Accepted Manuscript Management of arteriovenous malformations associated with developmental venous anomalies: A literature review and report of two cases Michael Zhang, MD, Ian D. Connolly, MS, Mario K. Teo, MD, George Yang, MD, Robert Dodd, MD, PhD, Michael Marks, MD, Mario Zuccarello, MD, Gary K. Steinberg, MD, PhD PII: S1878-8750(17)31142-7 DOI: 10.1016/j.wneu.2017.07.042 Reference: WNEU 6104 To appear in: World Neurosurgery Received Date: 18 April 2017 Revised Date: 7 July 2017 Accepted Date: 11 July 2017 Please cite this article as: Zhang M, Connolly ID, Teo MK, Yang G, Dodd R, Marks M, Zuccarello M, Steinberg GK, Management of arteriovenous malformations associated with developmental venous anomalies: A literature review and report of two cases, World Neurosurgery (2017), doi: 10.1016/ j.wneu.2017.07.042. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Zhang ACCEPTED MANUSCRIPT Management of arteriovenous malformations associated with developmental venous anomalies: A literature review and report of two cases Michael Zhanga, Ian D. Connollya, Mario K Teoa,b, George Yangc, Robert Dodda, Michael RI PT Marksa, Mario Zuccarelloc, Gary K Steinberga a. Department of Neurosurgery and Stanford Stroke Center, Stanford University Medical SC Center, Stanford, California, USA b. Department of Neurosurgery, Bristol Institute of Clinical Neuroscience, North Bristol M AN U University Hospital, UK c. Department of Neurosurgery, Mayfield Brain & Spine, Cincinnati, Ohio, USA TE D Corresponding Author Gary K. Steinberg, MD, PhD Stanford University School of Medicine EP 300 Pasteur Drive (R281) AC C Stanford, CA 94305-5327 Tel: 650-725-5562 Fax: 650-723-2815 Email: gsteinberg@stanford.edu Highest Academic Degrees Michael Zhang, MD Ian D Connolly, MS Mario K Teo, MD 1 Zhang ACCEPTED MANUSCRIPT George Yang, MD Robert Dodd, MD, PhD Michael Marks, MD Mario Zuccarello, MD RI PT Gary K Steinberg, MD, PhD1 Key Words SC Arteriovenous malformations, co-existing malformations, CyberKnife radiosurgery, radiosurgery Abbreviations List AVM: Arteriovenous malformation TE D DVA: Developmental venous anomaly M AN U developmental venous anomaly, glue embolization, multimodal treatment, stereotactic MCA: Middle cerebral artery PCA: Posterior cerebral artery EP SSS: Superior sagittal sinus AC C SRS: Stereotactic radiosurgery CKS: CyberKnife surgery *table abbreviations listed separately Author Email Addresses zhangm@stanford.edu (M. Zhang) iancon16@stanford.edu (IDC) 2 Zhang ACCEPTED MANUSCRIPT marioteo@gmail.com (MKT) yangge@ucmail.uc.edu (GY) robdodd@stanford.edu (RD) mzuccarello@mayfieldclinic.com (M. Zuccarello) AC C EP TE D M AN U SC steinberg@stanford.edu (GKS) RI PT marks1@stanford.edu (MM) 3 Zhang ACCEPTED MANUSCRIPT ABSTRACT Objective: Cerebrovascular malformation classification has revealed intermediary lesions that warrant further review due to their unusual presentation and management. We present RI PT two cases of arteriovenous malformations (AVMs) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies. SC Methods: Two cases of AVMs associated with DVA were identified and a literature search clinical features were documented. Results: M AN U for published cases between 1980 and 2016 was conducted. Patient demographics and Case 1: A 29-year-old female presenting with parenchymal hemorrhage and left TE D homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral and posterior cerebral arteries, with major venous drainage EP to the superior sagittal sinus (SSS). AC C Case 2: A 34-year-old female evaluated for night tremors and incontinence had subsequent imaging that revealed a left parietal AVM with venous drainage to the SSS. Including ours, 22 cases of coexisting AVMs and DVAs are described in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7, embolization in 6, surgical resection in 4, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12/18). 