Enhancing the quality of evidence, comparability, and reproducibility in brain arteriovenous malformations treated with open surgery research: a systematic review and proposal of a reporting guideline for surgical and clinical outcomes.

Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

The role of surgical disconnection for posterior fossa pial arteriovenous fistulas and dural fistulas with pial supply: an illustrative case series.

BACKGROUND: Pial arteriovenous fistulas (pAVFs) are rare vascular malformations characterized by high-flow arteriovenous shunting involving a cortical arterial supply directly connecting to venous drainage without an intermediate nidus. Dural arteriovenous fistulas (dAVFs) can infrequently involve additional pial feeders which can introduce higher flow shunting and increase the associated treatment risk. In the posterior fossa, arteriovenous fistula (AVF) angioarchitecture tends to be particularly complex, involving either multiple arterial feeders-sometimes from both dural and pial origins-or small caliber vessels that are difficult to catheterize and tend to be intimately involved with functionally critical brainstem or upper cervical cord structures. Given their rarity, published experience on microsurgical or endovascular treatment strategies for posterior fossa pAVFs and dAVFs with pial supply remains limited. METHODS: Retrospective chart review from 2019-2023 at a high-volume center identified six adult patients with posterior fossa pAVFs that were unable to be fully treated endovascularly and required microsurgical disconnection. These cases are individually presented with a technical emphasis and supported by comprehensive angiographic and intraoperative images. RESULTS: One vermian (Case 1), three cerebellopontine angle (Cases 2-4) and two craniovertebral junction (Cases 5-6) posterior fossa pAVFs or dAVFs with pial supply are presented. Three cases involved mixed dural and pial arterial supply (Cases 1, 4, and 6), and one case involved a concomitant microAVM (Case 2). Endovascular embolization was attempted in four cases (Cases 1-4): The small caliber and tortuosity of the main arterial feeder prevented catheterization in two cases (Cases 1 and 3). Partial embolization was achieved in Cases 2 and 4. In Cases 5 and 6, involvement of the lateral spinal artery or anterior spinal artery created a prohibitive risk for endovascular embolization, and surgical clip ligation was pursued as primary management. In all cases, microsurgical disconnection resulted in complete fistula obliteration without evidence of recurrence on follow-up imaging (mean follow-up 27.1 months). Two patients experienced persistent post-treatment sensory deficits without significant functional limitation. CONCLUSIONS: This illustrative case series highlights the technical difficulties and anatomical limitations of endovascular management for posterior fossa pAVFs and dAVFs with pial supply and emphasizes the relative safety and utility of microsurgical disconnection in this context. A combined approach involving partial preoperative embolization-when the angioarchitecture is permissive-can potentially decrease surgical morbidity. Larger studies are warranted to better define the role for multimodal intervention and to assess associated long-term AVF obliteration rates in the setting of pial arterial involvement.

Fractal-Based Analysis of Arteriovenous Malformations (AVMs).

Arteriovenous malformations (AVMs) are cerebrovascular lesions consisting of a pathologic tangle of the vessels characterized by a core termed the nidus, which is the "nest" where the fistulous connections occur. AVMs can cause headache, stroke, and/or seizures. Their treatment can be challenging requiring surgery, endovascular embolization, and/or radiosurgery as well. AVMs' morphology varies greatly among patients, and there is still a lack of standardization of angioarchitectural parameters, which can be used as morphometric parameters as well as potential clinical biomarkers (e.g., related to prognosis).In search of new diagnostic and prognostic neuroimaging biomarkers of AVMs, computational fractal-based models have been proposed for describing and quantifying the angioarchitecture of the nidus. In fact, the fractal dimension (FD) can be used to quantify AVMs' branching pattern. Higher FD values are related to AVMs characterized by an increased number and tortuosity of the intranidal vessels or to an increasing angioarchitectural complexity as a whole. Moreover, FD has been investigated in relation to the outcome after Gamma Knife radiosurgery, and an inverse relationship between FD and AVM obliteration was found.Taken altogether, FD is able to quantify in a single and objective value what neuroradiologists describe in qualitative and/or semiquantitative way, thus confirming FD as a reliable morphometric neuroimaging biomarker of AVMs and as a potential surrogate imaging biomarker. Moreover, computational fractal-based techniques are under investigation for the automatic segmentation and extraction of the edges of the nidus in neuroimaging, which can be relevant for surgery and/or radiosurgery planning.

[Presurgical Simulation for Brain Arteriovenous Malformation].

