomplete nidus obliteration of a brainstem AVM. 2. Materials and methods This study was approved by our Institutional Review Board and consent was obtained to use clinical information for research purposes. 2.1. Patient identification
⇑ Corresponding author at: Department of Radiology, Neurologic Surgery, 200 1st Street SW, Rochester, MN 55902, USA. E-mail address: [email protected] (W. Brinjikji). https://doi.org/10.1016/j.jocn.2019.03.009 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
We reviewed an author-maintained database of consecutive patients who were diagnosed and/or treated for an AVM at our
67
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institution between January 1, 2000 and July 1, 2018 to identify patients with an AVM nidus located in the brainstem (medulla oblongata, pons, or midbrain). Patients were included in our study if they: (1) agreed to have their information used for research purposes, (2) were evaluated and treated for a brainstem AVM, and (3) had angiographically-confirmed residual nidus after treatment. Post-treatment angiography was performed immediately postoperatively and then against after three years in all included patients. Additional angiographic and/or clinical follow-up was individualized based on patient and AVM characteristics. Patients were excluded if: (1) the location of their AVM nidus was not within the brainstem, (2) their AVM was not treated, or (3) their AVM had angiographically-documented complete nidus obliteration after treatment.
2.2. Data collection Data were collected based on clinical and radiographic chart review. Collected data included: patient demographics (sex, age), AVM characteristics (size, location, feeding arteries, hemorrhage status, hemorrhage location, involved lesion tissue, feeding artery, feeding artery/intranidal aneurysm, presence of venous varix, presence of multiple draining veins, visibility on MRI, terminal or en passage nidus, presence of arterial dilatation, presence of fistulous component, presence of venous outflow stenosis), treatment details (morbidity, mortality, pre/post modified Rankin scale (mRS) score), and follow-up details (mRS at last follow-up, time of follow-up, rupture during follow-up). AVM characteristics were obtained from review of digital subtraction angiographic images by the senior author and board-certified neuroradiologist. Patient demographics, treatment details and follow-up details were obtained from review of patient’s clinical records by various health care personnel and cross-checked for accuracy.
2.3. Outcomes The primary outcome of this study was AVM rupture. Risk of AVM rupture was then calculated from the entire cohort.
3.2. AVM characteristics There were 14 AVMs included in this study. Ten AVMs presented after with rupture, and four were discovered incidentally. Median (range) AVM nidus size was 10 (6–30) millimeters. The most common (7/14; 50%) AVM location was in the midbrain. Eleven (11/14; 79%) AVMs had associated aneurysms, either within the nidus, on a feeding artery, or both. All of these aneurysms were identified on pre-treatment, diagnostic DSA. Full AVM characteristics are summarized in Table 2.
3.3. Treatment characteristics Of the treated AVMs, 10 were treated after their initial presentation with symptomatic rupture and four were treated prophylactically. The most common treatment modality was SRS alone (6/14; 43%). Three patients were treated only with endovascular embolization, and the goal of embolization in these patients was to obliterate portions of the nidus and/or feeding arteries bearing aneurysms and reduce flow through the AVM. There was no treatment-related mortality, and treatment-related morbidity occurred in one patient (1/14; 7%). This patient experienced a stroke after endovascular embolization of the AVM but did not experience a change in his mRS score (pre/post mRS scores: 3/3). Seven (7/14; 50%) patients had a mRS score 0–1 at last followup; three of these patients (3/7; 43%) experienced rupture of their AVM during follow-up.
3.4. Risk of rupture in treated patients Treated patients (n = 14) were followed for a median (range) of 72 (7–264) months and a total of 101.6 patient-years. Five AVMs that had been treated ruptured during the follow-up period, and the annual risk of rupture after AVM treatment and no angiographically-documented complete obliteration was 4.9% per patient (95% CI: 1.6–11.5). Rupture occurred in two cases after SRS (after 103 and 130 months), in two cases after endovascular embolization (after 8 and 92 months), and in one case after surgery (after 97 months).
2.4. Statistical analysis Descriptive statistics were reported as a median and range for continuous variables or frequency and percentage for categorical variables. 95% confidence intervals (CI) for person-time rates were calculated with a Fisher’s exact test. Before running any statistical tests, the alpha (a) level was set at 0.05. All statistical analyses were performed using commercially available software (JMP 13, SAS, Inc.).
3. Results 3.1. Patient demographics 498 patients were diagnosed with an AVM at our institution during the study period and included in the AVM database. Of these patients, 14 patients had an AVM that was located within the brainstem and demonstrated post-treatment angiographically-documented residual nidus. Nine (9/14; 64%) patients were male. The median age (range) at AVM diagnosis was 48 (6–85) years. Most (10/14; 71%) patients presented after symptomatic AVM rupture, and headache was the most common presenting symptom (10/14; 77%). Full patient demographics are summarized in Table 1.