4 Zhang ACCEPTED MANUSCRIPT Conclusions: Patients with coexisting AVMs and DVAs tend to have hemorrhagic presentation. Contrary to traditional AVM management, it is important to preserve the draining vein via the DVA to achieving safe AVM obliteration. AC C EP TE D M AN U Highlights: included in a separate document SC RI PT ensure the safe, sustained circulatory outflow of the associated brain parenchyma, while 5 Zhang ACCEPTED MANUSCRIPT INTRODUCTION Arteriovenous malformation (AVM), capillary telangiectasia, cavernous malformation, and developmental venous anomaly (DVA) represent the 4 commonly recognized subgroups of RI PT cerebrovascular malformations.1 The incidence of AVM has been estimated by a variety of population-based studies and is generally cited as around 1 in 100,000.2 An AVM occurs when a collection of arteries and veins form without an intervening capillary bed. This results M AN U presentation of hemorrhage at an annual rate of 2–3%.2–5 SC in the high-pressure shunting of blood thought to be responsible for the symptomatic By comparison, a DVA usually appears as a collection of radiating veins converging on a large and centrally-located draining vein. This is classically described as having a fan-shaped “caput medusae” appearance, although this is not always seen.6 Histologically, the DVA TE D consists of a collection of thickened and hyalinized veins with little smooth muscle and elastic tissue.1 They are the most common cerebrovascular abnormality, with an overall incidence of 2% to 4%, 7–12 and thus are much more common than AVMs. However, DVAs, EP usually discovered incidentally, rarely if ever bleed, and the reported annual bleeding rates of AC C 0.2%–0.3% is likely due to bleeding from coexisting cavernous malformations.13,14 Despite their contrasting properties, convergence of an AVM and DVA presents a tenuous hemodynamic balance that warrants neurosurgical intervention. Presumably, when the DVA’s low resistance drainage system receives a high-pressure inflow, the bleeding risk is greater than from either entity alone. Perhaps the additional strain to the hemodynamic balance from increased inflow leads to the commonly reported symptoms of coexisting AVMs and DVAs, such as headache, seizures, and neurological deficits.15 6 Zhang ACCEPTED MANUSCRIPT Given the ongoing need to understand the clinical manifestation and management of these colocalizing cerebrovascular malformations, we present 2 cases of an AVM associated with a DVA from our institutions. Huang and colleagues reported the first case of a coexisting AVM RI PT and DVA in 1984.16 To aid in the treatment of future identified cases, we also review the decision-making and outcomes from published literature for this rare transitional SC malformation. M AN U MATERIALS AND METHODS We identified cases of AVM associated with DVA from a locally-held institutional database at Stanford University. A literature search was also conducted for published cases between 1980 and 2016 by authors MZ and IDC using the PubMed database in order to identify case TE D reports of this unique entity. The following terms were used: arteriovenous malformation and developmental venous anomaly, AVM and DVA, venous angioma and AVM, venous malformation and AVM, and associated DVA. We also reviewed the references of these EP journal articles for additional reports. Authors MZ, MKT and IDC reviewed and extracted AC C data from the studies. Clarification of information from the literature was sought from senior authors where appropriate. Patient demographics and clinical features were examined, including clinical and radiographic presentation and outcomes, feeding artery distribution, AVM location, draining vein termination site, and treatment modality. Univariate analyses were performed with the statistical software Stata® (StataCorp LLC, Texas, USA), using the appropriate tests; a pvalue < 0.05 was considered statistically significant. 