Surgical extirpation of brain arteriovenous malformations(AVMs)requires precise pre-surgical simulation. Utilizing image software, widely used with picture archiving and communication systems(PACS), surgeons can generate simulation images that precisely illustrate the proper feeders, passing arteries, and drainers. The crucial steps for creating informative simulation images include: (1)the free rotation of reconstructed 3D digital subtraction angiography(DSA)images; (2)removal of irrelevant arteries(the most important procedure); and(3)construction of stereo imagery of the "core images." This article presents a detailed description of these procedures.

Stereotactic radiosurgery with versus without embolization for intracranial dural arteriovenous fistulas: a systematic review and meta-analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been established as a safe and alternative treatment for dural arteriovenous fistulas (dAVFs). While embolization alone is the most commonly used modality for the treatment of dAVFs, the adjunctive use of embolization with SRS, with the growing use of SRS, has gained increasing interest in the past few years. However, the relative efficacy and safety of SRS combined with embolization versus SRS alone for dAVFs remains uncertain. Hence, this systematic review aimed to evaluate the efficacy of SRS with adjunctive embolization for intracranial dAVFs. METHODS: A systematic review and meta-analysis was conducted by searching electronic databases, including PubMed, Embase, and the Cochrane Library, up to August 2023. All studies evaluating the utilization of adjunctive embolization and SRS for dAVFs were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on the suitable outcomes. RESULTS: Eighteen studies involving 715 patients were included. The mean age of the participants in the study was 64.30 years in the adjunctive embolization group and 60.51 years in the SRS-alone group. In the adjunctive embolization group 41.3% of patients were female, compared with 47.1% in the SRS-only group. The dAVF obliteration rates were 64.7% and 65.7% in the adjunctive embolization and SRS-alone groups, respectively. These obliteration rates were comparable between the two groups (p = 0.96), as were the symptom improvement rates (p = 0.35). Adverse events were rare, and were more commonly associated with the adjunctive embolization procedure, although further causal analysis was not possible. CONCLUSIONS: This study provides evidence that adjunctive embolization plus SRS provides similar obliteration and symptom improvement rates compared with SRS alone, with both having very limited SRS-related adverse events. Considering the added burden and adverse events of additional endovascular treatment, the authors recommend embolization be reserved for more complex dAVFs or when embolization can potentially be curative alone or provide more rapid symptomatic relief or protection during the radiosurgical latency period.

Coexistence of moyamoya syndrome with arteriovenous malformation. Systematic review and illustrative case report.

The coexistence of Moyamoya Syndrome with Arteriovenous Malformation is exceedingly rare. Here, we present the case of a 37-year-old female patient diagnosed with AVM in the right parietal lobe, accompanied by severe stenosis of the right middle cerebral artery and right anterior cerebral artery, along with moyamoya collateral induction. Our objective was to investigate the frequency and mutual influence of these conditions, and to determine a preferable treatment strategy by conducting a comprehensive review of previous case reports. We conducted a thorough search of PubMed, Scopus, and Web of Science databases, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our review encompassed 36 publications, reporting a total of 64 cases of AVM coexisting with Moyamoya Syndrome. Notably, bilateral stenosis was observed in half of the cases. Among patients with unilateral stenosis, AVM was localized in the opposite hemisphere only in 2 cases. Treatment approaches varied, with 18 cases undergoing active treatment for both stenosis and AVM, 11 cases treating stenosis prior to AVM, 5 cases addressing AVM first, and 3 cases treating both AVM and stenosis simultaneously. Embolization, either standalone or supplemented by stereotactic radiosurgery, was employed in six cases. Stereotactic radiosurgery alone was utilized in 12 cases, while 15 patients underwent surgical removal of the AVM. Our findings provide valuable insights for neurosurgeons managing patients with concurrent AVM and Moyamoya Syndrome. The variety of treatment approaches observed in the literature underscores the complexity of these cases, emphasizing the need for individualized strategies. This information may guide future systematic reviews and meta-analyses, contributing to a better understanding of the optimal management of these rare coexisting vascular pathologies.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Mixed reality in neurosurgery: redefining the paradigm for arteriovenous malformation planning and navigation to improve patient outcomes.

