A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

BACKGROUND: The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. OBJECTIVE: To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. METHODS: Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. RESULTS: Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). CONCLUSION: Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Economic analysis of n-butyl cyanoacrylate compared with ethylene vinyl alcohol copolymer liquid embolic embolization of brain arteriovenous malformations (bAVMs) from a US hospital perspective.

BACKGROUND: In US hospitals, the liquid embolic systems (LESs) n-butyl cyanoacrylate (n-BCA) and ethylene vinyl alcohol copolymer (EVOH) are used for brain arteriovenous malformation (bAVM) embolization to achieve presurgical devascularization. The aim of this study was to perform an economic analysis comparing four techniques for bAVM embolization based on LES, ancillary device, and angiography suite time costs. METHODS: An economic model was developed comparing the embolization costs for n-BCA, EVOH with the plug and push technique, EVOH with detachable-tip microcatheters, and EVOH with balloon microcatheters. Per procedure costs were calculated for bAVMs with one to four pedicles. Annual cohort analyses were performed to evaluate the potential impact for low and high-volume centers. Sensitivity analyses were performed to determine cost drivers. RESULTS: The analyses showed that the n-BCA technique was the least costly of the four techniques. Total per procedure costs for one to four embolized pedicles ranged from $5941 to $10,074 for the n-BCA technique, $8428 to $30,345 for the EVOH balloon microcatheter technique, $12,711 to $47,477 for the EVOH plug and push technique, and $13,900 to $52,233 for the EVOH detachable-tip microcatheter technique. Cohort analyses costs for 52 annual cases ranged from $308,953 to $523,838 with the n-BCA technique and from $722,816 to $2,716,096 with the EVOH detachable-tip microcatheter technique. CONCLUSIONS: Procedure costs associated with n-BCA are lower than those with each of the three EVOH techniques examined. Future cost analyses should compare the costs of new LES products once available.

Comparative cost analysis of liquid embolization systems for brain arteriovenous malformation using a real-world US hospital database: TRUFILL® versus OnyxTM.

BACKGROUND: Liquid embolic systems (LES) such as n-butyl cyanoacrylate-based TRUFILL® and ethylene vinyl-alcohol copolymer-based OnyxTM are widely used for the embolization of brain arteriovenous malformations (bAVMs). The purpose of this study was to compare hospital cost and length of stay (LOS) among unruptured bAVM patients undergoing embolization procedures with TRUFILL versus Onyx LES. METHODS: Adult patients with unruptured bAVMs undergoing endovascular embolization with TRUFILL or Onyx LES between January 1, 2010 and June 30, 2020 were identified from the Premier Healthcare Database. Baseline covariates among the two groups were balanced using propensity score matching. Outcomes including total procedure cost, supply cost, and LOS were examined. A Generalized Estimating Equation model was used to assess outcomes in the matched cohorts. RESULTS: A total of 1072 patients were included in the study; 140 embolized with TRUFILL (mean age 47.06 [15.72] years, 45.70% male) and 932 embolized with Onyx (mean age 46.80 [16.65] years, 52.30% male). In the post-match cohort, the total procedure costs were lower for the TRUFILL (n = 130) versus Onyx (n = 333) group, though not significantly ($36,798 vs. $40,988; odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.73-1.10; p = 0.30). However, supply cost was significantly lower for hospitalizations with TRUFILL compared to Onyx use ($13,281 vs. $16,371, OR = 0.81, 95% CI: 0.68, 0.98; p = 0.026). Hospital LOS was similar in these two groups (TRUFILL: 4.05 vs. Onyx: 4.06 days; OR = 1.00, 95% CI: 0.70, 1.42; p = 0.99). CONCLUSIONS: In a large, multi-center, real-world sample of patients undergoing bAVM embolization, TRUFILL use was associated with significantly lower supply cost compared to Onyx use.

Assessment of gamma knife radiosurgery for unruptured cerebral arterioveneus malformations based on multi-parameter radiomics of MRI.