7 Zhang ACCEPTED MANUSCRIPT RESULTS Patient 1 RI PT A 29-year-old female who suffered from an intracerebral hemorrhage presented with an episode of right-sided headache and partial left homonymous hemianopsia. CT and MRI scans of the brain demonstrated rupture of the right parieto-occipital AVM component. SC Angiography demonstrated a 3.5 cm Spetzler-Martin grade IV mixed AVM fed from the right anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral M AN U artery (PCA) with primary venous drainage into a high flow DVA. Functional MRI demonstrated the AVM did not involve the calcarine or motor cortices and MR tractography confirmed the AVM nidus was located adjacent to but not intimately involving the corticospinal and geniculocalcarine tracts (Figure 1). Despite the high-grade lesion, in view TE D of the ruptured history, the decision was made to proceed with staged multimodal treatment. The first stage involved embolization of the two pericallosal artery pedicles, resulting in angiographic occlusion of a third of the AVM nidus. After the embolization, a decision was EP made to pursue radiosurgery instead of microsurgery due to the size and eloquence of the AC C AVM. A second angiogram 2 months later demonstrated interval (asymptomatic) occlusion of the right ACA supply to the AVM. The patient was treated with single fraction frameless stereotactic radiosurgery (SRS) 10 months after presentation and tolerated the procedure without difficulty. At last follow-up (18 months since presentation), she reported decreased frequency and severity of headaches with improvement in visual symptoms. MRI and MRA also showed reduction in the AVM nidus with preservation of the DVA. Patient 2 8 Zhang ACCEPTED MANUSCRIPT A 34-year-old right-handed female initially presented to an outside hospital with hemisensory changes and weakness. CT and MRI imaging of the brain showed a left parietal occipital AVM. Embolization was attempted but determined not to be safe. The patient was seen at Stanford Health Care 2 months later, where her husband reported a right arm jerking RI PT movement during sleep and nocturnal incontinence, which was concerning for seizures. An angiogram showed an extremely diffuse high-flow, Spetzler-Martin grade III AVM approximately 4 cm in diameter associated with a large DVA. It was supplied by multiple SC enlarged branches from the left MCA and PCA, with terminal drainage into the SSS (Figure 2). Embolization was again attempted but not completed due to the diffuse vasculature. The M AN U AVM component was eventually treated via partial resection of several of the AVM feeders with adjuvant CyberKnife radiosurgery (CKS), being careful to leave the DVA component undisturbed. After surgery, the patient’s hemisensory changes, weakness, and seizures resolved. After 14 months of follow-up, the patient was neurologically normal and remains Previous reports TE D seizure free. EP Including our cases, 22 cases of coexisting AVM and DVA have been described in the literature. Clinical and demographic data for all reported cases are summarized in Table AC C 1.6,16–27 The mean patient age was 30 years of age and 12 (55%) were male. The mean follow up was 30 months (range 4 – 161 months). Fifteen (68%) of the reported cases presented with hemorrhage, and among cases detailing the radiographical site of bleeding, all were localized to the AVM component. There was no significant difference in age by gender or event of hemorrhage. There were 8/12 (66.6%) of cases with superficial venous drainage compared with 6/8 (75%) with deep venous drainage that reported hemorrhagic presentation (p=0.54, Fisher’s exact test). Therefore the venous drainage pattern and hemorrhagic risk is 9 Zhang ACCEPTED MANUSCRIPT comparable. Among reports with complete documentation of clinical presentation (n = 17), 65% experienced new onset weakness. Loss of consciousness (13.6%) and seizures (10%) were RI PT less frequently described. Radiographically, the site of AVM was distributed in the parietal, frontal, cerebellar and temporal territories in 32%, 32%, 23%, and 18%, respectively. Meanwhile, feeding arteries were identified in the MCA, ACA, and posterior circulation in SC 36%, 45%, and 27% of imaging, respectively. Only 1 case described an associated intranidal M AN U aneurysm.6 The most broadly utilized treatment modality was radiosurgery, which was performed in 7 (32%) cases18,21,22,25,27 1 of which required multiple ablations.22 This was followed by embolization in 6 (27%)6,17,19,24 and resection