OBJECTIVE: Brain arteriovenous malformations (AVMs) present significant challenges in neurosurgery, requiring detailed planning and execution. In this study, the authors aimed to evaluate the efficacy of mixed reality (MxR), a synergistic application of virtual reality (VR) and augmented reality (AR), in the surgical management of AVMs. METHODS: A retrospective review was conducted on 10 patients who underwent AVM resection between 2021 and 2023. Preoperative planning used patient-specific 360° VR models, while intraoperative guidance used AR markers for targeted disconnection of arterial feeders. Data were analyzed for surgical duration, blood loss, and postoperative outcomes, stratified by Spetzler-Martin (SM) and supplemented Spetzler-Martin (Supp-SM) grades. RESULTS: In 10 patients with cerebral AVMs, MxR significantly facilitated the identification of 21 arterial feeders, including challenging deep feeders. MxR-assisted surgeries demonstrated efficient identification and disconnection of arterial feeders, contributing to precise AVM resection. The mean surgical duration was approximately 5 hours 11 minutes, with a mean intraoperative blood loss of 507.5 ml. Statistically significant variations in surgical duration and blood loss were observed based on SM and supplemented Supp-SM grades. Two patients experienced worsened postoperative neurological deficits, underscoring the inherent risks of AVM surgeries. The marked difference in hospital stays between patients with ruptured and those with unruptured AVMs, particularly for SM grade III, highlights the significant impact of rupture status on postoperative recovery. CONCLUSIONS: In this study, the authors delineated a novel paradigm using MxR for the surgical intervention of AVMs. Using 3D VR for preoperative planning and AR for intraoperative guidance, they achieved unparalleled precision and efficiency in targeting deep arterial feeders. While the results are promising, larger studies are needed to further validate this approach.

Brain AVM surgery without endovascular embolization in a low to middle income country.

We treated a 20-year-old woman in Paraguay with a ruptured intraventricular Spetzler-Martin Grade 3 AVM, and illustrate microsurgical resection without embolization in this video.

Comprehensive neurosurgical treatment of right occipital arteriovenous malformation with advanced angiographic techniques.

/Summary. A 39-year-old female with a notable medical history of smoking and a familial predisposition to unruptured aneurysms presented with clinical symptoms of intermittent right-sided headaches, flashes of light, and pulsatile tinnitus in the right ear. Diagnostic evaluations, including advanced angiographic techniques, identified a right occipital arteriovenous malformation (AVM). The angiogram revealed significant venous flow voids, emphasizing the need for a comprehensive treatment approach. The Spetzler-Martin grading system classified the AVM as Grade 2, indicating a moderate risk profile. A strategic decision was made to undergo partial embolization of two primary arterial feeders from the right posterior cerebral artery (PCA). Subsequent post-embolization angiograms confirmed a marked reduction in arteriovenous shunting, validating the efficacy of the intervention. The surgical approach encompassed an occipital craniotomy, meticulous subarachnoid dissection, and intraoperative angiography to ensure complete resection. Post-operative assessments showcased a successful and complete AVM resection. The patient experienced a brief, transient headache post-surgery, which resolved on its own. She was discharged on the third post-operative day and has since reintegrated into her professional life. However, she reported a minor visual field deficit, which, while noticeable, did not impede her daily activities. This case underscores the importance of a holistic, patient-centric approach in managing AVMs [1-3]. It challenges the conventional wisdom from the ARUBA trial, advocating for a more nuanced, individualized treatment paradigm, especially for young patients with low-grade AVMs [4].

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.

A Review of Preoperative Embolization Effectiveness in Patients With Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Preoperative embolization of arteriovenous malformations (AVMs) remains controversial. This study sought to analyze the cost-effectiveness of preoperative embolization of AVMs. METHODS: Patients who underwent AVM resection at a single institute (January 1, 2015-December 31, 2020) were analyzed. Patients with preoperative embolization (embolization cohort) were compared with those without preoperative embolization (nonembolization cohort). Cost-effectiveness score (CE) was the primary outcome of interest and was determined by dividing the total 1-year cost by effectiveness, which was derived from a validated preoperative to last follow-up change in the modified Rankin Scale utility score. A lower CE signifies a more cost-effective treatment strategy. RESULTS: Of 188 patients, 88 (47%) underwent preoperative embolization. The mean (SD) total cost was higher in the embolization group than in the nonembolization group ($117 594 [$102 295] vs $84 348 [$82 326]; P < .001). The mean (SD) CE was higher in the embolization cohort ($336 476 [$1 303 842]) than in the nonembolization cohort ($100 237 [$246 255]; P < .001). Among patients with Spetzler-Martin (SM) grade I and II AVMs, the mean (SD) CE was higher in the embolization (n = 40) than in the nonembolization (n = 72) cohort ($164 950 [$348 286] vs $69 021 [$114 938]; P = .004). Among patients with SM grade III AVMs, the mean (SD) CE was lower in the embolization (n = 33) than in the nonembolization (n = 25) cohort ($151 577 [$219 130] vs $189 195 [$446 335]; P = .006). The mean (SD) CE was not significantly different between cohorts among patients with higher-grade AVMs (embolization cohort [n = 3] vs nonembolization cohort [n = 15]: $503 639 [$776 492] vs $2 048 419 [$4 794 758]; P = .49). The mean CE for embolized SM grade III aneurysms was nonsignificant in the ruptured group; however, for the unruptured group, CE was significantly higher in the embolization cohort (n = 26; $160 871 [$240 535]) relative to the nonembolization cohort (n = 15; $108 152 [$166 446]) ( P = .006). CONCLUSION: Preoperative embolization was cost-effective for patients with SM grade III AVMs but not for patients with lower-grade AVMs.

