Delayed versus immediate intervention of ruptured brain arteriovenous malformations:A case report

BACKGROUND Brain arteriovenous malformations(bAVMs)remains one of the most prevalent causes of intracranial hemorrhage and stroke-like syndromes in the young adult population.Although it has been agreed upon that definitive treatment using either single or multi-modal approach is warranted for successful bAVM management,much debate still revolves regarding the optimal timing of definitive treatment.CASE SUMMARY In this report,we present a case of delayed,definitive endovascular treatment for ruptured bAVM in a 21-year-old female,3 mo post-ictus.The bAVM,with a left pericallosal feeding artery and cortical draining veins,was successfully obliterated through embolization using the Onyx 18.On follow-up the patient has recommenced her daily activities and experiences only mild occasional headaches with mild motor deficits.The report leads to our review on an important issue regarding the optimal timing of ruptured bAVM definitive management and bring forward the current evidence available on delayed vs immediate definitive bAVM intervention.We also highlight current issues that need to be addressed for clearer guidelines on definitive therapy initiation.CONCLUSION Current treatment paradigms of ruptured bAVM remains elusive,with substantial heterogeneity in the current literature.A consensus on the definition of“acute”vs“delayed”,management goal,follow-up length and outcome parameters are required to support formation of a clear paradigm.

Overview of peripheral arteriovenous malformations:From diagnosis to treatment methods

Based on the latest classification by the International Society for the Study of Vascular Anomalies in 2018,vascular malformations(VMs)can be categorized into simple,combined,VMs of major named vessels,and VMs associated with other anomalies.Simple VMs include lymphatic,venous,capillary,and arteriovenous malformations(AVMs).AVMs represent disorders of direct arteriovenous shunts caused by the absence of a capillary bed between the involved arteries and veins.This abnormal vascular communication causes arterial blood to accumulate in the venous vessels,thus resulting in venous hypertension and characteristic clinical manifestations,such as pulsation,tremors,and elevated temperature.AVMs can occur sporadically or as manifestations of syndromic lesions and are considered among the most complex and challenging VMs.The diagnosis and treatment of AVMs can vary depending on the lesion location and associated clinical symptoms,thus complicating their management.Herein,we discuss peripheral AVMs in terms of their clinical manifestations,imaging examinations,and staging systems to provide a comprehensive reference for the treatment,evaluation methods,and follow-up procedures for this vascular anomaly.

Embolization of brain arteriovenous malformations with squid co-polymer embolic material:Initial experience

Objective:To analyze the safety and effectiveness of the ethylene-vinyl alcohol copolymer(EVOH)liquid embolic agent Squid(Emboflu,Switzerland)for the treatment of brain arteriovenous malformations.Materials and procedures:Between April 2015 and July 2017,46 embolization treatments for brain arteriovenous malformations(BAVM)were performed in 25 patients using two Squid formulations(18 and 12).Six female and 19 male patients with a mean age of 34 years(range,9–62 years)were included.A total of 46 procedures were performed.The BAVMs were classified as Spetzler-Martin gradeⅡin 4 procedures,Ⅲin 27 procedures,and 1V in 15 procedures.Among the 25 patients,15 presented with hemorrhage,5 with seizures,and 5 with headache and neurology.The BAVMs were located in the temporal lobe in 5 patients,parietal lobe in 7 patients,frontal lobe in 3 patients,posterior fossa in 6 patients,basal ganglia in 3 patients,and parasagittal lobe in 1 patient.Results:The obliteration rate of the BAVMs ranged from 10%to 100%,with a mean of 33%.Most patients underwent their first or second embolization procedure.Four patients(8%)developed intracranial bleeding post procedure,with one death(2%).One patient(2%)experienced a seizure during the procedure;however,no intracranial bleeding was observed.Seven patients(15%)experienced perforations during catheter manipulation.One case(2%)of fractured catheter was recorded,but no significant complications were observed.The average volume of copolymer injected was 0.6 ml per nidus.Thirteen procedures used the Squid-12 formulation,29 procedures used the Squid-18 formulation,and 3 procedures used a combination of Squid-12 and-18 formulations.Conclusion:Squid is a safe and effective embolic agent for treating BAVMs.