in 4 (18%)16,20,23,26 cases. Radiosurgical TE D management was utilized as an adjuvant therapy in 4 (18%) cases6,25. For patients who underwent embolization, 1 (5%) was part of preoperative treatments.25 In 3 (33%) cases, multiple embolizations were required.6,19 A multimodal approach was performed in 5 (23%) EP cases.6,25 Three (14%) cases underwent embolization with adjuvant radiosurgery.6,25 The AC C other 2 cases incorporated AVM resection, 1 with preoperative embolization25 and 1 with adjuvant CKS. Among those with adequate follow up information, 89% (16/18) had stable or improved clinical outcomes. Two patients experienced hemorrhagic complications post treatment (1 experienced hemorrhagic infarction postoperatively, another patient had AVM rupture after radiation treatment). Among those patients with good outcomes, 75% (12/16) demonstrated complete obliteration of their AVM; 4 through the use of embolization and 5 through the use 10 Zhang ACCEPTED MANUSCRIPT of radiosurgery. Of the 4 previous reports that did not describe total obliteration, only 2 detailed radiographic outcomes. One patient was initially followed conservatively. This resulted in resolution of symptoms until the appearance of a new AVM, which was treated with embolization at a different site 10 years later.24 Another case that had initially identified RI PT a CVM by histopathology exhibited AVM properties on subsequent follow-up and resection.26 SC DISCUSSION M AN U As shown in our summary of the published series of co-existing AVMs and DVAs, 68% (95% CI: 49%- 88%) of the reported cases presented with hemorrhage, often with associated motor deficits, thus highlighting the high risk nature of these lesions. This hemorrhagic prevalence is higher than the 38% identified in the traditional AVM population.28 The TE D reported transient neurologic deficits, seizures, or loss of consciousness in the remaining patients further demonstrates the maladaptive perfusion in these transitional lesions. Given these concerning presentations, a better understanding of the elevated hemodynamic and EP surgical risks accompanying these co-existing lesions will enable prompt primary and AC C secondary prevention of further hemorrhage. The presence of a DVA in these transitions lesions introduces a tenuous and slow-adapting terminal angioarchitecture that could lead to suboptimal venous drainage. It is possible that these weaker vessels display a decreased responsiveness to flow changes both in the short and long term. Prior work has shown that in the absence of an AVM-associated aneurysm, features including deep venous drainage, deep AVM location, draining vein stenosis and a single solitary draining vein are at an elevated risk of hemorrhage.5,29 Meanwhile, DVAs may 11 Zhang ACCEPTED MANUSCRIPT persist well after their arterial feeders have been obliterated and enable recrudescence of the disease.24,26 Despite the risk imposed by the aberrant drainage, successful neurosurgical management of RI PT these transitional lesions should target the AVM component, leaving behind a tissue- dependent DVA with low-hemorrhagic risk. Moreover, preservation of the DVA is crucial to maintain parenchymal perfusion, as damage to the DVA would lead to catastrophic venous SC infarction.7 As noted in our literature review, the few cases with negative outcomes involved obliteration of both AVM and DVA components, leading to venous hemorrhagic infarction M AN U and recurrent AVM hemorrhage. Early experience was reported by Lindquist and colleagues in 1993, who performed gamma knife surgery to both an AVM and DVA after a hemorrhagic presentation; it resulted in the patient’s death at 28 months following irradiation, due to rebleeding likely secondary to delayed obliteration of the DVA component.22 Two other TE D cases with DVA surgical obliteration due to inadvertent injury and intraoperative bleeding also resulted in poor patient outcomes.23,25 In 2000, Aksoy and colleagues performed radiosurgery to both the AVM and DVA, and reported a good patient outcome at the 6-month EP follow-up.18 However, as the radiation effect is generally