First use of radiation for the treatment of arteriovenous malformation.

In 1921, Norwegian neurosurgeon Vilhelm Magnus (1871-1929) described the first use of radiation for the treatment of an arteriovenous malformation (AVM) in his monograph, Bidrag til hjernechirurgiens klinik og resultater. Seeing as this monograph has never been widely translated nor digitized, the authors discuss the impact of Magnus' original work and the ethics surrounding its citation. The senior author of this paper gained access to and directly translated key sections of Magnus' publication. Without Norwegian language skills, reading and understanding Magnus' text would have been impossible. Magnus described the use of radiation therapy in a single patient found to have an AVM (or "angioma"). He states that she was "well" 8 years later. No other information on that treatment is given, but for good reason Magnus has been given credit in the literature for the first use of radiation of any kind to treat a person with AVM. Most papers that have referenced Magnus' monograph cite it even though it is probable that the authors did not see it, let alone read its contents. While it is appropriate that his innovation has been properly credited, the authors discuss the limits of citing publications sight unseen.

Good response to pulsed dye laser in patients with capillary malformation-arteriovenous malformation syndrome (CM-AVM).

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by heterozygous mutations in RASA1 and EPHB4. Capillary stains in CM-AVM are compatible with Schöbinger's phase I AVMs. Vascular laser has been classically contraindicated for the treatment of AVMs, as there is a fear of accelerating their progression. In this study, we have treated capillary stains in five CM-AVM patients with pulsed dye laser, with improvement and without worsening or recurrence of the lesions after 1 year of clinical and ultrasound follow-up.

Radiation Therapy for Benign Disease: Arteriovenous Malformations, Desmoid Tumor, Dupuytren Contracture, Graves Ophthalmopathy, Gynecomastia, Heterotopic Ossification, Histiocytosis.

Although the use of ionizing radiation in malignant conditions has been well established, its application in benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, in instances where the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the current use of radiation therapy in some of the more common benign conditions.

Stereotactic radiosurgery and fractionated radiotherapy for spinal arteriovenous malformations - A systematic review of the literature.

Spinal arteriovenous malformations (AVMs) comprise a group of complex vascular lesions whose treatment with microsurgery or transarterial embolization can be challenging. Stereotactic radiosurgery is a well-established treatment for intracranial AVMs, and spinal radiosurgery and fractionated radiotherapy are common treatments for spinal tumors of both primary and metastatic origin. The use of radiosurgery and fractionated radiotherapy for the treatment of spinal arteriovenous malformations, however, has been infrequently reported. Spinal stereotactic radiosurgery is emerging as a promising option for the treatment of these lesions. We conducted a systematic review of English language articles reporting one or more cases of spinal radiosurgery or fractionated radiotherapy for the treatment of spinal arteriovenous fistulas (AVFs) or arteriovenous malformations. Eight unique studies comprising 64 patients were identified. All treated lesions consisted primarily of spinal AVMs, either intramedullary or metameric. Most were treated with CyberKnife technology. Marginal doses in the most current studies ranged from 18 to 21 Gy given over 2-4 fractions. In aggregate, good outcomes were reported in 92.2% with no instances of post-treatment hemorrhage over a mean follow-up time of 46.8 months. Angiographic follow-up showed the nidus to be obliterated in 16%, decreased in 44.6%, and unchanged in 39.3%. Stereotactic radiosurgery for spinal arteriovenous malformations holds promise as a safe and potentially effective option in the treatment of these rare but complex lesions.

Diode laser to treat small oral vascular malformations: A prospective case series study.

