Conservative management of brain arteriovenous malformations: results of the prospective observation registry of a pragmatic trial
Authors: Darsaut Tim E. , Gentric Jean-Christophe , Heppner Jonathan , Lopez Camille , Jabre Roland , Iancu Daniela , Roy Daniel , Weill Alain , Bojanowski Michel W. , Chaalala Chiraz , Comby Pierre-Olivier , Roberge David , Cognard Christophe , Januel Anne-Christine , Sabatier Jean-Francois , Desal Hubert , Roualdes Vincent , Ferre Jean-Christophe , Alias Quentin , Papagiannaki Chrysanthi , Derrey Stéphane , Smajda Stanislas , Aldea Sorin , Gaberel Thomas , Barbier Charlotte , Barreau Xavier , Marnat Gaultier , Jecko Vincent , Anxionnat Rene , Merlot Isabelle , Nguyen Thanh N. , Abdalkader Mohamad , Dumot Chloe , Riva Roberto , Graillon Thomas , Troude Lucas , Kerleroux Basile , Ollivier Irene , Beaujeux Remy , Boulouis Grégoire , Planty-Bonjour Alexia , Spelle Laurent , Chalumeau Vanessa , Naggara Olivier , Lefevre Pierre-Henri , Le Corre Marine , Shotar Eimad , Carlson Andrew P. , Biondi Alessandra , Thines Laurent , Tawk Rabih G. , Huynh Thien , Fahed Robert , Findlay J. Max , Chabert Emmanuel , Zehr Justine , Gevry Guylaine , Klink Ruby , Viard Geraldine , Magro Elsa , Raymond Jean , _ _ , Iancu Daniela , Roy Daniel , Weill Alain , Raymond Jean , Comby Pierre-Olivier , Bojanowski Michel W. , Chaalala Chiraz , Jabre Roland , Roberge David , Darsaut Tim E. , Heppner Jonathan , O’Kelly Cian J. , Chow Michael M. C. , Findlay J. Max , Rempel Jeremy L. , Fahed Robert , Lesiuk Howard , Drake Brian , dos Santos Marlene , Gentric Jean-Christophe , Lopez Camille , Nonent Michel , Ognard Julien , El-Aouni Mourad Cheddad , Magro Elsa , Seizeur Romuald , Timsit Serge , Pradier Olivier , Desal Hubert , Boursier Romain , Thillays François , Roualdes Vincent , Piotin Michel , Blanc Raphael , Smajda Stanislas , Aldea Sorin , Cognard Christophe , Januel Anne-Christine , Sabatier Jean-François , Calviere Lionel , Gauvrit Jean-Yves , Eugene François , Ferre Jean-Christophe , Alias Quentin , Boucherit Julien , Morandi Xavier , Lecouillard Isabelle , Briens Aurelien , Ronziere Thomas , Vannier Stephane , Trystram Denis , Naggara Olivier , Rodriguez-Regent Christine , Kerleroux Basile , Barbier Charlotte , Gaberel Thomas , Emery Evelyne , Touze Emmanuel , Papagiannaki Chrysanthi , Derrey Stéphane , Eker Omer , Riva Roberto , Pellisou-Guyotat Isabelle , Guyotat Jacques , Berhouma Monsef , Dumot Chloé , Biondi Alessandra , Thines Laurent , Bougaci Nassim , Charbonnier Guillaume , Bracard Serge , Anxionnat René , Gory Benjamin , Merlot Isabelle , Civit Thierry , Bernier-Chastagner Valérie , Barreau Xavier , Marnat Gaultier , Jecko Vincent , Penchet Guillaume , Gimbert Edouard , Huchet Aymeri , Herbreteau Denis , Boulouis Grégoire , Bibi Richard , Ifergan Héloïse , Janot Kévin , Planty-Bonjour Alexia , Velut Stéphane , Brunel Hervé , Roche Pierre-Hugues , Graillon Thomas , Peyriere Hadrien , Kaya Jean-Marc , Touta Adamou , Troude Lucas , Boissonneau Sébastien , Clarençon Frédéric , Shotar Eimad , Sourour Nader , Lenck Stéphanie , Premat Kévin , Boch Anne-Laure , Cornu Philippe , Nouet Aurélien , Costalat Vincent , Bonafe Alain , Dargazanli Cyril , Gascou Gregory , Lefevre Pierre-Henri , Riquelme Carlos , Le Corre Marine , Beaujeux Rémy , Pop Raoul , Proust François , Cebula Hélène , Ollivier Irène , Spatola Giorgio , Spelle Laurent , Chalumeau Vanessa , Gallas Sophie , Ikka Léon , Mihalea Cristian , Ozanne Augustin , Caroff Jildaz , Chabert Emmanuel , Mounayer Charbel , Rouchaud Aymeric , Caire François , Ricolfi Frédéric , Thouant Pierre , Cao Catherine , Mourier Klaus-Luc , Farah Walid , Nguyen Thanh N. , Abdalkader Mohamad , Huynh Thien , Tawk Rabih G. , Carlson Andrew P. , Silva Luciana Alves Oliveira , de Lima Froio Nayara , Silva Gisele Sampaio , Mont’Alverne Francisco J. A. , Martins Jose Luri , Mendes George Nunes , Miranda Rodrigo Rivera 
Published: October 2024

OBJECTIVE
Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients.

METHODS
TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding.

RESULTS
From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1–2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7–1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2–1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4–13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1–7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4–7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9–3.6] per 100 patient-years; 2.0 [95% CI 1.3–2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6–2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1–8.9], p < 0.001), large (HR 2.6 [95% CI 1.1–6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2–5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1–4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7–4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0–4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0–3.2) per 100 patient-years.

CONCLUSIONS
Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.