Surgery Of Cerebral Arteriovenous Malformations Research Articles

160 Gamme Knife Radio Surgery for Cerebral Arteriovenous Malformation (AVM) in Children: A Systematic Review and Meta-analysis of Clinical Outcomes

INTRODUCTION: As radiosurgical devices are becoming more commonly used and applied to treat cerebral arteriovenous malformations (cAVMs), there is a growing concern about whether the outcomes of radiosurgery might differ between children, adolescents, and adults due to the distinct characteristics of cAVMs in these age groups. METHODS: Search: A search for RCT, not RCT, prospective and retrospective cohort studies in PUBMED; SCOPUS; Central Cochrane Registry ofControlled Trials (The Cochrane Library); MEDLINE; EMBASE (Ovid); CINAHL. The search strategy include subject headings (MeSH) and text words connected with Booleans term. Population: Children (younger than 18 years old) with Cerebral Arterio-venous Malformation (AVMs). Intervention: Gamma Knife radiosurgery (GKS). Outcomes: Primary Outcome: Mortality to end of Follow-up and Surgery successfull determined by the percentage of obliterated AVMs. Secondary Outcome: New Neurological deterioration and Post-Radiosurgery intracranial hemorrhage. RESULTS: 21 studies with 2142 children who had Gamma knife surgery for cerebral arteriovenous malformations were found for this systematic review. For children with cerebral AVMs treat with GKS, the death rate was 0.725% (95% CI 0.411%-1.126%; I2 = 0%) while the success rate of gamma knife radiosurgery was 71.74% (95% CI 65.716%-77.211%; I2 = 88.13). The rate of complications, such as the rate of new neurological deficits, was 2.57% (1.43% to 3.89%; I2 = 66.78%), and the postoperative intracranial bleeding rate was 2.463% (1.348% to 3.9%; I2 = 70.14%). CONCLUSIONS: Gamma Knife radiosurgery is a safe and effective treatment option for cerebral arteriovenous malformations, with high surgical success rates, low mortality, and low complication rates. However, further high-quality case-control studies are needed to evaluate its long-term efficacy and safety.

Non-Angry Superficial Draining Veins: A New Technique in Identifying the Extent of Nidus Excision during Cerebral Arteriovenous Malformation Surgery

As essential techniques, intraoperative indocyanine green video angiography (ICG-VA) and FLOW 800 have been widely used in microsurgery for arteriovenous malformations (AVMs). In the present report, we introduced a supplementary technical trick for judging the degree of lesion resection when there were superficial drainage veins. FLOW 800 analysis is used to verify our conjecture. A retrospective analysis of a 33 case cohort treated surgically from June 2020 to September 2022 was conducted and their lesions were removed by superficial drainage veins as a supplementary technical trick and analyzed with FLOW800. In our 33 AVMs, the feeding artery was visualized earlier than the draining vein. Intraoperatively, the T1/2 peak and slope of the draining vein were significantly higher than that of the lesion. However, the maximum fluorescence intensity (MFI) of the draining vein decreased as the procedure progressed (p < 0.001). After reducing the blood flow to the nidus by progressive dissection of the feeding artery, the arteriovenous transit time (AVTT) decreased from 0.64 ± 0.47 s, was prolonged to 2.38 ± 0.52 (p < 0.001), and the MFI and slope of the nidus decreased from the pre-resection 435.42 ± 43.90 AI and 139.77 ± 27.55 AI/s, and decreased to 386.70 ± 48.17 AI and 116.12 ± 17.46 AI/s (p < 0.001). After resection of the nidus, the T1/2 peak of the draining vein increased from 21.42 ± 4.70 s, prolonged to after dissection of the blood feeding artery, 23.07 ± 5.29 s (p = 0.424), and after resection of the lesion, 25.13 ± 5.46 s (p = 0.016), with a slope from 135.79 ± 28.17 AI/s increased to 210.86 ± 59.67 AI/s (p < 0.001). ICG-VA integrated with FLOW 800 is an available method for determining the velocity of superficial drainage veins. Whether the color of the superficial drainage veins on the cortical surface returns to normal can determine whether the lesion is completely resected and can reduce the possibility of residual postoperative lesions.

