scholarly journals Gene Mutations Related to Pathogenesis and Development of Cerebral Arteriovenous Malformations in Pediatric Populations

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Rebecca Y Du ◽  
Melissa LoPresti ◽  
Vijay Ravindra ◽  
Ionela Iacobas ◽  
Katie Bergstrom ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Arteriovenous Malformations ◽  
Gene Mutations ◽  
Pediatric Neurosurgery ◽  
Vascular Anomalies ◽  
Genetic Mutations ◽  
Cerebral Arteriovenous Malformations ◽  
Cavernous Malformations ◽  
Pik3ca Mutations

Abstract INTRODUCTION Cerebral arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients. Recurrence after complete surgical resection is a recognized risk that occurs primarily in children. While Pediatric Neurosurgery practices traditionally focus on clinical management, recent advances have found gene mutations to play a role in pathogenesis and development of AVMs It is not known how many pediatric AVMs are sporadic versus arising from familial inheritance patterns. We aimed to see how identified genetic mutations are represented in our AVM patient population in Texas and the southern United States. METHODS We developed a multidiscipinary pediatric neurovascular program at our institution. Patients and families were screened in their first-time and/or follow-up outpatient clinic encounters by our hematologist-oncologist and genetics counsellor from the Pediatric Vascular Anomalies program. Genetic testing recommendations and results were recorded in our IRB-approved ongoing prospective neurovascular database. RESULTS 50 patients were screened in Vascular Anomalies program. Diagnoses ranged from AVMs (n = 20), cerebral cavernous malformations (n = 13), non-NF/non-sickle-cell moyamoya (n = 7), and other lesions such as cerebral proliferative angiopathy and megelencephaly-capillary malformation. Of the 50 patients, 30 underwent genetic testing. 7 had identified mutations. 3 patients with cavernous angiomas had Krit1 mutations. 2 patients with AVMs had Rasa1 mutations, and 2 patients with megenecephaly-capillary malformations had PIK3CA mutations. CONCLUSION These preliminary findings highlight the importance of thinking beyond neurosurgical intervention for pediatric neurovascular diseases. Genetic mutations have been found in 23% of patients screened thus far. Such findings provide insight into disease biology and may likely have clinical implications for risk assessment, family screening, and follow-up surveillance. Further work needs to be done to capture all our AVM population for genetic screening over time, while expanding our neurovascular program's study focus to encompass all neurovascular pathologies.

scholarly journals P03.08 Large cerebral arteriovenous malformations management with Volume-staged gamma knife radiosurgery

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii26-iii26
Author(s):  
R M Emad Eldin ◽  
W A Reda ◽  
A M El-Shehaby ◽  
K Abdel Karim ◽  
A Nabeel ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Gamma Knife Radiosurgery ◽  
Cerebral Arteriovenous Malformations ◽  
Factors Affecting ◽  
Prescription Dose ◽  
The Mean ◽  
Cerebral Avms ◽  
Grade 3

Abstract BACKGROUND Large cerebral arteriovenous malformations (AVM) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged gamma knife radiosurgery (VSGR) has been developed for the treatment of large AVMs, to increase the efficacy and improve safety of treatment of these lesions. The aim of the study was to assess the efficacy and safety of VSGR technique for the treatment of large cerebral AVMs. METHODS The study included patients treated by VSGR between May 2009 and July 2015. All cases had large AVMs (>10 cc). These were 29 patients. RESULTS Twenty-four patients completed radiographic follow up with 15 obliteration cases (62.5%). There was a total of 56 sessions performed. The mean AVM volume was 16 cc (10.1–29.3 cc). The mean prescription dose was 18 Gy (14–22 Gy). The mean follow up duration was 43 months (21–73 months). One patient died during follow up from unrelated cause. Two cases suffered haemorrhage during follow up. Symptomatic edema developed in 5 (17%) patients. The factors affecting obliteration were smaller total volume, higher dose/stage, non-deep location, compact AVM, AVM score less than 3, >18 Gy dose and <15 cc total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (p 0.012). T2 image changes were affected by SM grade 3 or more (p 0.013) and AVM score 3 or more (p 0.014). CONCLUSION VSGR provides an effective and safe treatment option for large cerebral AVMs. Smaller AVM volume is associated with higher obliteration rate.

scholarly journals Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases

2017 ◽  
Vol 126 (4) ◽  
pp. 1056-1063 ◽  
Author(s):  
Johannes Schramm ◽  
Karl Schaller ◽  
Jonas Esche ◽  
Azize Boström
Keyword(s):  
Arteriovenous Malformations ◽  
Consecutive Series ◽  
Cerebral Arteriovenous Malformations ◽  
Class A ◽  
Significant Deficit ◽  
Microsurgical Resection ◽  
Martin Grade ◽  
Grade Iii