OBJECTIVE: The current work examined a consecutive series of patients presenting vascular malformations (VMs) and venous lakes (VLs) of the lip and oral mucosa who were treated with transmucosal diode laser applications and assessed over a 1 year period. STUDY DESIGN AND METHODS: Fifty-nine patients (31 males and 28 females) presenting low-flow VMs or VLs of the oral cavity were treated transmucosally using a diode laser (with an 830 nm operating wavelength and 1.6 W output power) with a 320 µm diameter flexible fiber. All the lesions were assessed 7 days, 30 days, and 1 year after the laser treatment, and the lesion reduction percentage was scored on a one to five scale. The patients were also asked to assess their pain perception daily during the 7 days following the treatment using a visual analog scale (VAS). RESULTS: There were no procedure-related intra- or post-operative complications; only modest pain intensity was reported. Thirty days after the treatment, lesion reduction was described as excellent or good in 52 cases; it was fair or poor in 7. Six patients (F:M ratio 2:4) required a second diode laser application. At the 1 year follow-up, volume reduction was complete in 48 out of 59 patients; there were five recurrences (F:M ratio 3:2). No relevant gender-related differences were noted. CONCLUSION: The use of diode laser application to treat small oral VMs and VLs was associated to shorter operating times and fewer postoperative complications with respect to the scapel surgery approach. More than one session may nevertheless be required if the anomaly is larger than 10 mm. Lasers Surg. Med. 50:111-116, 2018. © 2017 Wiley Periodicals, Inc.

Evaluation of Clinical Application and Dosimetric Comparison of Treatment Plans of Gamma Knife and CyberKnife in Treating Arteriovenous Malformations.

PURPOSE: To analyze and compare the characteristics of dose distributions for Leksell Gamma Knife Perfexion (LGK-PFX) and CyberKnife (CK) in treating arteriovenous malformations (AVMs). SUBJECTS AND METHODS: Twenty-four patients with AVMs who received CK radiosurgery at a prescribed dose (PD) of 16-25 Gy in a single fraction were selected. A LGK-PFX treatment plan with the same PD was designed for each patient. Dosimetric values for both systems were compared with respect to the conformity index (CI); selectivity index (SI); gradient index (GI) of 75, 50, and 25% of the PD; heterogeneity index; volume of the brain tissue covered by doses of 10 and 12 Gy; maximum dose delivered to the brainstem; and beam-on time. RESULTS: The CIs of LGK-PFX and CK were 0.744 ± 0.075 and 0.759 ± 0.071 (p = 0.385), respectively. The SIs of LGK-PFX and CK were 0.764 ± 0.081 and 0.780 ± 0.076 (p = 0.424), respectively. The GI75%, GI50%, and GI25% values of LGK-PFX and CK were 1.028 ± 0.123 and 2.439 ± 0.338 (p < 0.001), 3.169 ± 0.265 and 4.972 ± 0.852 (p < 0.001), and 8.650 ± 0.914 and 14.261 ± 2.476 (p < 0.001), respectively. Volumes of the brain tissue covered by 10 Gy and 12 Gy for LGK-PFX and CK (p < 0.001) exhibited a significant difference. CONCLUSIONS: LGK-PFX and CK exhibited similar dose conformity. LGK-PFX showed superior normal tissue sparing.

Radiosurgical ablation of spinal cord arteriovenous malformations.

Spinal cord arteriovenous malformations (SCAVMs) are rare entities that account for less than 20% of spinal masses. These lesions represent a unique clinical challenge, in that surgical or endovascular treatment is often associated with devastating functional consequences. Over the past few decades, radiosurgery has become a well-established treatment modality for SCAVMs, and may be a first-line treatment in many patients afflicted with this devastating disease. This chapter summarizes the data available regarding radiosurgical treatment of SCAVMs.

Radiosurgery Alters the Endothelial Surface Proteome: Externalized Intracellular Molecules as Potential Vascular Targets in Irradiated Brain Arteriovenous Malformations.