Evaluation of the Utility of Indocyanine Green Video Angiography in Cerebral Arteriovenous Malformation Surgery

To assess the utility of intraoperative indocyanine green video angiography (ICG-VA) during microsurgical resection of arteriovenous malformations (AVMs). Data of the 24 patients, who were surgically treated for AVM using intraoperative ICG-VA, were reviewed retrospectively. Postoperative digital subtraction angiography (DSA) was performed in all patients before they regained consciousness and became fully awake, and the results were compared with those obtained with intraoperative ICG-VA. A scheduled DSA was performed in all patients in the third, sixth, and twelfth postoperative months as well. Authors retrospectively analyzed the records of intraoperative ICG-VA application of all 24 patients. Though the exposures were limited and the image qualities were poor at higher magnification on the surgical microscope within deep surgical fields, the AVM niduses, feeding arteries, draining veins, and their relations to normal vasculature were observed precisely with ICG-VA in all the procedures. Furthermore, the visualization was not qualified enough to identify these pathological vascular structures accurately before evacuating and irrigating the layer of blood clots that obscure the view in patients who presented with hemorrhage. In a patient in our series, a residual nidus in the tail of the caudate nucleus was detected with immediate postoperative DSA which was not revealed by terminal assessment with final intraoperative ICG-VA. Intraoperative ICG-VA is particularly effective in the identification of the feeder, nidus, and drainer and in the assessment of the flow dynamics of the nidus in cerebral AVM surgery. It may be a quick and safe technique for intraoperative imaging of the angioarchitecture of superficial AVMs, but it may be less helpful for deep-seated lesions. Furthermore, this method alone may not be useful in the identification of residual disease or improvement of the clinical outcomes. DSA has remained the gold standard for confirming AVM obliteration. Despite the technical limitations associated with ICG-VA, a combination of intraoperative ICG-VA and immediate postoperative DSA may advance the safety and efficacy of AVM surgery.

Intractable brain swelling during cerebral arteriovenous malformation surgery due to contralateral acute subdural haematoma.

Severe brain swelling during routine neurosurgery can herald serious consequences. Failure to control brain swelling despite adequate measures warns of a surgical cause and should be dealt efficiently. We report a case of an adult female who developed intraoperative acute subdural haematoma (SDH) and consequent intractable brain swelling during surgery of supratentorial arteriovenous malformation (AVM). Such a manifestation of contralateral acute SDH during supratentorial AVM surgery has not been reported earlier.

Clinical Experience with Intraoperative Ultrasonographic Image in Microsurgical Resection of Cerebral Arteriovenous Malformations

Intraoperative ultrasonography is widely used in neurosurgery for the management of intracerebral hematoma and brain tumor. However, the clinical value of this method in the surgery of cerebral arteriovenous malformations (AVMs) has not been reported. In this study, the application of intraoperative ultrasonography for AVM surgery was evaluated prospectively. This prospective clinical study comprised 41 patients who underwent microsurgical resection of cerebral AVMs at our institute. After routine craniotomy, ultrasonographic imaging with color Doppler ultrasonography and real-time contrast-enhanced ultrasonographic angiography if necessary were applied as navigated images on the monitor during the operation. Ultrasonographic imaging made it easier to understand the vascular architecture during the operation. Color Doppler flow imaging clearly delineated the shape and margin of the AVMs. Intraoperative real-time contrast-enhanced ultrasonographic angiography enabled the surgeons to categorically identify AVM feeders both on the surface and deep in the tissue. Microneurosurgery with intraoperative ultrasonographic image guidance was a safe, effective, and reliable method for identifying the afferent and efferent vessels and for confirming the complete resection of AVMs. These benefits of image-guided microsurgery were mostly apparent for deep-seated AVMs that were not visible on the surface of the brain.