OBJECTIVE: The treatment of Gamma knife radiosurgery (GKS) for unruptured Arteriovenous Malformations (AVM) remains controversial. A safe, effective and non-invasive method to predict outcome seems attractive for GKS. The purpose of this study was to develop and validate a MRI based multi-parameter radiomics model predicting the outcome of GKS for unruptured AVM. METHODS: Eighty-eight unruptured AVM patients who initial underwent GKS between January 2011 and December 2016 in our hospital were included in this retrospective study. Patients were divided into two groups named as favourable and unfavourable outcome, according to the clinical outcome. Favourable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). Multivariate logistic regression analysis was used to select appropriate clinical features and construct a clinical predicting model. In terms of radiomic model, manually segmentation and radiomics extracted were performed on each AVM lesions. Finally, 1684 radiomics features were extracted and Recursive Feature Elimination (RFE) method combined with Random forest classifier were used for feature selection and model construction. The performance of the radiomics model was evaluated by the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, the favourable group was further divided into early and late respond subgroup according to the time of obliteration evaluated by 2 years. The selected features were further compared according the respond time. RESULTS: The median duration of neuroimaging follow-up was 65 months, 56 patients showed favourable outcome and 17 patients were observed obliteration within 2 years. The radiomics model constructed by 12 selected features achieved significant higher AUC of 0.88 (95% confidence interval 0.87-0.90) than traditional scoring system for predicting AVM outcome. Two selected radiomics features named "Dependence Variance" and "firstorder-Skewness" were found significant difference between the patients with early or late-respond. CONCLUSIONS: The results suggest that the radiomics features could be successfully used for the pretreatment prediction of outcome for GKS in unruptured AVMs, which is helpful for decision-making process on unruptured AVM patients.

Eficacia y seguridad de la embolización endovascular de malformaciones arteriovenosas cerebrales y fístulas arteriovenosas durales (intracraneales y espinales) con líquido hidrofóbico precipitante inyectable / Efficacy and safety of endovascular embolization of cerebral arteriovenous malformations and dural arteriovenous fistulas (intracranial and spinal) with injectable precipitating hydrophobic liquid

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente documento de evaluación de tecnología sanitaria (ETS), el cual expone la evaluación de la eficacia y seguridad del procedimiento de embolización endovascular de malformaciones arteriovenosas cerebrales (MAC) y fístulas arterio-venosas durales (FAVD), con el uso del agente liquido hidrofóbico precipitante inyectable, en comparación con sustancia liquida embolizante convencional disponible en EsSalud (Código SAP: 20103358). Mediante la Carta N° 307-SERV.NRX.DPTO.NC-HNGAI-ESSALUD-2017, los médicos especialistas del Servicio de Neurorradiología del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI), a través de la gerencia de la Red Prestacional Almenara, solicitan al Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) la evaluación de la tecnología "sistema pre cargado de líquido inyectable precipitante", para evaluar su posible inclusión al listado de material médico disponible en EsSalud para su utilización en procedimientos de embolización de MAC y FAVD. ASPECTOS GENERALES: Las malformaciones arteriovenosas cerebrales (MAC) son malformaciones caracterizadas por una conexión directa de una arteria a una vena, sin una red capilar en el medio. La prevalencia de MAC detectadas, asintomáticas o sintomáticas, en la población es de 10 a 18 por 100,000 adultos (Al-Shahi et al. 2002). La incidencia es de -z1.3 por 100,000 personaaños (Gabriel et al. 2010; Stapf et al. 2003). En los estudios poblacionales, las MAC sintomáticas se manifiestan como accidentes cerebro vasculares (ACV) hemorrágico (58 %), convulsiones (34 %), u otros síntomas como el déficit neurológico progresivo (8 %) (da Costa et al. 2009; Stapf et al. 2006). Este último fenómeno se atribuye a la isquemia local derivado del "robo arterial" (esto es, la sangre llega a la zona, pero por no tener capilares apropiados, esa zona no se irriga adecuadamente) u obstrucción del flujo venoso (hipertensión venosa) (Mast et al. 1995). Esta fisiopatología genera también convulsiones (Fierstra et al. 2010). METODOLOGÍA: Se realizó una búsqueda sistemática de información con el objetivo de identificar la mejor evidencia disponible a la fecha (octubre 2021) sobre la eficacia y seguridad de la embolización de MAC y FAVD con PHIL®, en comparación con Onyx O. Se realizó una búsqueda bibliográfica avanzada en las bases de datos de PubMed, Cochrane Library y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). La búsqueda sistemática fue suplementada con una búsqueda manual en la lista de referencias bibliográficas de los estudios incluidos en la ETS. Además, se realizó una búsqueda de literatura gris en el motor de búsqueda Google, a fin de poder identificar otras publicaciones de relevancia que pudiesen haber sido omitidas por la estrategia de búsqueda o que no hayan sido publicadas en las bases de datos consideradas. Asimismo, se realizó una búsqueda dentro de las páginas web pertenecientes a grupos que realizan ETS y GPC, incluyendo, el National institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualitát und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo de la embolización de MAC, como la American Heart Association, la American Stroke Association, y la European Stroke Organization. Por último, se realizó una búsqueda de estudios clínicos en ejecución o aún no terminados en ClinicalTrials.gov. RESULTADOS: La declaración científica de la AHA/ASA (American Heart Association/American Stroke Association) acerca del manejo de las MAC (Derdeyn et al. 2017), fue preparado por miembros de la AHA y demás expertos invitados, quienes después de la revisión de la literatura hicieron recomendaciones. En esta declaración se señala que existen tres herramientas terapéuticas complementarias para el cierre definitivo del nido de la MAC. El primero es la resección microquirúrgica (MC), el cual debe realizarse primariamente o después de la embolización para reducir el riesgo de sangrado durante la cirugía y facilitar la remoción completa y sin complicaciones. El segundo, es la radiocirugía estereotáctica (RC), la cual también debe realizarse primariamente o después de la embolización para reducir el volumen del nido y potencialmente mejorar las tasas de obliteración de los nidos. El tercer método es la embolización endovascular per se. Aunque ésta es frecuentemente usada como un predecesor de la MC o la RC, hay casos en los que puede ser la terapia definitiva. La información a la que se hace referencia proviene de series de casos, mono o multicéntricos, en su mayoría conteniendo un número pequeño a moderado de pacientes; además, en este documento de recomendaciones no hay una gradación de las estrategias de manejo según calidad de evidencia. Respecto a la embolización endovascular, los estudios referidos correspondían al uso de los siguientes agentes inyectables: Onyx® y nbutil cianoacrilato (n-BCA). No se incluyó en este documento ningún estudio sobre el agente PHILO. CONCLUSIÓN: Por lo expuesto, el IETSI no aprueba el uso del agente liquido embolizante PHIL® en el tratamiento de las malformaciones arteriovenosas cerebrales y fístulas arteriovenosas durales (intracraneales y espinales).