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs) that drives blood vessel closure through cellular proliferation, thrombosis and fibrosis, but is limited by a delay to occlusion of 2-3 years and a maximum treatable size of 3 cm. In this current study we used SRS as a priming tool to elicit novel protein expression on the endothelium of irradiated AVM vessels, and these proteins were then targeted with prothrombotic conjugates to induce rapid thrombosis and vessel closure. SRS-induced protein changes on the endothelium in an animal model of AVM were examined using in vivo biotin labeling of surface-accessible proteins and comparative proteomics. LC-MS/MS using SWATH acquisition label-free mass spectrometry identified 280 proteins in biotin-enriched fractions. The abundance of 56 proteins increased after irradiation of the rat arteriovenous fistula (20 Gy, ≥1.5-fold). A large proportion of intracellular proteins were present in this subset: 29 mitochondrial and 9 cytoskeletal. Three of these proteins were chosen for further validation based on previously published evidence for surface localization and a role in autoimmune stimulation: cardiac troponin I (TNNI3); manganese superoxide dismutase (SOD2); and the E2 subunit of the pyruvate dehydrogenase complex (PDCE2). Immunostaining of AVM vessels confirmed an increase in abundance of PDCE2 across the vessel wall, but not a measurable increase in TNNI3 or SOD2. All three proteins co-localized with the endothelium after irradiation, however, more detailed subcellular distribution could not be accurately established. In vitro, radiation-stimulated surface translocation of all three proteins was confirmed in nonpermeabilized brain endothelial cells using immunocytochemistry. Total protein abundance increased modestly after irradiation for PDCE2 and SOD2 but decreased for TNNI3, suggesting that radiation primarily affects subcellular distribution rather than protein levels. The novel identification of these proteins as surface exposed in response to radiation raises important questions about their potential role in radiation-induced inflammation, fibrosis and autoimmunity, but may also provide unique candidates for vascular targeting in brain AVMs and other vascular tissues.

Limitations of analytical dose calculations for small field proton radiosurgery.

The purpose of the work was to evaluate the dosimetric uncertainties of an analytical dose calculation engine and the impact on treatment plans using small fields in intracranial proton stereotactic radiosurgery (PSRS) for a gantry based double scattering system. 50 patients were evaluated including 10 patients for each of 5 diagnostic indications of: arteriovenous malformation (AVM), acoustic neuroma (AN), meningioma (MGM), metastasis (METS), and pituitary adenoma (PIT). Treatment plans followed standard prescription and optimization procedures for PSRS. We performed comparisons between delivered dose distributions, determined by Monte Carlo (MC) simulations, and those calculated with the analytical dose calculation algorithm (ADC) used in our current treatment planning system in terms of dose volume histogram parameters and beam range distributions. Results show that the difference in the dose to 95% of the target (D95) is within 6% when applying measured field size output corrections for AN, MGM, and PIT. However, for AVM and METS, the differences can be as great as 10% and 12%, respectively. Normalizing the MC dose to the ADC dose based on the dose of voxels in a central area of the target reduces the difference of the D95 to within 6% for all sites. The generally applied margin to cover uncertainties in range (3.5% of the prescribed range + 1 mm) is not sufficient to cover the range uncertainty for ADC in all cases, especially for patients with high tissue heterogeneity. The root mean square of the R90 difference, the difference in the position of distal falloff to 90% of the prescribed dose, is affected by several factors, especially the patient geometry heterogeneity, modulation and field diameter. In conclusion, implementation of Monte Carlo dose calculation techniques into the clinic can reduce the uncertainty of the target dose for proton stereotactic radiosurgery. If MC is not available for treatment planning, using MC dose distributions to adjust the delivered doses level can also reduce uncertainties below 3% for mean target dose and 6% for the D95.

Coexistent arteriovenous malformation and hippocampal sclerosis.

Cavernous angiomas or cavernomas have been occasionally described in patients presenting with medically intractable epilepsy. Reports of cavernomas associated with a second pathology potentially causative of seizures have rarely been documented; most commonly, the second pathology is focal cortical dysplasia or less frequently, hippocampal sclerosis. To our knowledge, cases of arteriovenous malformation arising in this clinical setting and associated with hippocampal sclerosis have not been previously described. We report a 56-year-old woman who initially presented at age 24years with staring spells. Imaging studies revealed an arteriovenous malformation in the right parietal lobe. At age 51years, she represented with signs and symptoms related to a hemorrhage from the malformation. The patient underwent Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden) of the lesion. She subsequently developed seizures, refractory to medical management. MRI studies showed atrophy in the right hippocampus. She underwent resection of the right parietal lobe and hippocampus. Histopathologic examination of the right parietal lesion revealed an arteriovenous malformation marked by focally prominent vascular sclerosis, calcification and adjacent hemosiderin deposition. The hippocampus was marked by prominent neuronal loss and gliosis in the CA1 region, consistent with CA1 sclerosis or hippocampal sclerosis International League Against Epilepsy type 2.