Delayed cyst formations and/or expanding hematomas developing after Gamma Knife surgery for cerebral arteriovenous malformations

The authors retrospectively analyzed cyst formations and expanding haematomas (EHs) that developed after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs), and evaluated the treatment results of these lesions. Cyst formations and/or EHs which developed after GKS for AVMs were identified in 20 patients (5.0%) out of 404 patients who underwent this procedure. There were nine patients with cyst formations, two with EHs and nine with cyst formations with EHs. These lesions developed between 36 and 192months (median 99months) after GKS. The median nidus volume was 4.7ml (range, 1.8–14.2ml) and the median prescribed margin dose was 20Gy (range, 15–23Gy). The multivariate analysis showed no correlation between the appearance of cyst formations and/or EHs and the patients’ age, sex, nidus volume, margin dose, repeated GKS, nidus obliteration, pre-GKS embolization and prior hemorrhage. Surgical treatment was required in nine patients. Eight patients had total removal of the angiomatous lesions (EHs or nodular lesions that were detected as enhancement part on MRI) via a craniotomy and one had a cyst aspiration. There was no recurrence of the lesions in all the patients that underwent a craniotomy. In the patient treated with a cyst aspiration, regrowth of the cyst formation occurred. Surgical treatment should be considered for symptomatic lesions and we recommend total removal of the angiomatous lesions to achieve a complete cure.

Does FLOW 800 Technology Improve the Utility of Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery?

Does FLOW 800 Technology Improve the Utility of Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery?

Erratum: Risks of history of diabetes mellitus, hypertension, and other factors related to radiation-induced changes following Gamma Knife surgery for cerebral arteriovenous malformations

Erratum: Risks of history of diabetes mellitus, hypertension, and other factors related to radiation-induced changes following Gamma Knife surgery for cerebral arteriovenous malformations

Risks of history of diabetes mellitus, hypertension, and other factors related to radiation-induced changes following Gamma Knife surgery for cerebral arteriovenous malformations

Diabetes mellitus (DM) and hypertension may be associated with complications following fractionated radiotherapy. To date no studies have determined the risk of radiation toxicity in patients with DM or hypertension who have undergone Gamma Knife surgery (GKS) for brain arteriovenous malformations (AVMs). The goal of the present study was to determine associations between DM or hypertension and other factors in the development of radiotoxicity, as measured by radiation-induced changes (RICs) on MR images following radiosurgery for AVM. Using univariate methods and multivariate logistic regression, the authors compared the RIC status in patients 18 years of age and older with these patients' history of, or medication use for, DM or hypertension; tobacco use; patient age and sex; AVM volume; Spetzler-Martin AVM severity scale (Grades I and II vs Grades III-V); AVM surgery, AVM embolization, or hemorrhage prior to radiosurgery; AVM location; number of draining veins; and radiosurgery margin dose. Radiation-induced changes occurred in 38% of 539 adults within a mean (± standard deviation) of 12 ± 10 months after radiosurgery, as observed during a median follow-up time of 55 months. Among patients in whom RICs occurred, 34% had headaches, neurological deficits, or new-onset seizures. Larger RICs were associated with worse symptoms. According to a univariate analysis, DM (3% of patients), larger AVM volume, worse Spetzler-Martin grade, lack of AVM surgery prior to radiosurgery, lack of hemorrhage prior to radiosurgery, and smaller margin dose of radiation had significant associations with the presence of RICs. Hypertension (20%), patient sex, tobacco use, number of draining veins, superficial or deep location of the lesion, and AVM embolization prior to radiosurgery had no association with the presence of RICs. According to a multivariate analysis, larger AVM volume, worse Spetzler-Martin grade, and no AVM surgery prior to radiosurgery predicted the occurrence of an RIC. Diabetes mellitus had borderline significance. Vascular factors such as hypertension, patient sex, and tobacco use did not convey additional risks of radiotoxicity, but DM remained a possible cardiovascular risk factor in the development of RICs.

