Disclosures Surgical Treatment of AVMs Mizuho America, Inc.: - PowerPoint PPT Presentation

Disclosures Surgical Treatment of AVMs ● Mizuho America, Inc.: Royalties Michael T. Lawton, MD Michael T. Lawton, MD ● Stryker: Consultant Chief, Vascular Neurosurgery Chief, Vascular Neurosurgery Professor and Vice-Chairman Professor and Vice-Chairman Tong-Po Kan Endowed Chair Tong-Po Kan Endowed Chair University of California - San Francisco University of California - San Francisco Europe America Current Standards Current Standards ● Treat only ruptured AVMs ● Aggressive surgical resection ● Aggressive embolization ● Embolization as an adjunct ● Radiosurgery for residual AVM ● Radiosurgery for risky AVMs ● Shrinking role for surgery ● Stable role for surgery

AVM Management Onyx ● Divergent management philosophies ● Competitive, not complementary therapies ● How to decide? � Onyx embolization � Surgery ± embolization � Radiosurgery � Conservative observation AVM Embolization AVM Embolization Author Year Patients Morbidity Mortality Cure Rate Hemorrhage Perez-Higueras 2005 45 15.5% 2.0% 22% 8.9% ● Onyx and slowly staged reflux technique Song 2005 50 10.0% 0.0% 20% 6.0% ● Intranidal injection van Rooij 2007 44 4.6% 2.3% 16% 6.8% Weber 2007 93 5.4% 0.0% 20% n/a ● Cure rates with Onyx are better than with NBCA, still low Mounayer 2007 94 4.3% 3.2% 28% 8.5% ● Cure rates highest with low-grade AVMs Karsaridis 2008 101 8.0% 3.0% 28% 5.9% Pierot 2009 50 8.0% 2.0% 8% 8.0% ● Curative attempts associated with ↑complications Panagiotopoulos 2009 82 7.3% 2.4% 20% 12.2% ● Aggressive embolization can occlude draining veins Gao 2009 115 2.6% 0.9% 26% 2.6% Maimon 2010 43 2.3% 0.0% 37% 13.9% ● Adverse post-embo imaging findings common (40%) Xu 2011 86 3.5% 1.2% 19% 7.0% Saatci 2011 350 4.3% 1.4% 51% 4.0% Abud 2011 17 5.9% 0.0% 94% 11.7% Pierot 2013 127 5.1% 4.3% 24% 8.5% TOTAL 1297 6.2% 1.6% 29% 8.0%

AVM Radiosurgery Radiosurgery for Low-Grade AVMs ● Minimally invasive appeal Author Year Patients Morbidity Mortality Cure Rate Hemorrhage ● Improved targeting and dosing Pollock 1994 65 5.0% 3.0% 86.0% 7.7% Yamamoto 1996 19 n/a 0.0% 63.2% 2.5% ● Low radiation-induced complications, M/M Meder 1997 57 n/a n/a 65.0% n/a ● But, intermediate cure rates Friedman 2003 107 n/a n/a 66.4% 10.4% Nataf 2007 27 n/a 0.0% 77.8% 10.0% ● Latency hemorrhage (2 - 3 years) Kano 2012 217 3.2% 2.8% 93.0% 6.0% ● Embolization decreases radiosurgical obliteration Fokas 2013 24 n/a n/a 61.0% 6.0% Koltz 2013 33 12.1% 0.0% 88.0% 9.1% Sheehan 2014 502 5.6% n/a 76.1% 5.6% Total 1051 6.5% 1.2% 75.2% 7.2% ARUBA Trial ARUBA Primary Outcomes Critique 1: 13% Randomization Best AVMs excluded (↑rupture risk, ↓tx risk) Worst AVMs included ↓rupture risk, ↑tx risk Low external validity As randomized As treated (not generalizable)