OBJECTIVE The objective of this study was to review the outcomes after microsurgical resection of cerebral arteriovenous malformations (AVMs) from a consecutive single-surgeon series. Clinical and imaging data were analyzed to address the following questions concerning AVM treatment in the post-ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) era. 1) Are the patients who present with unruptured or ruptured AVMs doing better at long-term follow-up? 2) Is the differentiation between Ponce Class A (Spetzler-Martin Grade I and II) patients versus Ponce Class B and C patients (Spetzler-Martin Grade III and IV) meaningful and applicable to surgical practice? 3) How did the ARUBA-eligible patients of this surgical series compare with the results reported in ARUBA? METHODS Two hundred eighty-eight patients with cerebral AVMs underwent microsurgical resection between 1983 and 2012 performed by the same surgeon (J.S.). This is a prospective case collection study that represents a consecutive series. The results are based on prospectively collected, early-outcome data that were supplemented by retrospectively collected, follow-up data for 94% of those cases. The analyzed data included the initial presentation, Spetzler-Martin grade, obliteration rates, surgical and neurological complications, and frequency of pretreatment with embolization or radiosurgery. The total cohort was compared using “small-AVM,” Spetzler-Martin Grade I and II, and ARUBA-eligible AVM subgroups. RESULTS The initial presentation was hemorrhage in 50.0% and seizures in 43.1% of patients. The series included 53 Spetzler-Martin Grade I (18.4%), 114 Spetzler-Martin Grade II (39.6%), 90 Spetzler-Martin Grade III (31.3%), 28 Spetzler-Martin Grade IV (9.7%), and 3 Spetzler-Martin Grade V (1.0%) AVMs. There were 144 unruptured and 104 ARUBA-eligible cases. Preembolization was used in 39 cases (13.5%). The occlusion rates for the total series and small AVM subgroup were 99% and 98.7%, respectively. The mean follow-up duration was 64 months. Early neurological deterioration was seen in 39.2% of patients, of which 12.2% had permanent and 5.6% had permanent significant deficits, and the mortality rate was 1.7% (n = 5). Outcome was better for patients with AVMs smaller than 3 cm (permanent deficit in 7.8% and permanent significant deficit in 3.2% of patients) and Ponce Class A status (permanent deficit in 7.8% and significant deficit in 3.2% of patients). Unruptured AVMs showed slightly higher new deficit rates (but 0 instances of mortality) among all cases, and in the small AVM and Ponce Class A subgroups. Unruptured Spetzler-Martin Grade I and II lesions had the best outcome (1.8% permanent significant deficit), and ARUBA-eligible Spetzler-Martin Grade I and II lesions had a slightly higher rate of permanent significant deficits (3.2%). CONCLUSIONS Microsurgery has a very high cure rate. Focusing microsurgical AVM resection on unruptured lesions smaller than 3 cm or on Spetzler-Martin Grade I and II lesions is a good strategy for minimizing long-term morbidity. Well-selected microsurgical cases lead to better outcomes than with multimodal interventions, as in the ARUBA treatment arm, or conservative treatment alone. Long-term prospective data collection is valuable.

scholarly journals Gamma Knife surgery for incidental cerebral arteriovenous malformations

2014 ◽  
Vol 121 (5) ◽  
pp. 1015-1021 ◽  
Author(s):  
Chun-Po Yen ◽  
Dale Ding ◽  
Ching-Hsiao Cheng ◽  
Robert M. Starke ◽  
Mark Shaffrey ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Latency Period ◽  
Invasive Procedure ◽  
Gamma Knife Surgery ◽  
Neurological Deficits ◽  
Cerebral Arteriovenous Malformations ◽  
Long Term Follow Up

Object A relatively benign natural course of unruptured cerebral arteriovenous malformations (AVMs) has recently been recognized, and the decision to treat incidentally found AVMs has been questioned. This study aims to evaluate the long-term imaging and clinical outcomes of patients with asymptomatic, incidentally discovered AVMs treated with Gamma Knife surgery (GKS). Methods Thirty-one patients, each with an incidentally diagnosed AVM, underwent GKS between 1989 and 2009. The nidus volumes ranged from 0.3 to 11.1 cm3 (median 3.2 cm3). A margin dose between 15 and 26 Gy (median 20 Gy) was used to treat the AVMs. Four patients underwent repeat GKS for still-patent AVM residuals after the initial GKS procedure. Clinical follow-up ranged from 24 to 196 months, with a mean of 78 months (median 51 months) after the initial GKS. Results Following GKS, 19 patients (61.3%) had a total AVM obliteration on angiography. In 7 patients (22.6%), no flow voids were observed on MRI but angiographic confirmation was not available. In 5 patients (16.1%), the AVMs remained patent. A small nidus volume was significantly associated with increased AVM obliteration rate. Thirteen patients (41.9%) developed radiation-induced imaging changes: 11 were asymptomatic (35.5%), 1 had only headache (3.2%), and 1 developed seizure and neurological deficits (3.2%). Two patients each had 1 hemorrhage during the latency period (116.5 risk years), yielding an annual hemorrhage rate of 1.7% before AVM obliteration. Conclusions The decision to treat asymptomatic AVMs, and if so, which treatment approach to use, remain the subject of debate. GKS as a minimally invasive procedure appears to achieve a reasonable outcome with low procedure-related morbidity. In those patients with incidental AVMs, the benefits as well as the risks of radiosurgical intervention will only be fully defined with long-term follow-up.