Radiation-induced imaging changes following Gamma Knife surgery for cerebral arteriovenous malformations

The objective of this study was to evaluate the incidence, severity, clinical manifestations, and risk factors of radiation-induced imaging changes (RIICs) following Gamma Knife surgery (GKS) for cerebral arteriovenous malformations (AVMs). A total of 1426 GKS procedures performed for AVMs with imaging follow-up available were analyzed. Radiation-induced imaging changes were defined as newly developed increased T2 signal surrounding the treated AVM nidi. A grading system was developed to categorize the severity of RIICs. Grade I RIICs were mild imaging changes imposing no mass effect on the surrounding brain. Grade II RIICs were moderate changes causing effacement of the sulci or compression of the ventricles. Grade III RIICs were severe changes causing midline shift of the brain. Univariate and multivariate logistic regression analyses were applied to test factors potentially affecting the occurrence, severity, and associated symptoms of RIICs. A total of 482 nidi (33.8%) developed RIICs following GKS, with 281 classified as Grade I, 164 as Grade II, and 37 as Grade III. The median duration from GKS to the development of RIICs was 13 months (range 2-124 months). The imaging changes disappeared completely within 2-128 months (median 22 months) following the development of RIICs. The RIICs were symptomatic in 122 patients, yielding an overall incidence of symptomatic RIICs of 8.6%. Twenty-six patients (1.8%) with RIICs had permanent deficits. A negative history of prior surgery, no prior hemorrhage, large nidus, and a single draining vein were associated with a higher risk of RIICs. Radiation-induced imaging changes are the most common adverse effects following GKS. Fortunately, few of the RIICs are symptomatic and most of the symptoms are reversible. Patients with a relatively healthy brain and nidi that are large, or with a single draining vein, are more likely to develop RIICs.

Intra-arterial injection of indocyanine green in cerebral arteriovenous malformation surgery

Surgical microscope-integrated intraoperative angiography with intra-venous injection of indocyanine green (ICG) has been widely used during bypass or aneurysm surgery. Instead of intra-venous injection of ICG, we describe a case of intraoperative video angiography with intra-arterial injection of ICG in cerebral arteriovenous malformation (AVM) surgery. During the surgery, we injected ICG through a catheter placed in the internal carotid artery in each step. The technique was feasible and useful to distinguish feeders from normal arteries and to observe changes in flow dynamics. Intra-arterial injection of ICG had better phase contrast than intra-venous injection of ICG and better spatial resolution than digital subtraction angiography. Therefore, this technique can be helpful in cerebral AVM surgery.

Gamma Knife for Cerebral Arteriovenous Malformations at a Single Centre

We report the results of a consecutive series of patients treated with Gamma Knife (GK) Surgery for cerebral arteriovenous malformations (AVMs). We retrospectively reviewed 69 patients treated with GK for cerebral AVMs between November 2003 and April 2009, recording clinical data, treatment parameters, and AVM obliteration rates in order to assess our effectiveness with GK in treating these lesions. Ten patients were lost to follow-up. Presentations included: seizure (24), hemorrhage (18), persistent headache (12), progressing neurological signs (10), and incidental (9). In 24 patients (34.8%) treatment planning consisted of digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and computed tomogram (CT) angiography (CTA). Currently we rely predominantly on CTA and/or MRI scanning only. Fourty-one patients have been followed for a minimum of 3 years; average age 40.9 yr., 58.5% males. Average dose at the 50% isodose line was 20.3 Gy (range 16 to 26.4 Gy). Obliteration was observed in 87.8% by MRI, CT, or DSA. Not all obliteration was confirmed by DSA. Complications occurred in 12 of 59 (20.3%) patients, and in 11 of 41 (26.8%) with 3 year follow-up. Major (temporary) complications for the 59 included symptomatic cerebral edema (7), seizure (2), and hemorrhage (1). Major permanent complications occurred in one patient suffering a cranial nerve V deafferentation, and in two patients suffering a hemorrhage. GKS for cerebral AVM's offers an effective and safe method of treatment, with low permanent complication rate.