Critique 2: Treatment Bias Critique 3: Incomplete Obliteration As treated Interventional Therapy Endovascular embolization 30 32% 81% Radiosurgery 31 33% Combined embolization-radiosurgery 15 16% Neurosurgery (± embolization) 17 18% ● Surgery is the gold-standard ● No data on cure rate ● Non-surgical trial with infrequent, delayed cures & ongoing rupture risks Medical Outcome = Natural history Interventional Outcome = Procedural morbidity + Latency hemorrhage AVM Surgery Low-Grade AVMs ● AVM resection is the “gold standard” UCSF Microsurgical Experience ● Patient selection to ensure low surgical risk ● Review period (years) 16 (supplemented Spetzler-Martin grades) ● Total AVMs 640 ● Conservative embolization with lower risks ● Grade I/II AVMs 232 ● Meticulous surgical approaches and technique � Grade I 76 ● High cure rates � Grade II 156 ● Immediacy (no latency period) ● Mean age (years) 38 ● Hemorrhagic presentation 50%

Low-Grade AVM Surgery UCSF ARUBA Patients Unruptured Ruptured p-Value Total ● Screened 473 Total 112 120 232 Angiographic Outcome 0.46 ● Eligible 87 Complete 104 98% 109 97% 213 98% Residual 2 2% 3 3% 5 2% ● Enrolled 4 Functional Outcome 0.0008 ● Excluded (<30d followup) 10 0-1 91 91% 70 65% 161 78% 2 6 6% 25 23% 31 15% ● Analyzed 74 3 3 3% 5 5% 8 4% 4 0 0% 2 2% 2 1% 5 0 0% 4 4% 4 2% 6 0 0% 1 1% 1 0% Improved/Unchanged 96 96% 105 98% <0.0001 201 97% Worse 4 4% 2 2% 6 3% Mean Follow-up (years) 1.8 1.6 1.7 UCSF ARUBA Patients Low-Grade AVM Surgery Author Year Patients Morbidity Mortality Cure Rate Hemorrhage ● Treatment 61 Spetzler, Martin 1986 44 2.3% 0% n/a n/a � Surgery 20 Sundt 1989 84 2.2% 0% 100% 0% � Embolization/Surgery 23 Heros 1990 47 2.2% 2.2% 100% 0% Sisti, Stein 1993 67 1.5% 0% 94% 0% � Radiosurgery 15 Hamilton, Spetzler 1994 40 0.0% 0% 100% n/a Schaller, Schramm 1997 50 3.2% 0% 98% 2% Schaller, Schramm 1998 81 0.0% 0% n/a n/a ● Primary Outcome 10 Harbaugh 1998 26 3.8% 0% 100% 0% � Observation 1 (8%) Hartmann 2000 48 6.6% 0% n/a n/a Morgan 2004 220 0.9% 0.5% 100% 0% � Surgery 5 (11%) Davidson, Morgan 2010 296 0.7% 0% 97% n/a � Radiosurgery 4 (27%) Lawton 2014 232 2.4% 0.5% 98% 0% Total 1235 2.2% 0.3% 98.5% 0.3%

Critique 5: Study Duration Summary: Low-Grade AVMs ● 33 months mean follow-up Therapy Patients Morbidity Mortality Cure Rate Hemorrhage ● Surgical patients cured, no further risk (plateau) Embolization 1297 6.2% 1.6% 29.0% 8.0% ● Medical patients remain at risk (slope) Radiosurgery 1051 6.5% 1.2% 75.2% 7.2% Surgery 1235 2.2% 0.3% 98.5% 0.3% All AVMs* Patients Complications Case Fatality Obliteration Hemorrhage F/U (pers yrs) Embolization 1019 6.60% 0.96 13% 1.7 137 Radiosurgery 9436 5.10% 0.5 38% 1.7 202 Surgery 2549 7.40% 1.1 96% 0.18 72 10 years * Systematic meta-analysis of 13,698 patients (van Beijnum et al, JAMA 2011) BARBADOS Trial UCSF Experience ● Beyond ARUBA: ● Randomized ● Best neurosurgeons ● AVMs unruptured ● Consecutive series, single surgeon ● Don’t embolize ● Review period (years) 16 ● Only low-grades ● Total Brain AVMs 642 ● Surgical cure ● Patients 640 Beginning soon!