scholarly journals Curative Glubran 2 Embolization of Cerebral Arteriovenous Malformations Patient Selection and Initial Results

2014 ◽  
Vol 20 (6) ◽  
pp. 722-728 ◽  
Author(s):  
Jie Liu ◽  
Ming Lv ◽  
Xianli Lv ◽  
Hongwei He ◽  
Aihua Liu ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Arteriovenous Malformations ◽  
Gamma Knife Radiosurgery ◽  
Clinical Results ◽  
Hemorrhagic Complication ◽  
Cerebral Arteriovenous Malformations ◽  
Complete Obliteration ◽  
Glubran 2 ◽  
Cerebral Avms

The liquid embolic agents currently used for embolization of cerebral arteriovenous malformations are Onyx and NBCA. Glubran 2, a cyanoacrylate-based synthetic glue, has recently been applied for embolization of cerebral arteriovenous malformations (AVMs). We report the clinical results of selected cerebral AVMs treated with Glubran 2 targeting for curative embolization. Between October 2011 and March 2013, 31 patients with cerebral AVMs were selected for curative embolization with Glubran 2. There were 19 men and 12 women with a mean age of 32 years (range 4–65 years). Initial clinical presentation included hemorrhage in 28 and seizures in three patients. AVM location was frontal in eight patients, parietal in four, occipital in eight temporal in six, cerebellar in two and cerebellar vermis in three patients. Follow-up was performed clinically and with angiography examination at three to six months. Clinical outcomes were evaluated based on the modified Rankin Scale (mRS). A mean of 2.5 (range, 1–12) feeding pedicles were embolized per patient. Complete angiographic obliteration of AVM was achieved in 27 patients. A hemorrhagic complication was observed in one patient, an ischemic complication in one patient and technical complications in four patients. There was no procedure-related disabling neurological deficit or death at discharge. Additional gamma knife radiosurgery was performed in five patients, including one patient with recurrent AVM. All of the patients had favorable clinical outcomes at three to six month follow-up (mRS≤2). The curative embolization technique with Glubran 2 for selected cerebral AVMs achieved a high initial complete obliteration rate with an acceptable complication frequency.

scholarly journals Endovascular Therapy Followed by Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

2006 ◽  
Vol 12 (1_suppl) ◽  
pp. 163-166 ◽  
Author(s):  
Y. Arai ◽  
Y. Handa ◽  
H. Ishii ◽  
Y. Ueda ◽  
H. Uno ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Arteriovenous Malformations ◽  
High Rate ◽  
Neurological Deficits ◽  
Cerebral Arteriovenous Malformations ◽  
Increased Risk ◽  
Irradiation Therapy ◽  
Complete Obliteration ◽  
Vascular Structures

Pre-radiosurgical embolization was carried out using cyanoacrylate in seven of 13 patients with cerebral arteriovenous malformations (AVMs) treated by stereotactic radiosurgery (SRS) with a linear accelerator (LINAC). The aim of embolization before SRS was the reduction of AVM volume and/or the elimination of vascular structures bearing an increased risk of haemorrhage. Staged-volume SRS was also performed in two patients because of residual irregular shaped nidus of AVMs even after the embolizations. Complete obliteration of the AVM nidus on angiogram was presented in five patients with embolizations (including one with staged-volume SRS) and in three of six patients with SRS alone, during follow-up periods after radiosurgery. No patients experienced haemorrhagic events after SRS. Although transient neurological symptoms were observed after embolizations in two patients, no permanent neurological deficits were presented in all patients with SRS. Pre-radiosurgical embolization may allow the effective influence on irradiation therapy in relatively large AVMs and promote more frequent obliteration in more small sized AVMs compared to those with SRS alone. However, further study must be needed to determine whether staged-volume SRS provides a high rate of AVM obliteration and its safeness.