delayed at 2–4 years, it remains AC C speculative if the patient remained well at longer term follow-up. While final treatment planning should be patient and provider-specific, our review of the literature shows that interventions for co-localizing AVMs and DVAs have a reliably positive effect on their angioarchitecture and hemodynamics. Modalities for AVM-DVA treatment have included a combination of surgical resection, radiosurgery, and embolization, with an overall complete obliteration of 67% (12/18) in those with adequate follow-up information. This number is comparable to the 50%–80% reported in prior cohort analyses of solitary 12 Zhang ACCEPTED MANUSCRIPT AVMs treated by radiosurgery and embolization.30–34 Further restricting this analysis to identifying those lesions with only treatment to the AVM-component would likely show an even better response to intervention. As far as which modality may encourage complete obliteration, AVM inflow can be significantly decreased by either embolization or RI PT radiosurgery; it is worthwhile to note that among patients with partial obliteration, 2 had received radiosurgery alone18,22 and 2 had received radiosurgery as adjuncts to embolization.6, 35–37 The remaining case, noted to be a difficult embolization procedure, was SC deferred upon initial evaluation.19 This observed trend towards incomplete obliteration following primary or adjuvant-radiosurgery mirrors that seen in the traditional AVM M AN U literature, and may help guide future decisions on the selection of multimodal interventions for mixed lesions.31,32,36 Small numbers and variable quality of the reported cases from the literature are among the TE D limitations of this study. The rate of hemorrhage in the AVM-DVA joint entity could be an overestimate in view of the inevitable selection and publication biases of such reports. While it would be ideal to analyze the cases and adjust for confounding variables, such as AVM EP nidus size, random error and variations can be significant in such small samples. It would be AC C important to perform cerebral angiographic studies to make the distinction between DVAs that are mere incidental findings and those that drain the AVM. In this small series, to our knowledge, all the cases included are AVM-DVA joint entities. CONCLUSIONS Although rare, AVMs and DVAs can coexist. The finding of a DVA in the proximity of a vascular lesion warrants consideration for catheter angiography as this does not necessarily 13 Zhang ACCEPTED MANUSCRIPT imply the lesion is a cavernous malformation. Patients with coexisting AVMs and DVAs tend to have hemorrhagic presentations, which are likely associated with the delicate hemodynamic balance between malformations. Contrary to traditional AVM management, it is important to preserve the draining vein via the DVA to ensure the safe, sustained RI PT circulatory outflow of the associated brain parenchyma, while achieving safe AVM obliteration. SC ACKNOWLEDGEMENTS preparation of this manuscript. TE D FUNDING M AN U We would like to acknowledge Cindy Samos and Christine Plant for their help in the This study was supported in part by funding from Bernard and Ronni Lacroute, and the AC C EP William Randolph Hearst Foundation to GKS. 14 Zhang ACCEPTED MANUSCRIPT REFERENCES 1. McCormick WF. The pathology of vascular (“arteriovenous”) malformations. J Neurosurg. 1966;24:807-816. doi:10.3171/jns.1966.24.4.0807. Mast H, Young WL, Koennecke HC, et al. Risk of spontaneous haemorrhage after RI PT 2. diagnosis of cerebral arteriovenous malformation. Lancet. 1997;350(9084):1065-1068. doi:10.1016/S0140-6736(97)05390-7. Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom R a, Zimmerman SC 3. RS. 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Endovascular treatment of brain AC C 32. EP doi:10.1227/01.NEU.0000255347.25959.D0. arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg. 2011;115(July):78-88. doi:10.3171/2011.2.JNS09830. 33. Kano H, Kondziolka D, Flickinger JC, et al. Stereotactic radiosurgery for arteriovenous malformations after embolization: a case-control study. J Neurosurg. 