First 1,000 Cases of Gamma Knife Surgery for Various Intracranial Disorders in LSU Health-Shreveport: Radiological and Clinical Outcome.

OBJECTIVE: Gamma knife radiosurgery (GKRS) has emerged as an important therapeutic alternative for different intracranial lesions. We have reviewed our institution's first 1,000 cases of radiosurgeries. MATERIALS AND METHODS: We performed a retrospective review (2000-2013) of 1,017 radiosurgeries in 911 patients with various intracranial lesions including vestibular schwannoma (82), meningioma (136), metastatic brain tumors (298), astrocytoma (49), pituitary adenoma (92), arteriovenous malformation (85) and trigeminal neuralgia (169). RESULTS: GKRS in different intracranial lesions showed significant variations in outcome and complications. Overall, the local tumor growth control for benign and malignant tumors was 89 percent and 70 percent respectively. The rate of obliteration of arteriovenous malformation nidus was 79 percent. The complete and partial relief of pain in the patients with trigeminal neuralgia was 55.6 percent and 22.4 percent respectively. CONCLUSION: At recent follow-up, GKRS showed good control of different tumor growth, obliteration of AVM nidus and remission of trigeminal neuralgia pain, good overall and progression free survival rate, possible preservation of neurological functions, lesser number of complications, and improvement of quality of life. Therefore, GKRS is an important treatment option for patients with different benign intracranial tumors, AVM and trigeminal neuralgia. However, GKRS is not effective for recurrent malignant tumors in the brain.

Surgical management of combined intramedullary arteriovenous malformation and perimedullary arteriovenous fistula within the hybrid operating room after five years of performing focus fractionated radiotherapy: case report.

Perimedullary arteriovenous fistula (AVF) shunts occur on the spinal cord surface and can be treated surgically or by endovascular embolization. In contrast, the nidus of an intramedullary arteriovenous malformation (AVM) is located in the spinal cord and is difficult to treat surgically or by endovascular techniques. The benefits of radiotherapy for treating intramedullary AVM have been published, but are anecdotal and consist largely of case reports. We present a case of combined cervical intramedullary AVM and perimedullary AVF which received surgical treatment within a hybrid operating room (OR) after 5 years of focus fractionated radiotherapy. A 37-year-old male presented with stepwise worsening myelopathy. Magnetic resonance imaging and spinal angiography revealed intramedullary AVM and perimedullary AVF at the C3 to C5 levels. In order to reduce nidus size and blood flow, we first performed focal fractionated radiotherapy. Five years later, the lesion volume was reduced. Following this, direct surgery was performed by an anterior approach using corpectomy in the hybrid OR. The spinal cord was monitored by motor-evoked potential throughout the surgery. Complete obliteration of the fistulous connection was confirmed by intraoperative indocyanine green video-angiography and intraoperative angiography, preserving the anterior spinal artery. We conclude that surgical treatment following focal fractionated radiotherapy may become one strategy for patients who are initially deemed ineligible for endovascular embolization and surgical treatment. Furthermore, the hybrid OR enables safe and precise treatment for spinal vascular disorders in the fields of endovascular treatment and neurosurgery.

Concurrent pancreatic head and tail arteriovenous malformations in a 40-year-old gentleman: the first published report.