AVM Resection Military Battle Surgical Resection ● Frontal ● War Resection ● Temporal ● Soldier Neurosurgeon ● Parieto-Occipital ● Battlefield Anatomy ● Ventricular ● Battle plan Surgical steps ● Deep ● Enemy AVM subtypes ● Brainstem ● Cerebellar AVM Subtypes (32) Frontal AVMs ● Lateral Frontal ● Lateral Temporal ● Lateral Parieto-Occipital ● Medial Frontal ● Basal Temporal ● Medial Parieto-Occipital ● Paramedian Frontal ● Sylvian Temporal ● Paramedian Parieto-Occipital ● Basal Frontal ● Medial Temporal ● Basal Parieto-Occipital ● Sylvian Frontal Medial Paramedian Lateral ● Callosal ● Pure Sylvian ● Suboccipital Cerebellar ● Anterior Midbrain ● Ventricular Body ● Insular ● Vermian Cerebellar ● Posterior Midbrain ● Atrial ● Basal Ganglia ● Tonsillar Cerebellar ● Anterior Pontine ● Temporal Horn ● Thalamus ● Tentorial Cerebellar ● Lateral Pontine ● Petrosal Cerebellar ● Anterior Medullary ● Lateral Medullary Basal Sylvian

Temporal AVMs Parieto-Occipital AVMs Lateral Medial Lateral Medial Paramedian Basal Sylvian Basal Ventricular AVMs Deep AVMs Callosal Ventricular Body Sylvian Insular Basal Ganglial Temporal Horn Atrial Basal Ganglial Thalamic Thalamic

Brainstem AVMs Cerebellar AVMs Anterior Midbrain Anterior Pontine Anterior Medullary Suboccipital Vermian Posterior Midbrain Lateral Pontine Lateral Medullary Petrosal Tentorial Tonsillar Steps for AVM Resection 1. Exposure 1. Exposure 2. Subarachnoid dissection 3. Draining vein 4. Feeding arteries 5. Pial dissection 6. Parenchymal dissection 7. Ependymal dissection 8. AVM Resection

2. Subarachnoid Dissection 3. Draining Vein Absolute preservation Compass Odometer 4. Feeding Arteries 5. Pial Dissection Fronts

6. Parenchymal Dissection 6. Parenchymal Dissection Compact Diffuse 7. Ependymal Dissection 8. Resection

The Battle Plans Lateral Frontal AVM Lateral Frontal AVM AVM Surgery ● Each AVM is not unique ● Recognize types and subtypes ● Choose your battles and patients wisely ● Study angiographic, radiographic anatomy ● Know the basic 8 steps strategy for resection ● Execute the specific battle plan for each AVM ● Be courageous ● Strive for excellence (ARUBA)

Surgical Courage ARUBA Aftermath ● More than technical steps ● Ruptured AVMs should be managed surgically ● One mistake away from disaster ● High risk ● Unruptured AVMs: ● Must handle the danger and intensity � Low-grade AVMs → BARBADOS � Silent microhemorrhage � High-risk AVMs (morphology, genetics, etc.) “It’s not what we have in our hands, but how we use it” � Downgraded high-grade AVMs after VS-SRS Silent Microhemorrhage Evidence of Old Hemorrhage ● The AVM’s “sentinel hemorrhage” � Aneurysm: symptoms with blood � AVM: sz or no symptoms with blood ● “Unruptured” AVMs have silent intralesional hemorrhage ● SIM seen histopathologically (hemosiderin, macrophages) ● SIM seen radiographically (EOOH, evidence of old hemorrhage)