2012;117(2):265-275. doi:10.3171/2012.4.JNS111935. 34. Murray G, Brau RH. A 10-year experience of radiosurgical treatment for cerebral 18 Zhang ACCEPTED MANUSCRIPT arteriovenous malformations: a perspective from a series with large malformations. Clinical article. J Neurosurg. 2011;115(2):337-346. doi:10.3171/2011.3.JNS10814. 35. Alaraj A, Amin-Hanjani S, Shakur SF, et al. Quantitative assessment of changes in cerebral arteriovenous malformation hemodynamics after embolization. Stroke. 36. RI PT 2015;46(4):942-947. doi:10.1161/STROKEAHA.114.008569. Jo K., Kim J., Hong S., Lee J. Hemodynamic changes in arteriovenous malformations after radiosurgery: transcranial Doppler evaluation. World Neurosurg. 2012;77(2):316- Kashba SR, Patel NJ, Grace M, et al. Angiographic, hemodynamic, and histological M AN U changes in an animal model of brain arteriovenous malformations treated with Gamma EP TE D Knife radiosurgery. 2015;123(October):954-960. doi:10.3171/2014.10.JNS1435. AC C 37. SC 321. doi:10.1016/j.wneu.2011.06.061. 19 Zhang ACCEPTED MANUSCRIPT FIGURE LEGENDS Figure 1: Radiographic images of Patient 1 (A) MRI Axial T1 with contrast at presentation with a right parietal palm tree configuration characteristic of a DVA. (B) fMRI image with a RI PT right posterolateral orientation highlighting close proximity of the AVM (red arrow) and corticospinal tract (white arrow) of the foot. Also shown are the corticospinal tract of the hand in purple and the geniculocalcarine tract in yellow. (C and D) Angiography at pre- (C) SC and post- (D) embolization of the internal parietal branches arising from the right pericallosal M AN U artery with termination in the internal cerebral vein and superior sagittal sinus. Figure 2: Radiographic images of Patient 2 (A) MRI Coronal T1 with contrast at presentation showing a left parietal collection of veins with a central drainage, diagnostic for a DVA. (B and C) Angiography of the left internal carotid artery on anteroposterior view pre- TE D operatively (B) and post-resection (C) showing reduced vasculature of a left parietal AVM with anterior and posterior parietal feeding vessels and eventual drainage into the superior AC C EP sagittal sinus. 20 ACCEPTED MANUSCRIPT Table 1. Demographic information, treatment and outcomes for reported cases of AVM with coexisting DVA Case Author No. Year Age Sex Side Hemorrhage Clinical Presentation: Arterial Feeders Draining Veins AVM site Treatment Outcomes: Clinical and Radiograph 1 Huang16 1984 22 M - ICH - ACA, MCA Rolandic vein Temporal Resection NA 2 Lindquist22 1993 60 F - ICH + IVH - MCA Basal vein Temporal GKS Complete obliteration of AVM, no rebleed or radiation necrosis (31 mo F/U). 3 Lindquist22 1993 23 M - SAH - PICA Vermian vein Cerebellum GKS (both Partial obliteration but died from rebleed at (vermis) AVM and DVA 28 mo after irradiation. were irradiated) 4 Lindquist22 1993 20 M - SAH - - - Cerebellar hemisphere 5 Itoyama20 1994 50 M - ICH - PICA Inferior vermian Cerebellum Resection NA 6 Meyer23 1995 32 F - ICH + IVH Apoplectic episode of severe HA, LOC, severe R hemiparesis and complete sensory dysphasia MCA SSS Parietal Resection AVM, DVA was also "obliterated due to inadvertent injury Complete obliteration of both AVM and DVA. After 24 hrs, patient developed R arm plegia. At 6 mo F/U, limited R arm function, with minor difficulties in calculation and speech comprehension. 7 Akai17 1997 62 F L IVH Severe HA and vomiting ACA (frontal and pericallosal) SSS Frontal Embolization Complete obliteration. No new neurological deficits; No recurrence or rebleeding at 1 yr F/U. 8 Nussbaum24 1998 24 M - No HAs, vertigo, and blurred SCA vision VoG, Cerebellar Cerebellar vein Initial observation + embolization Initial conservative management, original AVM regressed. A new AVM formed at a different site after 10 yrs, treated with embolization and completely obliterated. 9 Kurita21 1999 39 M R No Incidental; investigation for transient dysarthria MCA TS Temporal SRS No hemorrhage, ischemia, or parenchymal radiation injury at 1 yr F/U. Angiography showed total obliteration of AVM with preservation of DVA 10 Yanaka27 2001 37 F R NA LOC with a 2 yr history of HA, nausea, and vomiting MCA Longitudinal caudate vein; ISS Parietal Proton-beam radiosurgery Complete obliteration of AVM, DVA unchanged. 