scholarly journals Adenosine-induced Cardiac Standstill to Facilitate Endovascular Embolisation of Cerebral Arteriovenous Malformations in Children

2009 ◽  
Vol 37 (4) ◽  
pp. 619-623 ◽  
Author(s):  
G. D. Puri ◽  
I. Sen ◽  
J. R. Bapuraj
Keyword(s):  
General Anaesthesia ◽  
Arteriovenous Malformations ◽  
High Flow ◽  
Cerebral Arteriovenous Malformations ◽  
Neurological Outcomes ◽  
Endovascular Embolisation ◽  
Glue Injection ◽  
Controlled Deposition ◽  
One Year

This report describes three children, aged eight to 11 years, with high-flow cerebral arteriovenous malformations who underwent interventional neuroradiological procedures involving glue (N-butyl cyanoacrylate) embolisation under general anaesthesia. The procedure was facilitated by relative hypotension induced by esmolol infusion and intravenous adenosine boluses. To allow controlled deposition of N-butyl cyanoacrylate into the arteriovenous malformations, glue injection was synchronised with the onset of adenosine-induced brief cardiac standstill. This resulted in satisfactory obliteration of the arteriovenous malformations nidus in all cases. The haemodynamic modulations, including the adenosine-induced brief cardiac standstill, was noted to not affect the BIS values in our patients. All patients had satisfactory obliteration of their arteriovenous malformations and had good neurological outcomes at one-year follow-up.

scholarly journals Disfiguring high-flow cervicofacial arteriovenous malformations

2020 ◽  
Vol 2020 (10) ◽  
Author(s):  
Alaa Nabawi ◽  
Nader Abraham ◽  
Ayman Nabawi
Keyword(s):  
Oral Cavity ◽  
Vascular Malformation ◽  
Arteriovenous Malformations ◽  
Case Series ◽  
High Flow ◽  
Vascular Anomalies ◽  
Maxillofacial Region ◽  
Clinical Onset ◽  
Life Threatening

Abstract Arteriovenous malformations (AVMs) are congenital vascular anomalies resulting from defects in angiogenesis. Approximately 40% of AVMs go undetected after birth and only experience the delayed clinical onset of symptoms in adulthood. AVMs are rare, representing only 1.5% of all vascular anomalies. The most common sites for the aberrant vascular nidus are the oral cavity and maxillofacial region, which represent 50% of the cases. AVMs are the most challenging and life-threatening form of vascular malformation. Exsanguination, thrombus detachment and embolization are the most hazardous operative risks. Small case series revealed a 75% recurrence rate during a 5-year follow-up, which adds another layer of complexity to their management. Large lesions in the head and neck cause deformation to the patient and present a challenge to the surgeon during their excision among vital structures and reconstruction of the 3D complex defects.

Consistency evaluation of lung adenocarcinoma tissue and circulating tumor cells related gene mutation detection based on multi-site immunomagnetic beads

2022 ◽  
pp. 088532822110658
Author(s):  
Keying Xue ◽  
Bingqing Luo ◽  
Xiaoqing Li ◽  
Weixian Deng ◽  
Chunyan Zeng ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Targeted Therapies ◽  
Sanger Sequencing ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Separation System ◽  
Tumor Tissues

This study was designed to investigate the feasibility of genetic testing using circulating tumor cells (CTCs) instead of tumor tissues in lung adenocarcinoma to break through its limitation. Separation system for epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), and Vimentin expressing CTCs was constructed and used to capture CTCs in the blood samples of 57 patients with lung adenocarcinoma. Genetic mutations of genes involved in targeted therapies were detected by next-generation sequencing (NGS) in tissues from these patients. Blood CTC samples with the gene mutations identified by tissue-NGS were selected and corresponding gene mutations were detected by Sanger sequencing. The specificity of the CTC separation system was 95.48% and the sensitivity was 90.85%. The average number of CTCs in the blood of patients with lung adenocarcinoma was 12.47/7.5 mL. Comparison of the tissue-NGS with the CTC-Sanger sequencing showed that the consistencies of genetic mutations of EGFR ( n = 24), KRAS ( n = 9), TP53 ( n = 19), BRAF ( n = 1), ERBB2 ( n = 2), and PIK3CA ( n = 3) were 92.31%, 75.00%, 86.36%, 50.00%, 66.67%, and 75.00%, with an overall consistency of 84.06%. The CTC separation system established in this study shows high specificity and sensitivity. CTCs can be used as a suitable alternative to tumor tissues that are difficult to obtain in clinical practice and overcome the difficulties in tumor tissue collection, which is of significance in guiding clinical medication and individualized treatment with significant clinical application value in terms of genetic testing for targeted therapies in tumor treatment.

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