3.5. Characteristics of AVMs with hemorrhage at follow-up Of the five AVMs which ruptured after treatment, four (4/5; 80%) had originally presented with hemorrhage while one had been discovered incidentally. Intranidal and/or feeding artery aneurysms were present in 4/5 (80%) AVMs which ruptured at follow-up. One patient died as a result of the hemorrhage. The remaining four patients had mRS scores of 1, 1, 1, and 3, respectively, at last follow-up. Full treatment, follow-up, and rupture details of included patients are summarized in Table 3.
Table 1 PATIENT DEMOGRAPHICS. Key: AVM: arteriovenous malformation. VALUES INCLUDED PATIENTS MEDIAN AGE (RANGE) [YEARS]
14 48 (6–85)
MALE : FEMALE RATIO
1.8 : 1
SYMPTOMS AT PRESENTATION (n = 13)
HEADACHE FOCAL NEUROLOGICAL DEFICIT SEIZURES
10 (77%) 5 (38%) 1 (7.7%)
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Table 2 ARTERIOVENOUS MALFORMATION (AVM) CHARACTERISTICS. Key: AVM: arteriovenous malformation; PICA: posterior inferior cerebellar artery; A SP A: anterior spinal artery; PCA: posterior cerebral artery; SCA: superior cerebellar artery; AICA: anterior inferior cerebellar artery; BA: basilar artery; MRI: magnetic resonance imaging. VALUES AVMS MEDIAN SIZE (RANGE) [MM] TIME OF FIRST RUPTURE
AVM LOCATION
HEMORRHAGE LOCATION (n = 10)
FEEDING ARTERY
ANGIOARCHITECHTURAL FEATURES (n = 14)
14 10 (6–30) BEFORE INITIAL PRESENTATION DURING FOLLOW-UP MIDBRAIN PONS MEDULLA OBLONGATA INTRAVENTRICULAR SUBARACHNOID PARENCHYMAL PICA A SP A PCA SCA AICA BA PERFERATOR FEEDING ARTERY ANEURYSM INTRANIDAL ANEURYSM VENOUS VARIX MULTIPLE DRAINING VEINS VISIBLE ON MRI TERMINAL NIDUS EN PASSAGE NIDUS ARTERIAL DILATATION FISTULOUS COMPONENT VENOUS OUTFLOW STENOSIS
10 1 7 (50%) 4 (29%) 3 (21%) 3 5 6 3 2 7 1 1 5 5 8 2 3 7 7 8 6 1 6
4. Discussion In our cohort of 14 patients with a brainstem AVMs with residual nidus after treatment, we determined an annual risk of rupture of 4.9% per patient over a median of 72 months of follow-up. The most common treatment modality of these patients was SRSalone (n = 6), and two (33%) patients who underwent this treat-
ment later ruptured after 103 and 130 months. Of the five patients who ruptured after treatment, four (80%) had already ruptured once, and four (80%) had an intranidal and/or feeding artery aneurysm. These findings are important as they suggest that incomplete obliteration of a brainstem AVM still carries a high risk of future rupture (Figs. 1–3). A 2013 meta-analysis of 3,923 patients with cerebral AVMs and 18,423 patient-years of follow-up reported that the overall annual rate of hemorrhage was 3.0% (2.2% in unruptured AVMs and 4.5% in AVMs that had presented with hemorrhage) [2]. This meta-analysis also described that the natural history was less favorable for patients with prior hemorrhage, deep AVM location (brainstem, deep cerebellar, basal ganglia, thalamic, or callosal), exclusively deep venous drainage, and associated aneurysms. Of our included patients who ruptured after incomplete nidus obliteration during follow-up, 80% had prior hemorrhage and 80% had an associated intranidal or feeding artery aneurysm. Out observed risk of rupture (4.9% per patient-year) is not dissimilar to the expected rate of rupture of untreated AVMs. To date, there have been no large series on the natural history of brainstem AVMs alone, however, our results suggest that treatment resulting in incomplete nidus obliteration may not change the lesions’ natural history compared with conservative management, which deserves further investigation. Especially when considering the relatively high risks associated with surgery and/or endovascular embolization in this area and the relatively low rates of obliteration after SRS, AVMs selection for treatment should be very stringent to identify those that could reasonably be obliterated by treatment to justify the risks associated with intervention. In general, outcomes after treatment of brainstem AVMs is highly variable. In a series of 29 brainstem AVMs treated with only with microsurgery, Han et al. reports the highest rate of total obliteration in the literature (89.6%) [3]. In this study, a strategy of ‘‘in situ” obliteration of the AVM without nidus excision was proposed in order to decrease the morbidity of the procedure, and, based on their reported success, might be pursued in selected cases. In one of the landmark studies for the SRS treatment of brainstem AVMs, Massager et al. observed a three-year obliteration rate of just 73% in 87 patients [9]. However, this obliteration rate after SRS has yet to be surpassed in the literature with more recent series publishing total angiographic obliteration rates ranging from
Table 3 AVM TREATMENT, FOLLOW-UP, AND RUPTURE CHARACTERISTICS FOR INCLUDED PATIENTS. Key: SRS: stereotactic radiosurgery; mRS: modified Rankin scale; AVM: arteriovenous malformation. PATIENT
INITIAL HEMORRHAGE
INITIAL TREATMENT
TREATMENT MORBIDITY/ MORTALITY
FOLLOWUP RUPTURE
TIME TO RUPTURE (MONTHS)
RUPTURERELATED DEATH
INTRANIDAL OR FEEDING ARTERY ANEURYSM?