Significant venous flow alterations following brain arteriovenous malformation Surgery: Assessment by transcranial colour duplex.

Brain arteriovenous malformation (bAVM) resection imposes several post-operative clinical challenges including intracranial haemorrhage (ICH). Daily non-invasive monitoring of haemodynamic measurements may be useful in predicting post-operative ICH. This prospective study used transcranial colour duplex (TCCD) and central aortic pressure (CAP) measurements to evaluate 15 bAVM patients pre-operatively and daily ≤ 14 days post-operatively. TCCD measurements of middle cerebral artery and veins included peak systolic (PSV), end diastolic (EDV), and pulsatility indices (PI). Parameters were compared with 7 craniotomy patients (non-bAVM craniotomy/surgical group). Normal reference values included 20 healthy volunteers. Significant middle cerebral vein MCV changes in bAVM patients occurred; Maximal PSV was significantly higher (median 47 cm/s) compared to non-bAVM craniotomy/surgical controls (median 17 cm/s, p = 0.0123); maximal PI was significantly higher (median 0.99, p = 0.005) compared to the non-bAVM craniotomy/surgical controls (median 0.49). In 8 of 15 patients, increased MCV velocity and pulsatility "stabilised" within 14 days post-operatively. Mean number of days for the 8 patients to reach stable state was 5.9 days, (range 0-9 days). To our knowledge, this is the first imaging study demonstrating significant venous changes post bAVM resection. Significant increased venous flow occurs in pial veins bilaterally. Increased pressure of venous flow is evidenced by a significant increase in diameter and pulsatility. Subsequently, haemorrhagic complications may be due distal constriction of the pial veins causing venous hypertension. The cause of the dilated vascular bed is unknown.

Multimodality Management in bAVM Surgery - Recent Experience from International Cerebrovascular Fellowship.