CONTEXT: Pancreatic arteriovenous malformations (AVMs) are uncommon in the gastrointestinal tract. Less than 100 cases have been identified in the medical literature. Approximately 10% of all pancreatic AVMs are sporadic. CASE REPORT: Herein, we report the first documented case of sporadic concurrent pancreatic head and tail AVMs in a 40-year-old gentleman who presented with a 10-day history of epigastric pain and one episode of hematemesis. Patient denied any history of traumatic incidents, cigarette smoking, alcohol abuse, chronic gastric/duodenal ulcer, chronic pancreatitis, chronic hepatic disease, difficulty swallowing, respiratory compromise, or weight loss. Physical examination and laboratory results were unremarkable. Contrast-enhanced computed tomography scan showed two hypervascular masses involving the pancreatic head and tail. The celiac trunk angiogram showed proliferating vascular networks involving the pancreatic head and tail. The superior mesenteric angiogram demonstrated significant vascular contribution to the pancreatic head arteriovenous malformation only. Due to the extreme locations of pancreatic AVMs in the head and tail, surgical resection of both lesions (leaving behind the normal pancreatic body) was not possible. Instead, patient underwent intraoperative irradiation therapy (IORT). During the procedure, patient was surgically operated to retract healthy organs/tissues, and then a single concentrated dose of radiation therapy was precisely applied to both pancreatic head and tail AVM lesions. Patient had an uneventful postoperative recovery and was discharged home on the second postoperative day in stable condition. The patient is to be seen in clinic in a 4-month-period during which patient will be completing a 12-month period of postoperative IORT. CONCLUSION: This is the first documented case of sporadic concurrent pancreatic head and tail AVMs. Angiography is the gold standard diagnostic modality.

External beam radiotherapy for angiographically diagnosed arteriovenous malformation involving the entire pancreas.

Ultrasonography of a 66-year-old man with abdominal discomfort detected an abnormality of the pancreas. Multiphase contrast-enhanced computed tomography (CT) and angiography revealed arteriovenous malformation (AVM) involving the entire pancreas. The large number of dilated and tortuous feeding arteries contraindicated surgical resection or transcatheter embolization. Hemorrhage into the main pancreatic duct occurred 1 month after diagnosis. The patient underwent external radiotherapy with a total dose of 44 Gy following a conventional fractionation schedule of 2 Gy daily for 22 days administered 5 days per week. Contrast-enhanced CT after treatment confirmed disappearance of feeding vessels and nidi with no complication. Evidence of recurrence was not detected on contrast-enhanced CT 6 months after irradiation.

Temporary alopecia after embolization of an arteriovenous malformation.

Alopecia after head and neck radiotherapy has been extensively reported in the literature. However, alopecia after endovascular procedures is seldom reported in the dermatological literature. Prolonged fluoroscopic imaging during these procedures may cause serious radiation injuries to the skin, such as dermatitis or alopecia. Radiation-induced temporary alopecia is a peculiar form of radiodermitis that occurs over the areas of the scalp that receive the highest doses of radiation. Although repopulation of alopecic patches occurs spontaneously without treatment, it is important to recognize this disorder to establish a correct diagnosis and inform patients about this transient side effect. We report a 44-year-old woman presenting with temporary alopecia after embolization of an arteriovenous malformation.

Role of external beam radiotherapy for arteriovenous malformation of the pancreas.

Pancreatic arteriovenous malformation (PAVM) is rare and is mainly reported from Asian countries. We incidentally encountered an asymptomatic, early-stage PAVM in a patient who presented with portal venous distention, Child B liver cirrhosis, and hepatoma. The PAVM had multiple feeding arteries and drainage into the portal vein and varices. Because surgery was not indicated, after considering the risks and bene-fits the patient chose treatment with 40 Gy of conformal radiotherapy for 4 weeks. Computed tomography performed 6 months later revealed reduction in the size of the PAVM. Treatment had lasting effects for 18 months without significant toxicity. As observed in many reports of radiotherapy for various AVMs, the radiotherapy may stall self-augmenting growth of the AVM. Conventional fractionated radiotherapy of 40 Gy may be a useful choice for early-stage PAVM.

[Clinical application of radiotherapy for the treatment of giant vascular malformations in oral and maxillofacial region].