mRS SCORE AT LAST FOLLOW-UP
1 2 3
NO NO YES
NO/NO NO/NO NO/NO
NO YES NO
/ 130 /
/ NO /
FEEDING ARTERY INTRANIDAL INTRANIDAL
6 3 0
4 5 6 7 8 9 10 11 12 13 14
YES NO YES YES YES YES YES NO YES YES YES
Surgery SRS 1. Surgery 2. SRS Surgery SRS SRS Endovascular SRS Endovascular SRS SRS Surgery Endovascular 1. Endovascular 2. SRS
NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO NO/NO YES/NO
NO NO YES NO NO YES NO NO YES YES NO
/ / 103 / / 92 / / 97 8 /
/ / NO / / NO / / NO YES /
INTRANIDAL FEEDING ARTERY / BOTH / BOTH INTRANIDAL / INTRANIDAL FEEDING ARTERY INTRANIDAL
3 0 1 6 2 1 1 1 1 6 3
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Fig. 1. 81 year old female who presented with severe headache secondary to pontine AVM rupture. A. Non-contrast CT shows dense subarachnoid hemorrhage isolated to the prepontine cistern. There was no supratentorial subarachnoid hemorrhage. B. Left vertebral artery cerebral angiogram demonstrates an arteriovenous malformation along the right lateral surface of the pons which is supplied by the right SCA and a hypertrophied perforator branch. There is a 4 mm distal feeding arterial aneurysm just proximal to the nidus which was the likely rupture point. The aneurysm was treated surgically. C. Post-operative angiogram shows resolution of the aneurysm but persistent AVM. The patient died following a mechanical fall in the setting of severe dementia nine years later.
Fig. 2. Patient with a history of stereotactic radiosurgery for treatment of a previously ruptured pontine AVM. Patient presented with left sided facial droop 103 months following treatment. A. Non-contrast CT shows a focus of hemorrhage in the region of the left facial nucleu. B. T2/MRI shows the AVM with hemosiderin and mild surrounding edema and the enlarged basilar artery perforator which supplied the AVM. C. Left vertebral artery angiogram shows a hypertrophied basilar artery perforator supplying the AVM. There was no feeding arterial or intranidal aneurysm.
44 to 70% [1,5,6,10–13]. Of these series that report incomplete nidus obliteration rates after treatment, there are limited data regarding the rate and risk of hemorrhage in these lesions specifically, which are increasingly encountered in daily practice. As diagnostic imaging paradigms have improved, specific AVM angioarchitectural features have been observed and characterized, and the presence of certain angioarchitectural features has even been shown to increase the risk of hemorrhage for these lesions [2]. In our study, 80% of patients who re-ruptured had a feeding arterial or intranidal aneurysm. These findings strengthen the idea that treatment strategies that specifically target these AVMassociated features, which represent angiographic weak points within AVM itself, might also be valuable therapeutic options for reducing the risk of hemorrhage [4,7,8]. Ultimately, the impact of
target embolization on the natural history of brainstem AVMs needs further study.
5. Limitations The greatest limitation of our retrospective, observational study is the small sample size, which reduces the power of our conclusions. Additionally, the included patients were very heterogenous regarding: treatment, ages, and follow-up time and/or protocol. Nevertheless, this study of a group of patients with an increasingly encountered problem (post-treatment incomplete nidus obliteration) and long-term follow-up provides valuable insights into the natural history of partially-treated brainstem AVMs.
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Sources of funding No funding was received for this research. Conflicting/competing interests The authors have no competing interests to declare. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.03.009. References
Fig. 3. 22 year old male who presented with a midbrain AVM rupture which was partially treated with surgery. A. Post-contrast T1 MRI shows the hematoma in the right paramedian midbrain. B. CT performed 97 months later demonstrates repeat hemorrhage in the same midbrain location, this time with intraventricular extension. Note the surgical clip from the prior surgery. C. Vertebral artery angiogram shows the AVM supplied primarily by the right PCA. There was a 1 mm intranidal aneurysm. D. The AVM was then treated with Gamma Knife. Repeat angiogram two years later showed resolution of the AVM.
6. Conclusions There is a real risk of AVM rupture/re-rupture after treatment results in incomplete nidus obliteration. Patients with brainstem AVMs who underwent treatment but still have a residual nidus should be counselled about the real risk of AVM rupture and be recommended to undergo close follow-up imaging studies to monitor the nidus. Further investigation regarding risk-factors for brainstem AVM rupture is warranted to better characterize and treat these challenging lesions. Acknowledgements The authors have no acknowledgements.
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