BACKGROUND: Arteriovenous malformation (bAVM) presents maldevelopment of the brain's vessels with a direct connection between cerebral arteries and veins. By current data, patients from Spetzler Ponce A (SP) are found to benefit from the treatment. Considering the outcome, most of SP C and some of the SP B are the most debatable. OBJECTIVE: Arteriovenous malformation presents maldevelopment of the brain's vessels with a consequent direct connection between cerebral arteries and veins. The annual risk of hemorrhage in adults is reported for 2-3 %. They usually present with unilateral headaches seizures and intracranial hemorrhage. By current data, patients from Spetzler Ponce A (SP) are found to benefit from the treatment. Considering the outcome, most of SP C and some of the SP B are the most debatable. METHODS: The study included a cohort of bAVM patients referred to Fujita Health University Bantane Hotokukai Hospital, Nagoya, Aichi, Japan where the main author (AA) has completed an international cerebrovascular fellowship under the mentorship of Professor Yoko Kato. Japanese Stroke Guidelines (JSG) were used for the treatment decision. Patients were graded according to the Spetzler Ponce (SP) system. Considering American Heart Association criteria (AHA), embolization was used as a part of multimodal treatment. Intraoperative microscopic video tools included Indocyanine green ICG, FLOW 800 and dual image video angiography DIVA. Clinical outcomes were measured using Modified Ranking Score (mRs). RESULTS: A total of eleven patients with brain bAVM were studied with a median age of 32 years [IQR = 22-52]. There were ten patients presented with supratentorial and a single patient with infratentorial AVM. Patients were graded according to the Spetzler Ponce (SP) system. There were eight patients in SP A (72,7%), one in group B (9 %) while the rest of them were in C (18 %). Two patients had associated aneurysms that required treatment. The median size of the AVM nidus was 3,50 cm [IQR= 2-5]. Deep venous drainage was found in six patients while three were located in eloquent zones. Clinical outcomes were considered good by mRs <2 in eight patients, seven from the surgically treated group (72,7 % respectively). Surgery median length time was 427, 5 minutes; [IQR =320 - 463] with complete AVM resection in all patients and no mortality recorded in this cohort with the median follow up of 39,5 months [IQR = 19-59]. CONCLUSION: Ideal management of bAVM is still controversial. Those complex vascular lesions require multimodal treatment in a majority of cases in highly specialized centers. In SP A patients, surgery provides the best results with a positive outcome and a small number of complications. With the improvement of endovascular feeder occlusion SP B patients become prone to a more positive outcome. Nowadays, intraoperative microscopic tools such as FLOW 800, ICG and DIVA are irreplaceable while improving safety to deal with bAVM. For SP C patients, a combination of endovascular and stereotactic radiosurgery was found to be a good option in the present time.

Eficacia y seguridad de la embolización de malformaciones arteriovenosas cerebrales con microcatéter compatible con sustancia embolizante de punta desprendible / Efficacy and safety of embolization of cerebral arteriovenous malformations with microcatheter compatible with detachable tip embolizing substance