Pancreatic arteriovenous malformation treated with transcatheter arterial embolization:Two case reports and review of literature

BACKGROUND Various treatment methods are available for the treatment of pancreatic arteriovenous malformation(P-AVM);however,there are no established treatment options for asymptomatic P-AVM.CASE SUMMARY A 47-year-old and a 50-year-old male patients sought treatment for P-AVM in the pancreas,which was incidentally detected during routine abdominal computed tomography and magnetic resonance imaging conducted as part of a health check-up.They underwent transcatheter arterial embolization(TAE),and over the course of a 9-year follow-up period,the AVM did not worsen and was asymptomatic.CONCLUSION TAE can be considered as an alternative treatment option for P-AVM in selective cases where patients are asymptomatic or have a high surgical risk.

MEK inhibitors for the treatment of extracranial arteriovenous malformations

Arteriovenous malformations(AVMs)are serious congenital vascular anomalies in which the arteries connect directly with veins without capillaries.This condition will continue to worsen without proper intervention and cause ulcers,repeated hemorrhages,and even cardiac insufficiency.Primary treatment options for AVMs include surgery and interventional treatment;however,they are associated with high risk and recurrence rates.Recent studies revealed that excessive activation of the Ras/MAPK pathway can induce the formation and development of peripheral AVM,whereas MEK inhibitors can effectively control nidus progression,making them a potential novel treatment for AVM.This review provides an up-to-date overview of correlated laboratory and clinical research to provide information for further research and clinical practice.

Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques:A case report

BACKGROUND This case report demonstrates the simultaneous development of a gastrointestinal stromal tumour(GIST)with arteriovenous malformations(AVMs)within the jejunal mesentery.A 74-year-old male presented to the department of surgery at our institution with a one-month history of abdominal pain.Contrast-enhanced computed tomography revealed an AVM.During exploratory laparotomy,hyperspectral imaging(HSI)and indocyanine green(ICG)fluorescence were used to evaluate the extent of the tumour and determine the resection margins.Intraoperative imaging confirmed AVM,while histopathological evaluation showed an epithelioid,partially spindle cell GIST.CASE SUMMARY This is the first case reporting the use of HSI and ICG to image GIST intermingled with an AVM.The resection margins were planned using intraoperative analysis of additional optical data.Image-guided surgery enhances the clinician’s knowledge of tissue composition and facilitates tissue differentiation.CONCLUSION Since image-guided surgery is safe,this procedure should increase in popularity among the next generation of surgeons as it is associated with better postoperative outcomes.

Absolute ethanol embolization for treatment of peripheral arteriovenous malformations

Arteriovenous malformations(AVMs)are aggressive congenital high-flow vascular anomalies,in which the feeding artery and draining vein are connected through fistulas without normal capillary networks.In severe cases,the condition may cause swelling,ulceration,bleeding,and even heart failure.Various treatment options are available for AVMs,including laser,surgical resection,embolization,and targeted drug therapy.With the development of endovascular treatment technology,absolute ethanol embolization of AVMs has become one of the first-line therapies owing to its sustained efficacy and low recurrence rate.However,administration of this therapy is challenging and may lead to serious complications if inappropriately managed.In this article,we reviewed and summarized previous clinical articles,literature reviews,and clinical trial data to comprehensively describe clinical manifestations of AVMs,the mechanism of ethanol embolotherapy,key points in treatment and management of complications,and issues that need to be addressed.We expect to provide a reliable information reference source for clinical physicians and researchers.

A Rare Case: Multiple Mandibular Arteriovenous Malformation with High Output: May a Tooth Extraction Alone Turn to a Catastrophic Condition?

Background: Arteriovenous malformations (AVM) in mandible and neck are potentially life-threatening conditions because of possible massive hemorrhage. They are often first diagnosed by dentists as bleeding. In this case, we report how a tooth extraction turned to a catastrophic condition in a patient with multiple AVMs in the mandibular, submandibular and hyoid region. Case: A 19-year-old male patient diagnosed with AVMs in the mandibular and submandibular regions was admitted to our hospital with the complaint of leaky hemorrhage around the lower left 3rd molar tooth. Tooth extraction was planned after embolization procedure. The patient was intubated uneventfully using video laryngoscope. However, an acute bleeding of more than 1600 ml occurred in one minute just after the mouth opener was inserted. The patient was transferred to the Interventional Radiology and other branches of the high-flow AVM were embolized. The patient was taken back to the operating room and the tooth was extracted uneventfully. Conclusion: In AVM cases, trauma should be minimized during induction of general anesthesia and intubation should be performed gently with fiberoptic bronchoscopy or video laryngoscopy. We conclude that a multidisciplinary approach as applied to our patient would be valuable in such cases.