Utility and the Limit of Motor Evoked Potential Monitoring for Preventing Complications in Surgery for Cerebral Arteriovenous Malformation

To evaluate the usefulness of motor evoked potential (MEP) monitoring and mapping in arteriovenous malformation surgery. Intraoperative MEP monitoring was performed in 21 patients whose AVMs were located near the motor area or fed by arteries related to the corticospinal tract to detect blood flow insufficiency and/or direct injury to the corticospinal tract and/or to map the motor area. In 4 of 16 patients monitored for blood flow insufficiency, the MEP changed intraoperatively. In 2 patients, the changes were attributable to temporary occlusion of the feeding artery (anterior choroidal or lenticulostriate artery): 1 patient had a venous infarction around the internal capsule caused by thrombosis of the draining vein and the other bled intraoperatively from the nidus. In 17 patients, the MEP was monitored to rule out direct injury. In 1 patient, the MEP changed on coagulation of fragile vessels around the nidus in the precentral gyrus; it recovered after coagulation was discontinued. In 1 of 5 patients with MEP changes, the MEP did not recover; permanent hemiparesis developed in this patient because of venous infarction. In 1 of 11 patients subjected to MEP mapping of the motor area, we found translocation to the postcentral sulcus. In arteriovenous malformation surgery, MEP monitoring facilitates the detection of blood flow insufficiency and/or direct injury of the corticospinal tract and mapping of the motor area. It contributes to reducing the incidence of postoperative motor paresis.

Outcome after hemorrhage following Gamma Knife surgery for cerebral arteriovenous malformations

Although the effects of Gamma Knife surgery (GKS) on the risk of hemorrhage are poorly understood, a certain subset of patients does suffer bleeding after GKS. This study was undertaken to analyze the outcome of patients sustaining hemorrhage after GKS; it is the most feared complication of radiosurgical management of cerebral arteriovenous malformations (AVMs). Between May 1997 and June 2006, 494 cerebral AVMs in 489 patients were treated using a Leksell Gamma Knife Model B, and follow-up evaluations were conducted until June 2007 at the All India Institute of Medical Sciences in New Delhi. Fourteen patients who sustained a hemorrhage after GKS formed the study group. In most of these patients conservative management was chosen. The mortality rate was 0% and there was a 7% risk of sustaining a severe deficit following rebleeding after GKS. None of the patients sustained rebleeding after complete obliteration. Patients with Spetzler-Martin Grade III or less had increased chances of hemorrhage after GKS (p < 0.002). The presence of deep venous drainage, aneurysm, venous hypertension, or periventricular location on angiography was common in patients with hemorrhage after GKS. The risk of hemorrhage that remains following GKS for cerebral AVMs is highest in the 1st year after treatment. The present study showed a relatively good outcome even in cases with hemorrhage following GKS, with no deaths and minimal morbidity, further substantiating the safety and efficacy of the procedure.

Gamma Knife surgery for cerebral arteriovenous malformations in children: a 13-year experience