INTRODUCCIÓN: El presente documento de evaluación de tecnología sanitaria (ETS) expone la evaluación de la eficacia y seguridad del procedimiento de embolización de malformaciones arteriovenosas cerebrales (MAC) con el uso del microcatéter compatible con sustancia embolizante de punta desprendible (MPD), en comparación con el microcatéter compatible con sustancia embolizante convencional (MC). Una malformación arteriovenosa cerebral (MAC) es un entramado patológico de vasos sanguíneos1 de la vasculatura cerebral, que causa la desviación de la sangre de las arterias a las venas; pasando por alto el tejido cerebral. Esta alteración ocasiona que los tejidos circundantes a la MAC no reciban oxígeno suficiente. Las arterias y venas de la MAC pueden debilitarse y romperse; causando hemorragia intracerebral o daño cerebral transitorio o permanente.  En el Perú, la información epidemiológica sobre las MAC es escasa. En la ciudad de Ayacucho se ha reportado que el 4.3 % de los casos diagnosticados con vasculopatías encefálicas, en adultos de 20 a 60 años de edad, corresponden a MAC. Además, según la información proporcionada por los especialistas en Neurorradiología del Hospital Nacional Guillermo Almenara Irigoyen (HNGAI) de EsSalud, estos suelen recibir hasta 60 casos anuales de MAC.  Uno de los enfoques de tratamiento para el manejo de las MAC, es la embolización; empleando sustancias con dimetilsulfóxido (DMSO). Estas sustancias son inyectadas en la MAC a través de un microcatéter compatible con la sustancia embolizante. La finalidad es crear un coágulo artificial dentro de la malformación; aislándola de la circulación y reduciendo o eliminando la sintomatología asociada. En la actualidad, en EsSalud, este procedimiento se realiza mediante la tecnología "microcatéter compatible con sustancia embolizante convencional" (MC). Sin embargo, los especialistas del HNGAI mencionan que, en ocasiones, la punta de este catéter puede quedar atrapada en la sustancia embolizante. Luego, al intentar retirar el catéter, existe el riesgo de hemorragia y/o ruptura del dispositivo. Por este motivo, los especialistas del HNGAI solicitan al Instituto de Evaluación de Tecnologías Sanitarias en Salud e Investigación (IETSI) la evaluación de la eficacia y seguridad del uso del "microcatéter compatible con sustancia embolizante de punta desprendible" (MPD); la cual podría reducir el riesgo de hemorragia y/o ruptura del microcatéter asociados al atrapamiento de su punta durante los procedimientos de embolización. MÉTODOS: Se realizó una búsqueda sistemática de información con el objetivo de identificar la mejor evidencia disponible a la fecha (marzo 2021) sobre la eficacia y seguridad de la embolización de MAC con el MPD, en comparación con MC. Se realizó una búsqueda bibliográfica avanzada en las bases de datos de PubMed, Cochrane Library y LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud). La búsqueda sistemática fue suplementada con una búsqueda manual en la lista de referencias bibliográficas de los estudios incluidos en la ETS. Además, se realizó una búsqueda de literatura gris en el motor de búsqueda Google, a fin de poder identificar otras publicaciones de relevancia que pudiesen haber sido omitidas por la estrategia de búsqueda o que no hayan sido publicadas en las bases de datos consideradas. Asimismo, se realizó una búsqueda dentro de las páginas web pertenecientes a grupos que realizan ETS y GPC; incluyendo, el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institut für Qualitát und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), además de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo de la embolización de MAC, como la American Heart Association, la American Stroke Association, y la European Stroke Organization. RESULTADOS: Se identificaron 418 estudios a partir de la búsqueda bibliográfica; de los cuales 412 fueron elegibles para tamizaje por título y resumen, luego de eliminar duplicados. La selección de estudios por título y resumen se realizó mediante una evaluación por pares empleando el aplicativo web Rayyan. Como resultado, se obtuvieron 12 estudios elegibles para evaluación a texto completo por un evaluador (ocho como resultado de la búsqueda sistemática y cuatro de la búsqueda manual); de los cuales cuatro estudios fueron incluidos en la presente evaluación. CONCLUSIONES: El presente dictamen preliminar expone una síntesis de la mejor evidencia disponible a la fecha (21 de marzo del 2021) sobre la eficacia y seguridad de la tecnología MPD en comparación con MC para el tratamiento de embolización de MAC empleando una sustancia embolizante con DMSO. Actualmente los pacientes que acuden a EsSalud con diagnóstico de MAC son sometidos al procedimiento de embolización con sustancias embolizantes (incluidas las sustancias con DMSO) utilizando el MC, que es la tecnología actualmente disponible en la institución para llevar a cabo estos procedimientos. Se ha incluido para evaluación una GPC basada en consenso de expertos (Kato et al. 2019), un ensayo clínico de fase IV (Meyers et al. 2021), y dos estudios observacionales sin grupo de comparación (Akmangit et al. 2014, Ozpar et al. 2019). La GPC no menciona en sus recomendaciones (u otras secciones del documento) a la tecnología MPD para el tratamiento de embolización de las MAC (Kato et al. 2019). Sin embargo, si mencionó dentro de sus recomendaciones que la sustancia con DMSO es la de elección para llevar a cabo este procedimiento. La evidencia de sustento de esta mención empleó en su mayoría MC o no precisó qué microcatéter se utilizó para llevar a cabo los procedimientos de embolización. Se han identificado similitudes en cuanto al reporte de tasas de EA, EAS, y muertes posiblemente relacionadas al uso de las tecnologías MPD y MC. No obstante, las tasas del desenlace de retención de la punta del catéter en la sustancia embolizante son notablemente mayores con el uso de la tecnología MPD, en comparación con las tasas de entrampamiento con retención de una fracción del MC. Existe riesgo de migración de la punta desprendible del MPD, cuando esta queda retenida en la sustancia embolizante; lo cual podría tener consecuencias serias para los pacientes poniendo en riesgo sus vidas. Por ello, se tendría que realizar un monitoreo periódico exhaustivo de estos pacientes para reducir el riesgo probable de complicaciones. Además, se debe tener en cuenta los reportes frecuentes de desprendimiento prematuro y embolización de la punta del MPD, que podrían ocasionar EAS y complicaciones en los pacientes con MAC durante los procedimientos de embolización. Dado que actualmente en la institución se cuenta con la experiencia de uso de la tecnología MC, y que, con la evidencia disponible, no es posible demostrar un beneficio clínico adicional en términos de eficacia y seguridad de la tecnología MPD con respecto al MC. Por lo expuesto, el IETSI no aprueba el uso de microcatéter compatible con sustancia embolizante de punta desprendible.

Living with a Brain AVM: A Quality of Life Assessment.

BACKGROUND AND PURPOSE: Brain arteriovenous malformations (AVM) are uncommon vascular lesions with the risk of hemorrhage, epileptic seizures, neurological deficits, and headache. Comparing the risks of the natural history and that of preventive treatment, a recent study has found observation more beneficial than treatment for unruptured AVMs. This study, however, did not consider the long-term impact of carrying a brain AVM on everyday activities. In this study we analyzed the Quality Of Life (QOL) of patients with untreated AVMs, a measure increasingly used in clinical trials to asses this kind of impact. METHODS: We enrolled 36 patients with unruptured, untreated brain AVM from our hospital database and measured their QOL retrospectively using the EQ-5D-5L questionnaire. As a control group we used the results of the Research Report, a nationwide study based on the quality of life of 5534 healthy Hungarians in 2002. Due to the low number of cases, statistical analysis could not be made. RESULTS: Headache proved to be the most common AVM-related sign in our cohort (40%, n = 17), with a female predominance; neurological deficit was detected in 33% (n = 14), while epileptic seizures occurred in 26% (n = 11), more commonly affecting male subjects. Anxiety and discomfort seemed to be the most prevalent influencing factors on QOL, especially in the youngest age group (18-34 years). Female subjects showed a greater dependence than men in all age groups, though males had a more significant impairment in their usual activities. Older patients were affected more significantly in their self-care and usual activities compared with the younger population. CONCLUSIONS: Untreated AVMs have a significant negative impact on patients carrying unruptured brain AVMs, as proved by QOL assessment. Beside neurological deficits, this impact should also be considered in the therapeutic decision.