OBJECTIVE: To discuss the clinical use of radiotherapy in the treatment of giant vascular malformation. METHODS: Six patients with giant vascular malformation in oral and maxillofacial region were treated by three dimensional radiation therapy in Department of Stomatology, The Second Affiliated Hospital, School of Medicne, Zhejiang University in the last ten years and the cilinical data were reviewed. The treatment results were evaluated by clinical examination and radiology. RESULTS: No complication was observed during and after the radiotherapy. All patients were satisfied with the aesthetic results. The lesions in MRI were all reduced and even disappeared. There was no sign of recurrence during the follow-up period. CONCLUSIONS: Three dimensional radiotherapy is safe and effective for oral and maxillofical vascular malformation.

Stereotactic radiotherapy and radiosurgery in pediatric patients: analysis of indications and outcome.

INTRODUCTION: We describe indications, outcomes, and risk profiles of fractionated stereotactic radiotherapy (SRT) and single fraction "radiosurgery" (SRS) in pediatric patients compared to the adult population and evaluate the causal role of SRS and SRT in inducing new neurological complications. MATERIALS AND METHODS: Six children with AVMs and 12 children with neoplastic diseases were prospectively followed for >2 years after SRT/S. The survival, control of pathology, and specified neurological complications were analyzed. In tumor patients, the median overall survival time was 45 months (range 5-103) and the median progression free survival time was 35 months (range 5-98). RESULTS: Control or regression of the tumor was obtained in 83% of patients with neoplastic disease. Three patients with malignant tumors died from disease progression. In AVMs the median time follow up was 52 months (range 27-100). All AVMs were obliterated. New neurological deficits occurred in 67%. SRT/S was considered the direct cause in 25%. All the neurological deficiencies related to SRT/S were focal and related to the irradiated areas. In tumor patients, midline lesions, malignant diagnosis, and additional treatment with surgery, chemotherapy, and craniospinal irradiation seemed to increase the risk of new deficits after SRT/S. In AVM patients, a high Spetzler-Martin grade seemed to carry a higher complication risk. CONCLUSION: The risk of uncontrolled tumor disease or the risk of hemorrhage of non-obliterated AVM must be balanced against the overall risks and benefits of SRT/S. Following SRT/S, the risk of worsening pre-existing deficits is relatively high. The risk of inducing new long-term deficits is relatively low.

Assessment of the alpha/beta ratios for arteriovenous malformations, meningiomas, acoustic neuromas, and the optic chiasma.

PURPOSE: To determine alpha/beta (alpha/beta) values of arteriovenous malformations (AVM), meningiomas, acoustic neuromas (AN), and the optic chiasma using clinical data. METHODS AND MATERIALS: Data of dose/fractionation schedules form the literature, iso-effective for a specific clinical outcome, were analysed using the Fraction Equivalent plot (FE) method and the Tucker method. Established safe dose/fractionation schedules for the optic chiasma were used to determine its alpha/beta value. RESULTS: With the FE plot method, an alpha/beta value of 3.76 Gray (Gy) (95% confidence level [CL]: 2.8-4.6 Gy) for meningiomas, 2.4 Gy (95% CL: 0.8-3.9 Gy) for acoustic neuroma, and 14.7 Gy (95% CL: 3.8-25.7 Gy) for arteriovenous malformations were determined. The respective alpha/beta values using the Tucker method were 3.3 Gy (95%CL: 2.2-6.8 Gy), 1.77 Gy (95%CL: 1.3-3.0 Gy) and -57 Gy (95%CL: -79.6 to -35.2 Gy). No meaningful alpha/beta values could be determined for the optic chiasma. CONCLUSION: Acoustic neuromas with a low alpha/beta value would show no lesion intrinsic benefit from fractionation. Meningiomas probably benefit from a hypofractionated schedule. The high alpha/beta value for AVM can be explained but needs further research. Fractionation versus radiosurgery can be considered when the primary objective is to avoid normal tissue damage.