Giant Brain Arteriovenous Malformation Managed by Staged Embolizations and Surgical Resection with Satisfactory Outcome.

Spetzler-Martin grade V (>6 cm) arteriovenous malformations (AVMs) are traditionally considered inoperable. A 35-year-old man presented with repeated seizures for 7 years, and computed tomography arteriography and magnetic resonance imaging revealed left deep hemispheric AVM. A combination of embolization and surgical resection successfully achieved a cure of the patient. Well-equipped neurosurgery facilities can best manage selective Spetzler-Martin grade V AVMs with no neurologic deficits contrary to their traditionally inoperable concept. Successful surgery offers the patient a better quality of life.

Radiosurgery With Prior Embolization Versus Radiosurgery Alone for Intracranial Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The addition of adjuvant embolization to radiosurgery has been proposed as a means of improving treatment outcomes of intracranial arteriovenous malformations (AVMs). However, the relative efficacy and safety of radiosurgery with adjuvant embolization vs radiosurgery alone remain uncertain. Moreover, previous systematic reviews and meta-analyses have included a limited number of studies and did not consider the effects of baseline characteristics, including AVM volume, on the outcomes. This systematic review aimed to evaluate the efficacy of preradiosurgery embolization for intracranial AVMs with consideration to matching status between participants in each treatment group. METHODS: A systematic review and meta-analysis were conducted by searching electronic databases, including PubMed, Scopus, and Cochrane Library, up to January 2023. All studies evaluating the utilization of preradiosurgery embolization were included. RESULTS: A total of 70 studies (9 matched and 71 unmatched) with a total of 12 088 patients were included. The mean age of the included patients was 32.41 years, and 48.91% of the patients were female. Preradiosurgery embolization was used for larger AVMs and patients with previous hemorrhage ( P < .01, P = .02, respectively). The obliteration rate for preradiosurgery embolization (49.44%) was lower compared with radiosurgery alone (61.42%, odds ratio = 0.56, P < .01), regardless of the matching status of the analyzed studies. Although prior embolization was associated higher rate of cyst formation ( P = .04), it lowered the odds of radiation-induced changes ( P = .04). The risks of minor and major neurological deficits, postradiosurgery hemorrhage, and mortality were comparable between groups. CONCLUSION: This study provides evidence that although preradiosurgery embolization is a suitable option to reduce the AVM size for future radiosurgical interventions, it may not be useful for same-sized AVMs eligible for radiosurgery. Utilization of preradiosurgery embolization in suitable lesions for radiosurgery may result in the added cost and burden of an endovascular procedure.

Management outcomes of peripontine arteriovenous malformation patients presenting with trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia as the presenting symptom of brain arteriovenous malformation (bAVM) has been rarely reported. Treatment of reported cases has been skewed toward surgery for these scarce, deeply located bAVMs. Here, the authors report their management and outcomes of bAVM patients presenting with ipsilateral trigeminal neuralgia (TN) at their institution. METHODS: This is a retrospective cohort study. The authors' institutional bAVM database was queried for non-hereditary hemorrhagic telangiectasia bAVMs in pontine, cistern, brainstem, trigeminal nerve, or tentorial locations. Patients with complete data were included in a search for trigeminal neuralgia or "facial pain" as the presenting symptom with TN being on the same side as the bAVM. Demographics, TN and bAVM characteristics, management strategies, and outcomes of bAVM and TN management were analyzed. RESULTS: Fifty-seven peripontine bAVMs were identified; 8 (14.0%) of these bAVMs were discovered because of ipsilateral TN, including 4 patients (50%) with facial pain in the V2 distribution. Five patients (62.5%) were treated with carbamazepine as the initial medical therapy, 2 (25%) underwent multiple rhizotomies, and 1 (12.5%) underwent microvascular decompression. None of the patients with TN-associated bAVMs presented with hemorrhage, compared with 25 patients (51%) with bAVMs that were not associated with TN (p < 0.01). TN-associated bAVMs were overall smaller than non-TN-associated bAVMs, but the difference was not statistically significant (1.71 cm vs 2.22 cm, p = 0.117), and the Spetzler-Martin grades were similar. Six patients (75%) underwent radiosurgery to the bAVM (mean dose 1800 cGy, mean target volume 0.563 cm3) and had complete resolution of TN symptoms (100%). The mean time from radiosurgery to TN resolution was 193 (range 21-360) days, and 83.3% of treated TN-associated bAVMs were obliterated via radiosurgery. Two patients (12.5%) were recommended for conservative management, with one undergoing subsequent rhizotomies and another patient died of hemorrhage during follow-up. CONCLUSIONS: TN-associated bAVM is a rare condition with limited evidence for management guidance. Radiosurgery can be safe and effective in achieving durable TN control in patients with TN-associated bAVMs. Despite their deep location and unruptured presentation, obliteration can reach 83.3% with radiosurgery.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/ß ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). RESULTS: One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). CONCLUSION: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Deep Learning Detection and Segmentation of Brain Arteriovenous Malformation on Magnetic Resonance Angiography.