Does Endovascular Treatment with Curative Intention Have Benefits for Treating High-Grade Arteriovenous Malformation versus Radiosurgery? Efficacy, Safety, and Cost-Effectiveness Analysis.

BACKGROUND: The treatment of high-grade arteriovenous malformations (AVMs) remains challenging. Microsurgery provides a rapid and complete occlusion compared with other options but is associated with undesirable morbidity and mortality. The aim of this study was to compare the occlusion rates, incidence of unfavorable outcomes, and cost-effectiveness of embolization and stereotactic radiosurgery (SRS) as a curative treatment for high-grade AVMs. METHODS: A retrospective series of 57 consecutive patients with high-grade AVM treated with embolization or SRS, with the aim of achieving complete occlusion, was analyzed. Demographic, clinical, and angioarchitectonic variables were collected. Both treatments were compared for the occlusion rate and procedure-related complications. In addition, a cost-effectiveness analysis was performed. RESULTS: Thirty patients (52.6%) were men and 27 (47.4%) were women (mean age, 39 years). AVMs were unruptured in 43 patients (75.4%), and ruptured in 14 patients (24.6%). The presence of deep venous drainage, nidus volume, perforated arterial supply, and eloquent localization was more frequent in the SRS group. Complications such as hemorrhage or worsening of previous seizures were more frequent in the embolization group. No significant differences were observed in the occlusion rates or in the time necessary to achieve occlusion between the groups. The incremental cost-effectiveness ratio for endovascular treatment versus SRS was $53.279. CONCLUSIONS: Both techniques achieved similar occlusion rates, but SRS carried a lower risk of complications. Staged embolization may be associated with a greater risk of hemorrhage, whereas SRS was shown to have a better cost-effectiveness ratio. These results support SRS as a better treatment option for high-grade AVMs.

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture.

BACKGROUND: Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. METHODS: Multimodal neurologic monitoring data from the initial 3 days after cerebral AVM rupture were retrospectively analyzed in children (< 18 years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12 months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. RESULTS: Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). CONCLUSIONS: After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support.

Dosimetric comparison of iPlanⓇ Pencil Beam (PB) and Monte Carlo (MC) algorithms in stereotactic radiosurgery/radiotherapy (SRS/SRT) plans of intracranial arteriovenous malformations.

Stereotactic radiosurgery/radiotherapy (SRS/SRT) is a hypofractionated treatment where accurate dose calculation is of prime importance. The accuracy of the dose calculation depends on the treatment planning algorithm. This study is a retrospective dosimetric comparison of iPlanⓇ Monte Carlo (MC) and Pencil Beam (PB) algorithms in SRS/SRT plans of cranial arteriovenous malformations (AVMs). PB plans of 60 AVM patients who were already treated using 6 MV photons from a linear accelerator were selected and divided into 2 groups. Group-I consists of 30 patients who have undergone embolization procedure with high density OnyxⓇ prior to radiosurgery whereas Group-II had 30 patients who did not have embolization. These plans were recalculated with MC algorithm while keeping parameters like beam orientation, multileaf collimator (MLC) positions, MLC margin, prescription dose, and monitor units constant. Several treatment coverage parameters, isodose volumes, plan quality metrics, dose to organs at risk, and integral dose were used for comparing the 2 algorithms. The isodose distribution generated by the 2 algorithms was also compared with gamma analysis using 1%/1 mm criterion. The difference between the 2 groups as well as the differences in dose calculation by PB and MC algorithms were tested for significance using independent t-test and paired t-test respectively at 5% level of significance. The results of the independent t-test showed that there is no significant difference between the Group-I and Group-II patients for PB as well as MC algorithm due to the presence of high density embolization material. However, results of the paired t-test showed that the differences between the PB and MC algorithms were significant for several parameters analyzed in both groups of patients. The gamma analysis results also showed differences in the dose calculated by the 2 algorithms especially in the low dose regions. The significant differences between the 2 algorithms are probably due to the incorrect representation of the loss of lateral charged particle equilibrium and lateral broadening of small photon beams by PB algorithm. MC algorithms are generally considered not essential for dose calculations for target volumes located in the brain. This study demonstrates PB algorithm may not be sufficiently accurate to predict dose distributions for small fields where there is loss of LCPE. The lateral broadening due to the loss of LCPE as predicted by the MC algorithm could be the main reason for significant differences in the parameters compared. Hence, an accurate MC algorithm if available may prove valuable for intracranial SRS treatment planning of such benign lesions where the long life expectancy of patients makes accurate dosimetry critical.