Studies on the efficacy of arteriovenous malformation (AVM) radiosurgery have largely been conducted in the adult population. Clinically, the results may not always be applicable to pediatric patients. Moreover, studies involving the pediatric population have largely comprised small- (< 3 cm3) and medium-sized (3-10 cm3) AVMs. For large (> 10 cm3) AVMs in children, sparse radiosurgical results are available. The current study was conducted to further clarify the role of radiosurgery in the treatment of pediatric AVMs. A retrospective analysis was performed of data obtained in 105 pediatric patients (< 18 years of age) with cerebral AVMs treated by Gamma Knife surgery (GKS) between 1993 and 2006. For statistical comparison the authors studied data acquired in 458 adult patients with AVMs treated during the same period. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Cerebral angiography was used to confirm the obliteration of the AVM. In pediatric patients, the AVM obliteration rate at 48 months after a primary GKS was 65%. Repeated GKS in those in whom primary treatments failed further ablated some AVMs, for an overall obliteration rate of 81%. The efficacy of GKS correlated with the size of the AVM: 91% for small, 86% for medium, and 64% for large AVMs. The treatments were associated with an 8% morbidity rate and < 1% mortality rate. Posttreatment hemorrhage occurred in 4 (4%) of 105 patients. Obliteration rates at 48 months of small and extremely large (> 20 cm3) AVMs were similar in the pediatric and adult groups, whereas AVMs between 3 and 10 cm3 responded less efficaciously in children (p = 0.042). The AVMs with volumes ranging from 10 to 20 cm3 were also associated with a lower obliteration rate in children at 48 months, but statistical significance was not reached (p = 0.279). Gamma Knife surgery is an effective and safe treatment alternative for pediatric AVMs. The medium (3-10-cm3) and large (10-20-cm3) AVMs tend to respond less efficaciously than those of comparable size in adults.

Early Experience with 3-T Magnetic Resonance Tractography in the Surgery of Cerebral Arteriovenous Malformations in and around the Visual Pathway

To evaluate of the role of magnetic resonance (MR) tractography on the optic radiation with a 3-T MR unit in the surgery of cerebral arteriovenous malformation (AVM) in and around the visual pathway. Of the 322 patients with cerebral AVMs admitted to our clinic between 1978 and 2005, a study of MR tractography was made on 29 patients. Ten of those patients had AVMs in and around the visual pathway and were included in this study. There were two men and eight women ranging in age from 15 to 64 years (mean age, 34.5 +/- 14.8 yr). All of the patients underwent 3-T tractography of optic radiation (OR) and neuro-ophthalmologic evaluation. Four of the 10 patients underwent surgical resection of the AVM. A postoperative 3-T MR study and a neuro-ophthalmologic evaluation was performed 1 month after surgery in most patients. The preoperative patients for whom tractography demonstrated a continuous bundle of OR from the medial temporal region to the primary visual cortex had minimal or no visual field loss, whereas the patients for whom the tractography did not show a continuous bundle of OR had significant visual loss. The patients for whom tractography in the postoperative study demonstrated a bundle of OR experienced no postoperative deterioration of the visual field loss, whereas the patients for whom tractography did not demonstrate a bundle of OR exhibited significant visual field loss. This technique is thought to be useful in confirming the integrity of and localizing deviated tract and in evaluating the surgical risk, especially for nonhemorrhagic AVMs in and around the visual pathways, taking some limitations of this method into consideration.

Application of intraoperative real-time ultrasound in the surgical treatment of cerebral arteriovenous malformation

To investigate the value of intraoperative real-time ultrasound during surgery of cerebral arteriovenous malformations (AVMs). Thirteen patients with cerebral AVMs, 12 supratentorial and 1 infratentorial, underwent microsurgical treatment. Intraoperative ultrasound (IOUS) with multimodality was performed before the starting of resection in order to: (1) localize and delineate the AVM, (2) differentiate the embolized and perfused parts of AVM, and (3) identify the feeding arteries and draining veins. After removal of the lesion, sonographic examination was repeated to detect the residual AVM tissue and the findings were compared with the intra- and/or post-operative angiographic finding. Total resection was achieved in all 13 patients with AVM under real-time ultrasonographic navigation. The niduses of AVM were localized and defined precisely by IOUS due to their dichromatic flow pattern. The embolized parts of AVM exhibited hyperechogenicity without blood signals. The feeding and draining vessels were distinguished from normal ones morphologically and hemodynamically. Complete removal of the AVM determined sonographically was then confirmed by angiography. Intraoperative real-time ultrasound allows accurate localization and navigation of the cerebral AVMs, provides valuable information during surgery, and helps determine the degree of removal of the cerebral AVM.