BACKGROUND: The delineation of brain arteriovenous malformations (bAVMs) is crucial for subsequent treatment planning. Manual segmentation is time-consuming and labor-intensive. Applying deep learning to automatically detect and segment bAVM might help to improve clinical practice efficiency. PURPOSE: To develop an approach for detecting bAVM and segmenting its nidus on Time-of-flight magnetic resonance angiography using deep learning methods. STUDY TYPE: Retrospective. SUBJECTS: 221 bAVM patients aged 7-79 underwent radiosurgery from 2003 to 2020. They were split into 177 training, 22 validation, and 22 test data. FIELD STRENGTH/SEQUENCE: 1.5 T, Time-of-flight magnetic resonance angiography based on 3D gradient echo. ASSESSMENT: The YOLOv5 and YOLOv8 algorithms were utilized to detect bAVM lesions and the U-Net and U-Net++ models to segment the nidus from the bounding boxes. The mean average precision, F1, precision, and recall were used to assess the model performance on the bAVM detection. To evaluate the model's performance on nidus segmentation, the Dice coefficient and balanced average Hausdorff distance (rbAHD) were employed. STATISTICAL TESTS: The Student's t-test was used to test the cross-validation results (P < 0.05). The Wilcoxon rank test was applied to compare the median for the reference values and the model inference results (P < 0.05). RESULTS: The detection results demonstrated that the model with pretraining and augmentation performed optimally. The U-Net++ with random dilation mechanism resulted in higher Dice and lower rbAHD, compared to that without that mechanism, across varying dilated bounding box conditions (P < 0.05). When combining detection and segmentation, the Dice and rbAHD were statistically different from the references calculated using the detected bounding boxes (P < 0.05). For the detected lesions in the test dataset, it showed the highest Dice of 0.82 and the lowest rbAHD of 5.3%. DATA CONCLUSION: This study showed that pretraining and data augmentation improved YOLO detection performance. Properly limiting lesion ranges allows for adequate bAVM segmentation. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Natural History and Histopathology of Expanding Cysts and Hematomas After Stereotactic Radiosurgery for Arteriovenous Malformations of the Brain: A Case Series.

BACKGROUND: We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. RESULTS: Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. CONCLUSIONS: Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.

Early experience of thalidomide therapy for high-grade peripheral and facial arteriovenous malformations.

BACKGROUND: Arteriovenous malformations (AVMs) are developmental defects in the vascular system with abnormal connections between arteries and veins. A minority of AVMs are characterized by aggressive growth and continue to proliferate despite maximal surgical and interventional therapy. We report our outcomes with the use of thalidomide as the only UK specialist center adopting this novel approach for the management of AVMs refractory to conventional therapy. METHODS: This was a retrospective case series which included only complex and proliferative AVM lesions (Schobinger grade III and IV). All patients prescribed thalidomide on a compassionate basis between September 2006 and August 2022 after attempts at embolosclerotherapy without satisfactory response were reviewed. RESULTS: Eleven patients were included in our study. The median total duration of thalidomide use was 10 months. Two thirds of patients with pain (six of nine) reported an improvement, three quarters reported a reduction in swelling (six of eight) and all who presented with bleeding reported improvement in overall volume or frequency (four of four). Over the study period, 45% achieved a non-proliferative state with no further target vessel demonstrable on angiography. Mild, tolerable side effects such as fatigue were common (73%). There was only one major adverse reaction (neutropenia) necessitating cessation of therapy. CONCLUSIONS: We can conclude that thalidomide is able to reduce the symptom burden for patients with complex and proliferative AVMs that were refractory to established treatment modalities. Adverse effects are common, but the benefit achieved from taking thalidomide in otherwise treatment resistant cases outweighs the risks, most of which are manageable.