Cost determinants in management of brain arteriovenous malformations.

INTRODUCTION: There is little data on the cost of treating brain arteriovenous malformations (AVMs). The goal of this study then is to identify cost determinants in multimodal management of brain AVMs. METHODS: One hundred forty patients with brain AVMs prospectively enrolled in the UCSF brain AVM registry and treated between 2012 and 2015 were included in the study. Patient and AVM characteristics, treatment type, and length of stay and radiographic evidence of obliteration were collected from the registry. We then calculated the cost of all inpatient and outpatient encounters, interventions, and imaging attributable to the AVM. We used generalized linear models to test whether there was an association between patient and AVM characteristics, treatment type, and cost and length of stay. We tested whether the proportion of patients with radiographic evidence of obliteration differed between treatment modalities using Fisher's exact test. RESULTS: The overall median cost of treatment and interquartile range was $77,865 (49,566-107,448). Surgery with preoperative embolization was the costliest treatment at $91,948 (79,914-140,600), while radiosurgery was the least at $20,917 (13,915-35,583). In multi-predictor analyses, hemorrhage, Spetzler-Martin grade, and treatment type were significant predictors of cost. Patients who had surgery had significantly higher rates of obliteration compared with radiosurgery patients. CONCLUSIONS: Hemorrhage, AVM grade, and treatment modality are significant cost determinants in AVM management. Surgery with preoperative embolization was the costliest treatment and radiosurgery the least; however, surgical cases had significantly higher rates of obliteration.

The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?

BACKGROUND: The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial. OBJECTIVE: To confirm or repudiate the ARUBA conclusion that "medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations." METHODS: Data were collected from 1351 patients treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean 6.5). The results of the analyses were compared to that found in patients randomized to medical management only in the ARUBA trial and extrapolated to a 10-yr time period. Our data were also compared to the natural course in a virtual AVM population for a 25-yr time period. RESULTS: The incidence of stroke was similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer the follow-up, the relatively better outcome following treatment. Both the mortality rate and the incidence of permanent deficits in patients with small AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS, after which GKS patients did better. Patients with large AVMs had a higher incidence of neurological deficits in the first 3 yr following GKS. The difference decreased thereafter, but the time until break even depended on the analysis method used and the assumed risk for hemorrhage in patent AVMs. CONCLUSION: The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.

Reimagining ARUBA: Theoretical Optimization of the Treatment of Unruptured Brain Arteriovenous Malformations.

BACKGROUND AND PURPOSE: The results of the A Randomized Trial of Unruptured Brain Arteriovenous (ARUBA) study, indicating that conservative medical management of unruptured brain arteriovenous malformations (UBAVM) is superior to interventional therapy, have generated debates that have hampered their application into clinical practice. Irrespectively of study conclusions, it seems reasonable to explore how much better interventional therapy would have to be to become competitive with conservative medical management. METHODS: We conducted an exploratory analysis to replicate the original data from ARUBA. The functional form of the replicated ARUBA data, according to their Weibull distribution, allowed estimation of parameters. We carried out Monte Carlo simulations while introducing theoretical reductions of interventional risk, and the results were used to construct theoretical and example Kaplan-Meier curves from simulations. RESULTS: The "ARUBA Replication" analysis showed results nearly identical to those published in the study, with an estimated hazard ratio of 0.27 (95% CI: 0.14-0.55). At 50% interventional risk reduction, the simulations showed an estimated event rate of 14.9%, and the protective effect of conservative medical management was no longer statistically significant. Greater risk reductions hastened the time to benefit for interventional therapy, and an 80% risk reduction demonstrated superiority of interventional therapy at just over 2 years Hazard Ratio (HR: 1.44, 95% CI: 0.55-4.92). CONCLUSIONS: Reduction in risk of interventional therapy by 50%-80% results in more competitive clinical outcomes, equating or surpassing the benefit of conservative medical management of UBAVM. This conjecture should be taken into consideration in the design of future studies of this patient population, particularly because it is supported by recent observational studies.

Contralateral Transfalcine Versus Ipsilateral Anterior Interhemispheric Approach for Midline Arteriovenous Malformations: Surgical and Anatomical Assessment.