Natural history of inferior mesenteric arteriovenous malformation that led to ischemic colitis: A case report

BACKGROUND Ischemic colitis with inferior mesenteric arteriovenous malformation(AVM)is a rare disease.Although a few reports have been published,no report has described the natural history of idiopathic mesenteric AVM.CASE SUMMARY A 50-year-old male was admitted to our hospital due to abdominal pain that had persisted for 3 mo and bloody diarrhea.He had no history of trauma or abdominal surgery.He had undergone two colonoscopies 6 mo and 2 years ago,and they showed only a polyp.He was diagnosed with ischemic colitis with inferior mesenteric AVM following contrast-enhanced abdominal computed tomography(CT)and underwent rectal low anterior resection.He has not had a recurrence of symptoms for 3 years.His history showed that he had undergone non-enhanced abdominal CT 2,5,and 8 years ago when he had attacks of urinary stones.Retrospectively,dilation of blood vessels around the rectosigmoid colon could have been detected 5 years ago,and these findings gradually became more evident.CONCLUSION This is the first report of the natural history of inferior mesenteric AVM.

A low-grade cerebral arteriovenous malformation suspected of being a metastatic tumor:A case report and literature review

Cases of low-grade cerebral arteriovenous malformations(c AVMs)showing dynamic changes and large areas of brain edema on short-term MRI follow-up have rarely been reported.This report describes an incidentally discovered and initially misdiagnosed c AVM in a patient with malignancies.The presence of abnormal signals surrounded by large areas of brain edema combined with tortuous or dilated vessels indicates the possibility of an AVM,especially in young people.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room

Objective Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years.However,reports on one-session hybrid surgery for arteriovenous malformations(AVMs)are relatively rare.The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room(OR)at one stage.Methods We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018.The data for resection rate,microcatheter adhesion,surgical position and postoperative outcomes were analyzed.Total resection or near-total resection was achieved in all cases.Results A total of 13 patients were under combined endovascular and surgical procedures,and 7 experienced surgery with intraoperative digital subtraction angiography.Sitting position was applied in 3 of them;2 niduses in cerebellum,and 1 in parietal lobe.Compared with admission modified Rankin Scale(mRS)in all patients,postoperative 12-month mRS showed a significant decline.Besides,3 patients experienced microcatheter adhesion after endovascular embolization,thereafter underwent surgical adhesion removal while nidus resection was done.Conclusion Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs.The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position.It also reduces the risk of microcatheter adhesion,which enables interventional radiologists to perform aggressively.

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Expression of angiogenic factors in cerebral arteriovenous malformations

BACKGROUND： In the process of vascularization, vascular endothelial growth factor （VEGF）, angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE： To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN： An observational comparative experiment. SETTINGS： Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS： Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS： ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen（PCNA） in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens （specific marker of vascular endothelial cells） were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in ＂mirror＂ relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative （ - ）： no positive cells; positive （＋）： number of positive cells 〈 20%; moderately positive （＋＋）： number of positive cells 20% - 50%; strongly positive （＋＋＋）： number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES： Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS： ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade： The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade （ x^2=21.09 - 34.23, P 〈 0.05）, whereas the positive rates of Tiel and angiopoietin-1 expressions were close （ x^2=3.43 - 3.869, P 〉 0.05）. ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group： The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group （ x^2= 16.22 - 26.56, P 〈 0.05）. There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group （ x^2=3.22 - 3.78, P 〉 0.05）.The VEGF was positively correlated with the expressions of c-myc and PCNA （r = 0.728, 0.916, P 〈 0.05）. CONCLUSION： ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.

