巨大動静脈奇形（頚部顔面又は四肢病変）

Vascular anomalies, including proliferative vascular tumours and structural malformations, are largely driven by postzygotic somatic mutations that constitutively activate key signalling pathways, mainly the PI3K/AKT/mTOR and RAS/MAPK pathways. This molecular understanding has shifted clinical management from empiric interventions towards precision medicine. In this review, the interactions between somatic mosaicism, germline predispositions (e.g., PTEN hamartoma tumour syndrome), and microenvironmental risk factors in the context of lesional progression are described. We synthesized data on genotype‒phenotype correlations-such as PIK3CA mutations in lymphatic and venous malformations, KRAS/MAP2K1 mutations in arteriovenous malformations, and cerebral cavernous malformation (CCM) complex dysfunctions in cerebral cavernous anomalies-while fundamentally differentiating the mechanistic dependencies of true malformations from those of proliferative tumours. Targeted therapies, including mTOR, PI3Kα, and MEK inhibitors, have exhibited significant clinical efficacy in the treatment of pathway-specific anomalies. Despite these advances, therapeutic resistance and drug dependency persist. Future directions include the development of integrated diagnostic frameworks combining tissue biopsies with longitudinal cell-free DNA (cfDNA) monitoring, optimizing dual-pathway combination strategies, and advancing cellular models to reshape the management of vascular anomalies.

Cerebral arteriovenous malformations (cAVMs) are high-flow vascular lesions associated with a relevant risk of intracranial hemorrhage. Beyond angioarchitectural determinants, emerging evidence suggests that alterations of the internal elastic lamina (IEL) and elastic fiber network may contribute to vascular remodeling and structural instability. We conducted a structured qualitative literature review with narrative synthesis, without quantitative meta-analysis because of substantial methodological and biological heterogeneity across studies. We included histological, molecular, and genetic investigations addressing elastin biology, IEL structure, extracellular matrix remodeling, and related signaling pathways in cAVMs within the broader context of vascular wall biology. Twenty studies met the predefined inclusion criteria. Direct histopathological evidence of IEL fragmentation was identified in only two primary studies, whereas additional histological investigations reported structural abnormalities including IEL disorganization, interruption, or irregular thickening. Molecular studies consistently described dysregulation of KRAS-MAPK, Notch, and BMP9/ALK1 signaling pathways involved in vascular endothelial homeostasis and extracellular matrix remodeling, although most did not directly evaluate IEL or elastic fiber architecture. Collectively, these findings support biologically plausible mechanisms of vascular remodeling rather than a unified mechanistic cascade. Similarities with inherited disorders affecting elastogenesis represent mechanistic analogies rather than evidence of shared disease pathogenesis. Alterations of the IEL and elastic fiber network may represent a relevant component of the structural phenotype of cAVMs, potentially acting as downstream or parallel manifestations within a multifactorial biological framework. Integrating histopathological and molecular evidence may improve the biological characterization of these lesions and support future hypothesis generation regarding vascular stability. However, the currently available evidence does not allow causal inference regarding the role of IEL alterations or elastic fiber disruption in cAVM pathogenesis or rupture susceptibility.

BACKGROUND: Brain arteriovenous malformations (AVMs) with high-risk angioarchitecture features are associated with the risk of hemorrhage. This study evaluated the safety and effectiveness of a combined approach involving targeted embolization of high-risk components and stereotactic radiosurgery (SRS). METHODS: This single-center retrospective study included 17 consecutive patients with 17 AVMs with high-risk components who underwent targeted embolization and SRS. Technical success, procedural complications, obliteration rates, and hemorrhage during the latency period were assessed. RESULTS: Of the total, 15 (88%) patients had a history of AVM rupture. Target embolization using liquid embolic material was successful in 16 (94%) patients, with minimal embolization of the nidus (median, 2.8%). Complications related to embolization occurred in three (17.6%) patients, with only one (5.9%) experiencing a minor persistent deficit. Among the 14 patients with >1 year follow-up (median 60 months), complete AVM obliteration was confirmed in 9 (64%) patients, and the cumulative obliteration rates at 3, 5, and 7 years after SRS were 35%, 54%, and 85%, respectively. Target embolization was unsuccessful in one patient (5.9%), who experienced hemorrhage during the latency period. One bleeding event occurred during the latency period (1/17, 5.9%). CONCLUSIONS: MTE combined with SRS may represent a feasible strategy for morphologically high-risk brain AVMs, with the potential to reduce latency-period hemorrhage without clearly compromising nidus obliteration. However, given the small cohort and lack of a control group, the observed reduction in hemorrhage risk should be interpreted cautiously. These findings support the value of this approach as a proof-of-concept, but further prospective studies with larger cohorts are needed to confirm its clinical benefit.

Gould syndrome, caused by COL4A1/COL4A2 mutations, is a rare multisystem disorder characterized by basement membrane defects leading to vascular fragility, cerebral small vessel disease, seizures, and renal involvement. While vascular complications are well-described, gastrointestinal bleeding remains exceedingly rare. We describe a four-year-old female with a known diagnosis of Gould syndrome who presented with hemodynamically significant hematochezia. Colonoscopy demonstrated tortuous submucosal vascular lesions consistent with colonic varices in the sigmoid colon, which were treated with bipolar probe electrocautery; an additional non-bleeding varix was noted at the hepatic flexure. Computed tomography (CT) angiography and time-resolved imaging of contrast kinetics magnetic resonance imaging (TRICKS MRI) revealed abnormal venous structures in the mesentery and bowel without evidence of arteriovenous malformation or portal-systemic shunting, congruent with endoscopic findings. There was no clinical or radiographic evidence of portal hypertension. This case expands the phenotypic spectrum of Gould syndrome by providing detailed evidence of gastrointestinal venous abnormalities and highlights gastrointestinal bleeding as a potential underrecognized manifestation of COL4A1/2-related disease.

PURPOSE: Radiation therapy is a well-established treatment method for cerebral arteriovenous malformations (AVMs) used in combination with other treatment modalities or alone. This study evaluated the postintervention bleeding risk of cerebral AVMs treated with stereotactic radiosurgery (SRS) using a linear accelerator (LINAC) and identified predictors of posttherapeutic hemorrhage. METHODS AND MATERIALS: A retrospective analysis was conducted on 134 consecutive patients with AVMs treated with LINAC-based SRS between 1983 and 2022 at the department for Radiotherapy and Radiation Oncology at the Marburg University Hospital. Patients were followed for a median of 49 months. Statistical analysis was performed to assess the influence of variables such as AVM grade, prior treatment, SRS dose, and other clinical factors on post-SRS bleeding risk. RESULTS: Nine post-SRS hemorrhages occurred for a total of 816.6 patient-years, resulting in an overall bleeding rate of 6.7% and an annual rate of 1.1%. No bleeding-related fatalities were recorded. Higher Spetzler-Martin AVM grade (P = .013) and prior treatment, particularly embolization or the combination of surgery and embolization (P = .005), were associated with increased posttherapeutic hemorrhage risk. In contrast, factors such as age, sex, and SRS dose showed no significant influence. Two bleeding events occurred even after presumed angiographic obliteration. CONCLUSION: LINAC-based SRS for AVMs is associated with with a relatively low risk of posttreatment hemorrhage, with an annual bleeding rate lower than that of untreated AVMs and comparable with the risk found in previous studies. Higher AVM grades and prior treatments are key predictors of post-SRS hemorrhage. Given the possibility of hemorrhage even after angiographic obliteration, close long-term follow-up is recommended. Modern imaging techniques may enhance postobliteration monitoring in high-risk cases.