BACKGROUND: The contralateral anterior interhemispheric approach (CAIA) is considered to provide surgical advantages to access deep midline lesions: wider working angle, gravity enhanced dissection and retraction, more efficient lighting, and ergonomics. Our team has previously published on the merits of using a contralateral trajectory for medial frontoparietal arteriovenous malformations (AVMs) compared with the conventional anterior interhemispheric approach (IAIA). In this article, we compare the IAIA and CAIA for the resection of medial frontoparietal AVMs using quantitative surgical and anatomical analysis. METHODS: Two models were designed mimicking the most common features of midline AVMs. The CAIA and IAIA were performed bilaterally in 10 specimens. Variables to compare technical feasibility (surgical window [SW] and surgical freedom [SF], target exposure, and angle of attack) were independently assessed using stereotactic navigation. The average SW, SF, and angle of attack were compared with the Student t test. Significance threshold was set at 0.05. RESULTS: The CITA and IAIA were similar in terms of SW, target exposure, and SF in the superior aspect of the AVM. In the depth of the interhemispheric fissure, the CAIA was significantly superior to IAIA in both AVM models: 77% wider AA for the inferior aspect of the AVM (P < 0.01) and greater SF for the draining vein (54%, P = 0.01), ipsilateral (98%, P = 0.02), and contralateral ACA (117%, P < 0.01). CONCLUSIONS: This study suggests technical superiority of the CAIA for the resection of deep midline AVMs. No objective difference was noted in the superficial areas of our models, denoting that IAIA is a safer choice for superficial AVMs. Our results set the foundation for further clinical analysis comparing both approaches.

Predictors of Surgical Site Infection After Nonemergent Craniotomy: A Nationwide Readmission Database Analysis.

OBJECTIVE: Surgical site infections (SSIs) carry significant patient morbidity and mortality and are a major source of readmissions after craniotomy. Because of their deleterious effects on health care outcomes and costs, identifying modifiable risk factors holds tremendous value. However, because SSIs after craniotomy are rare and most existing data comprise single-institution studies with small sample sizes, many are likely underpowered to discern for such factors. The objective of this study was to use a large hetereogenous patient sample to determine SSI incidence after nonemergent craniotomy and identify factors associated with readmission and subsequent need for wound washout. METHODS: We used the 2010-2014 Nationwide Readmissions Database cohorts to discern for factors predictive of SSI and washout. RESULTS: We identified 93,920 nonemergent craniotomies. There were 2079 cases of SSI (2.2%) and 835 reoperations for washout (0.89%) within 30 days of index admission and there were 2761 cases of SSI (3.6%) and 1220 reoperations for washout (1.58%) within 90 days. Several factors were predictive of SSI in multivariate analysis, including tumor operations, external ventricular drain (EVD), age, length of stay, diabetes, discharge to an intermediate-care facility, insurance type, and hospital bed size. Many of these factors were similarly implicated in reoperation for washout. CONCLUSIONS: SSI incidence in neurosurgery is low and most readmissions occur within 30 days. Several factors predicted SSI after craniotomy, including operations for tumor, younger age, hospitalization length, diabetes, discharge to institutional care, larger hospital bed size, Medicaid insurance, and presence of an EVD. Diabetes and EVD placement may represent modifiable factors that could be explored in subsequent prospective studies for their associations with cranial SSIs.

Conventional digital subtractional vs non-invasive MR angiography in the assessment of brain arteriovenous malformation.

OBJECTIVES: Digital subtractional angiography (DSA) is the standard method for diagnosis, assessment and management of arteriovenous malformation in the brain. Conventional DSA (cDSA) is an invasive imaging modality that is often indicated before interventional treatments (embolization, open surgery, gamma knife). Here, we aimed to compare this technique with a non-invasive MR angiography (MRI DSA) for brain arteriovenous malformation (bAVM). PATIENTS AND METHODS: Fourteen patients with ruptured brain AVM underwent embolization treatment pre-operation. Imaging was performed for all patients using MRI (1.5 T). After injecting contrast Gadolinium, dynamic MRI was performed with 40 phases, each phase of a duration of 1.2 s and having 70 images. The MRI results were independently assessed by experienced radiologist blinded to the cDSA. RESULTS: The AVM nidus was depicted in all patients using cDSA and MRI DSA; there was an excellent correlation between these techniques in terms of the maximum diameter and Spetzler Martin grading. Of the fourteen patients, the drainage vein was depicted in 13 by both cDSA and MRI DSA showing excellent correlation between the techniques used. CONCLUSION: MRI DSA is a non-invasive imaging modality that can give the images in dynamic view. It can be considered as an adjunctive method with cDSA to plan the strategy treatment for bAVM.