A simple method for predicting imaging-based complications following gamma knife surgery for cerebral arteriovenous malformations

Object. The authors studied the relationship between dose planning parameters and complications in the treatment of cerebral arteriovenous malformations (AVMs). Methods. There were 41 continuous unselected patients. The mean follow-up period was 19 months; the mean age was 28 years; the male/female ratio was 2.2:1.0; the median prescription dose was 25 Gy (range 14–25 Gy); the median prescription isodose was 50%. The median lesion volume was 4.4 cm3. The median lesion coverage was 93%; and the mean conformity index was 1.22. The authors found no relationship between lesion volume or integral dose and the development of the clinical effects based on the adverse radiation effects (AREs); however, there was a significant relationship between both target volume and integral dose with the development of AREs as well as the severity of the AREs. Conclusions. The integral dose could be used as a guideline for the prescription dose. Arguments are made for maximizing the prescription dose for the long-term safety of the patient.

A simple method for predicting imaging-based complications following gamma knife surgery for cerebral arteriovenous malformations

The authors studied the relationship between dose planning parameters and complications in the treatment of cerebral arteriovenous malformations (AVMs). There were 41 continuous unselected patients. The mean follow-up period was 19 months; the mean age was 28 years; the male/female ratio was 2.2:1.0; the median prescription dose was 25 Gy (range 14-25 Gy); the median prescription isodose was 50%. The median lesion volume was 4.4 cm3. The median lesion coverage was 93%; and the mean conformity index was 1.22. The authors found no relationship between lesion volume or integral dose and the development of the clinical effects based on the adverse radiation effects (AREs); however, there was a significant relationship between both target volume and integral dose with the development of AREs as well as the severity of the AREs. The integral dose could be used as a guideline for the prescription dose. Arguments are made for maximizing the prescription dose for the long-term safety of the patient.

Effect of a single high-dose gamma irradiation on cultured cells in human cerebral arteriovenous malformation

Object. The purpose of this study was to analyze the effect of single high-dose gamma irradiation at a cellular biological level on tissue cultures obtained in patients who underwent surgery for cerebral arteriovenous malformation (AVM). Methods. The cell proliferation indices and changes in activation of p53, p21Waf-1, and mdm-2 were determined. Additionally, immunohistochemical investigations for vimentin, desmin, α—smooth muscle actin (α-SMA), glial fibrillary acidic protein, Factor VIII—related antigen (F-VIII), cytokeratin, S100, and transforming growth factor—β (TGFβ) were performed on cultured AVM cells after a single high-dose irradiation. Normal human brain microvessel endothelial (HBE) cells and aortic smooth muscle cells served as controls. The proliferation index decreased on the 5th day after irradiation and remained depressed over the observation period in the irradiated AVM cultures. The p53, p21Waf-1, and mdm-2 messenger RNA measurements showed considerable elevation both in AVM cultures and HBE cells after 15-Gy irradiation, which indicated apoptosis. Immunohistochemistry revealed strong vimentin positivity in the nonirradiated cultures, which gradually decreased in the irradiated cultures. Transforming growth factor—β positivity was demonstrated in the irradiated specimens, indicating transformation of fibroblastic cells into activated myofibroblastic elements. This transformation was confirmed by demonstrating elevated SMA expression as well in the radiation-treated fibroblasts. Conclusions. The presence of TGFβ and α-SMA activity in the irradiated AVM cells suggests that along with the genetically confirmed apoptotic activity, fibroblast transformation into myofibroblasts might be one of the mechanisms leading to shrinkage and obliteration of AVMs after single high-dose gamma irradiation.