Treatment for arteriovenous malformation of the brain Comparison between microsurgery and gamma knife

Microsurgery and gamma knife are the mainly ways to treat arteriovenous malformation of brain in grade Spetzler-Martin I -III; however, therapeutic effects of them need to be further studied. OBJECTIVE： To compare the therapeutic effects between microsurgery and gamma knife on the treatment of arteriovenous malformation of brainin grade Spetzler-Martin I-III. DESIGN： Retrospective analysis. SETTING： Department of Neurosurgery, the Third Hospital Affiliated to Sun Yat-sen University; Guangdong Microinvasion Center. PARTICIPANTS： A total of 86 patients with arteriovenous malformation of the brain were selected from the Department of Neurosurgery, the Third Hospital Affiliated to Sun Yat-sen University and Guangdong Microinvasion Center from January 1997 to February 2007. After DSA, CT and/or MRI examinations, patients were evaluated in grade Spetzler-Martin I -III. All patients were divided into microsurgery group （n = 34） and gamma knife group （n =52）. There were 22 males and 12 females in the microsurgery group and their mean age was 26 years, while there were 34 males and 18 females in the gamma knife group and their mean age was 28 years. The grade of Spetzler-Martin was comparable in the two groups. All their relatives provided the confirmed consent and the study was allowed by ethics committee of our hospital. METHODS： Under complete anesthesia, patients were given microsurgery and the operative approach was chosen based on diseased regions. Firstly, feeding artery was blocked; secondly, it was separated along band of gliosis between malformation vessel mass and brain tissue; finally, draining vein was cut off and malformation vessel mass was resected. On the other hand, patients in the gamma knife group received Leksell-2300B gamma knife treatment. Leksell-G stereotaxis headframe was installed; GEl .STMR scanning device was used for localization; r-PlanS.2 workstation was used for target design and dosage program; Leksell B gamma knife was used during the whole operative procedure. The target was l - 4 and peripheral dosage was 12- 28 Gy. At 0.5, l and 2 years after operation, angiography was used to detect vascular occlusion in the two groups. Meanwhile, focal hemorrhage and new neurological function defect （including hemiplegic paralysis, language disorder, cerebellar function disorder, increasing frequency of epilepsy, etc.） were also observed. MAIN OUTCOME MEASURES： Rate of vascular occlusion, focal hemorrhage and neurological function defect at different time points after operation. RESULTS： All 86 patients were involved in the final analysis. Vascular nest of patients in the microsurgery group disappeared completely; while, two patients （6%, 2/34） had new neurological function defect but did not have rehaemorrhagia and death after operation. On the other hand, vascular nest of 43 patients （83%, 43/52） in the gamma knife group disappeared completely, and 8 （l 5%, 8/52） had new neurological function defect. There was significant difference between the two groups （ x^2=2.63, P 〈 0.05）. Six patients （12%, 6/52） in the gamma knife group had rehaemorrhagia after operation, and one （2%, 1/52） died. CONCLUSION： Both microsurgery and gamma knife have great effects on the treatment of arteriovenous malformation of brain in grade Spetzler-Martin I-III;however, the therapeutic effects ofmicrosurgery are superior to those of gamma knife.