11 Aksoy18 2000 11 M R No HA and temporal lobe seizure MCA VoG Temporal GKS Asymptomatic at 6 mo 12 Wurm26 2003 32 M L No HA and seizure - - Parietal Resection Seizure free at 6 mo 13 Fok6 2006 6 M R ICH Sudden occipital HA, vomiting, R dysmetria Known HHT 14 Fok6 2006 51 M L ICH HA, nausea, vomiting, R ACA, frontal RI PT VoG, lateral Cerebellum Embolization mesencephalic vein + precentral cerebellum vein TS Complete obliteration with improved clinical result at 161 mo of F/U SC M AN U SCA TE D EP AC C GKS x3 Frontal Improved dysmetria; F/U DSA at 4 mo confirmed a stable obliteration of the AVM and a patent DVA. Embolization x3 Partial obliteration of the AVM and a patent branches MANUSCRIPT + adjuvant GKS DVA ACCEPTED weakness, RLE hypoaesthesia, and history of hemorrhage 15 Fok6 2006 25 M R ICH L hemiparesis, L facial paresis, LOC ACA, precentral SSS gyrus branch of R pericallosal artery 16 Oran25 2008 18 F - ICH HAs - 17 Oran25 2008 24 F L ICH Hemiparesis 18 Oran25 2008 25 M R ICH 19 Erdem19 2012 late 30s F R 20 Erdem19 2012 7 F 21 Zhang 2017 29 22 Zhang 2017 34 Embolization N/A Frontal Embolization + GKS Symptom free at 6 yr with antiepileptics. New onset seizure at 1 yr, radiation induced necrosis. Complete obliteration of AVM. MCA VoG (lenticulostriate) Parietal GKS Symptom free at 5 yr (mRS 0) Clinical: Total resolution of hemiparesis within 2 yr Radiographic: decreased (but not complete) DVA shunting, obliteration of AVM Radionecrosis at 1 yr (MRI). Near total disappearance of shunting in DVA with patent collector vein at 1 yr (DSA) Hemiplegia ACA SSS Frontoparietal Embolization. of Improvement in neurologic status after AVM + operation. Occlusion of AVM. Near total Resection of disappearance of shunting in DVA with DVA/associated patent collector. Mild haemiparesis at 6 mo gyrus (2). Total disappearance of AVM and DVA at postoperative and F/U DSA at 6 mo No TNE: weakness numbness but with no neuro deficits; history of recurrent HAs, nausea, vomiting; ACA, MCA SSS Frontal Embolization x 3 Symptom free at 6 mo. 3 mo. F/U DSA confirmed stable obliteration of the AVM. R ICH LUE weakness and drooling after minor HI; history of frontal AVM diagnosed aged 3 ACA, MCA SSS Frontal Embolization x 2 Reduced size, some residual AVM, no new symptoms A post-embolization DSA showed residual AVM. F R ICH HA, L homonymous hemianopia MCA, PCA VoG Parietoocciptal Embolization + SRS Improvement in visual symptoms and Has. F L No TNE MCA, PCA SSS Parietal Partial resection Stable residual AVM on MRI. Seizure free + CKS at 11 mo F/U. SC - RI PT Frontal M AN U Table 1: Demographic and clinical outcomes for reported cases of AVM with coexisting DVA AC C EP TE D Abbreviations for Table 1: Anterior cerebral artery (ACA), arteriovenous malformation (AVM), developmental venous anomaly (DVA), follow up (F/U), gamma knife surgery (GKS), headaches (HAs), intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), left lower extremity (LLE), loss of consciousness (LOC), left upper extremity (LUE), middle cerebral artery (MCA), posterior cerebral artery (PCA), posterior inferior cerebellar artery (PICA), right lower extremity (RLE), right upper extremity (RUE), ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT subarachnoid hemorrhage (SAH), superior cerebellar artery (SCA), stereotactic radiosurgery (SRS), superior sagittal sinus (SSS), transient neurological episodes (TNE), hereditary hemorrhagic telangiectasia (HHT), follow up (F/U), head injury (HI), Vein of Galen (VoG), inferior sagittal sinus (ISS), transverse sinus (TS). AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT Highlights • AVM associated with a DVA is a rare and unique clinical entity • We report two cases and 20 previously published cases • The majority tend to have hemorrhage at presentation • Good clinical outcomes can be achieved via conservative and less invasive means • Treatment should involve preservation of the DVA