Surgical strategy for cerebral arteriovenous malformation with acute hemorrhage

BACKGROUND： Presently, there have been craniocerebral operation, interventional embolization,stereotactic radiotherapy and other methods in treating cerebral arteriovenous malformation （AVM）.However, the standard of different therapeutic regimens of cerebral AVM at the acute stage of hemorrhage has not been completely identified.OBJECTIVE： To observe the clinical characteristics and therapeutic effects of AVM at the acute stage of hemorrhage in patients, and to analyze corresponding therapeutic strategies.DESIGN： Non-randomized clinical observation.SETTING： Department of Neurosurgery, Foshan First People＇s Hospital, Sun Yat-sen University.PARTICIPANTS： Forty-six patients with cerebral AVM complicated by hemorrhage admitted to Department of Neurosurgery, Foshan First People＇s Hospital between January 1999 and December 2006,were involved in this study. All the patients were confirmed as cerebral AVM complicated by hemorrhage by brain angiography or/and postoperational pathology. The involved patients, 32 males and 14 females,averaged 25 years old, ranging from 6 to 62 years. Informed consents of therapeutic items were obtained from the relatives of all the patients.METHODS： ①On admission, skull CT and brain angiography were conducted in the involved subjects. ②The therapeutic method was confirmed according to the consciousness, hematoma region, hematoma volume,imageological results following comprehensive analysis： DSA examination was permitted to identify the size and position of abnormal vessel mass, and the distribution of feeding artery and draining vein. Craniocerebral operation was carried out as early as possible in patients with severe or progressive conscious disturbance, in which most of hematoma with obvious occupied effect or cerebral hernia was located in lobe of brain. The primary thing was to clean intracerebral hematoma for in time decompression. According to different situations, corresponding therapeutic measures were used for resecting abnormal vessel mass, and the treatments of patients were observed. ③The therapeutic effects were assessed following Glasgow outcome scale（GOS） at 3 months after hemorrhage.MAIN OUTCOME MEASURES： ①The examination results of skull CT and brain angiography of patients on admission. ②Treatment of patients. ③GOS results at 3 months after hemorrhage.RESULTS： Forty-six patients were involved, and all of them participated in the final analysis. ① Examination results of skull CT and brain angiography： Bleeding part： frontal lobe in 7 cases, parietal lobe 15, temporal lobe 19, occipital lobe 3, cerebellar hemisphere 2, and hemorrhage rupturing into ventricle 10. Haematoma volume： small volume of hematoma （〈20 mL） in 4 cases, moderate volume of hematoma （20 - 50 mL） 14, large volume of hematoma （ 50 - 80 mL） 21, great volume of hematoma （〉80 mL） 7; Abnormal vessel mass： Among 17 patients undergoing aortocranial angiography, abnormal vessel mass was found in 16 patients, including cortex 13 patients, basal ganglia and thalamencephalon（deep part） 2 patients, and posterior cranial fossa 1 patient. The size of abnormal vessel mass： small （〈3 cm） 4 patients, moderate （3 -6 cm） 9 patients, and large （〉6 cm） 3 patients. The type of feeding artery： perforating branch blood-supply 1 patient, cortical branch blood supply 13 patients, mixed branch blood supply 2 patients. The type of draining vein： cortical draining （superficial part） 10 patients, deep part draining 2 patients, and mixed draining 4 patients. ② Treatment condition： Among 17 patients undergoing brain angiography followed by craniocerebral operation, hematoma was removed and AVM was completely resected in 12 patients, hematoma was removed and AVM was partially resected in 3 patients, and only hematoma was resected in 2 patients; Among 24 patients undergoing emergent craniocerebral operation, hematoma was removed and AVM was completely resected in 5 patients, hematoma was removed and AVM was partially resected in 9 patients, and only hematoma was resected in 10 patients; Expectant treatment was carried out in the early stage in 5 patients. When disease condition was stable, AVM resection was separately or complicatedly conducted in 13 patients, embolization in 4 patients, and γ - radiotherapy in 5 patients. ③GOS： 5 patients died in postoperative complications, and among the other patients, 19 had moderate or had not functional impairment, 13 had moderate disability, 6 had severe disability, 2 were vegetative state, and 2 died. ④Post-operative re-examination of brain angiography： Among 16 patients undergoing AVM, vessel mass disappeared in 9 patients.CONCLUSION： Good therapeutic effects can be obtained by choosing proper therapeutic regimen according to clinical and imageological characteristics of patients with arteriovenous malformation complicated by hemorrhage at the acute stage.

Understanding the role of miRNAs in the pathogenesis of brain arteriovenous malformations

Brain arteriovenous malformations(AVMs)are abnormal vessels that are prone to rupture,ausing life threatening intracerebral hemorrhage(ICH).Understanding the moleaular basis of pathogenesis,timely diagnosis,and treatment of brain AVMs are some of the urgent problems in neur osur gery.MiaoRNAs(miRNAs)are small endogenous RNAs that regulate gene-epression psttranscriptionally.MiRNAs are involved in almost all biological procsss,induding cell proliferation,apoptosis,and cell differentiation.Recent studies have shown that miRNAs an be involved in brain AVMs formation and rupture.There are also extracellular forms of miRNAs.Circulating miRNAs have been detected in the blood circulation and other body fluids.Owing to their stability and resistance to endogenous RNase activity,circulating miRNAs have been proposed as diagnostic and prognostic biomarkers for various diseases,such as tumors,cardiovascular and autoimmune diseases.In this review,we summarized the role of some miRNAs in brain AVMs pathogenesis and discussed their potential cdinical appliation as non-invasive biomarkers.

De novo brain arteriovenous malformation formation and development:A case report

BACKGROUND Brain arteriovenous malformation(AVM),an aberrant vascular development during the intrauterine period,is traditionally considered a congenital disease.Sporadic reports of cases of de novo AVM formation in children and adults have challenged the traditional view of its congenital origin.CASE SUMMARY In this report,we have presented the case of a child with a de novo brain AVM.Magnetic resonance imaging and magnetic resonance angiography of the brain showed no AVM at the age of 5 years and 2 mo.Brain AVM was first detected in this child at the age of 7 years and 4 mo.The brain AVM was significantly advanced,and hemorrhage was seen for the first time at the age of 12 years and 8 mo.There was further progression in the AVM,and hemorrhage occurred again at the age of 13 years and 5 mo.Genetic analysis of this patient revealed a mutation in the NOTCH2(p.Asp473 Val)gene.CONCLUSION In short,our case has once again confirmed the view that brain AVM is an acquired disease and is the result of the interaction of genes,environment,and molecules.

Management of Ruptured Scalp Arteriovenous Malformation: A Rare Case and Literature Review

Arteriovenous malformation (AVM) are vascular anomalies that arise due to abnormal connection with shunting of blood from arteries to veins without an intervening capillary network. They are mostly found intracranially but extracranially, the scalp AVM cases are also well reported. However, arteriovenous malformation (AVM) of the scalp is a rare lesion whose natural history is not clearly understood. The clinical manifestation of AVM includes asymptomatic state, local discomfort, headaches and occasional scalp necrosis leading to massive haemorrhage. CT or MR angiography remains the cornerstone for investigation. The options of treatment include complete surgical excision, embolization or a combination of the two modalities. We present the successful management of a young man who presented with a torrential bleeding from a ruptured scalp arteriovenous malformation and had to undergo emergency complete excision followed with a rotational flap for the scalp reconstruction.

A Patient with Spinal Arteriovenous Malformation Treated with Lumbar Vertebral Surgery Due to Misdiagnosis

Spinal arteriovenous malformation (AVM) is a rare disease that arises more commonly from the lower thoracic and upper lumbar spine. It is classified based on the development pattern and the shunt location. The developmental mechanism of the symptoms is thought to be as follows. Spinal venous return is impaired by high-pressure arterial blood flowing into the coronary sinus via a shunt and venous pressure is promoted, which causes spinal cord symptoms to progress gradually. Listlessness, pain, and an abnormal sensation of the lower limb are possible initial symptoms. Spinal AVM may cause intermittent claudication and bladder and rectal disturbance, and differentiation from lumbar degenerative diseases and arteriosclerosis obliterans is required, which may cause difficulty with diagnosis. We encountered a patient in whom intermittent claudication was treated with lumbar decompression and fixation at another hospital, but symptoms did not improve. The patient was diagnosed with spinal AVM at our hospital and symptoms were improved by surgery. Because the symptoms did not improve despite being treated with surgery for spinal canal stenosis, we strongly suspected spinal intermittent claudication, and we performed a spinal CT and MRI after myelography for the entire spinal cord, and identified the lesion in the thoracic spinal cord. Regarding the postoperative outcome and prognosis of spinal dural AVF, early diagnosis and early treatment have been proposed as prognostic factors because the postoperative outcome is poor in patients with high preoperative severity and a long duration of illness. In our patient, the preoperative JOA score was 6, showing high preoperative severity, and the duration of illness was 1.5 years before diagnosis, which may explain the limited improvement of the JOA score to 20 at final follow-up. In a case with these characteristics, we suggest that close examination of the entire spinal cord is needed for effective treatment.

Bleomycin inhibits CLEC14A to attenuate the progression of extracranial arteriovenous malformations

Background:We previously reported that interstitial injection of bleomycin(BLM)reduces the size of early-stage extracranial arteriovenous malformation(AVM).Here,we sought to investigate the potential mechanism of BLM in treating extracranial AVM.Methods:Samples of human extracranial AVM(n=3)with no pharmacological treatment were harvested.AVM endothelial cells were isolated and cultured in primary cell culture.The transcriptome was examined using RNAsequencing,and differentially expressed C-type lectin domain family 14 member A(CLEC14A)was validated at the transcriptomic and protein levels.Immunocytochemical staining of CLEC14A was performed in samples of human extracranial AVM,with and without BLM treatment.Results:Through second-generation sequencing,we found that the expression of 5689 genes were differentially increased or decreased following 24-h BLM stimulation.We found that CLEC14A may play an important role in the progression of AVM and can be inhibited by BLM treatment.Conclusion:BLM inhibited CLEC14A expression to attenuate the progression of AVM.