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Bengt Karlsson, Hidefumi Jokura, Masaaki Yamamoto, Michael Söderman, and Ingmar Lax


The results of a novel radiosurgical approach to treat large arteriovenous malformations (AVMs) with repeated radiosurgery are presented and discussed.


The outcome was studied following repeated Gamma Knife surgery (GKS) for large AVMs, defined as a nidus volume of 9 ml or more. The philosophy was to treat the whole AVM with a low dose of radiation (≥ 10 Gy), and to repeat the treatment if the AVM shrank but was not obliterated. The study included 133 patients with AVMs treated at one of three different institutions. Clinical information was available for all patients, and complete radiological follow-up was available in 89 patients after the first treatment, and in 19 after the second treatment.


The estimated obliteration rate following repeated GKS was 62%. Four patients (3%) developed neurological deficits caused by the radiation, whereas five others (4%) developed cystic changes. The annual incidence of hemorrhage was high (7%), of which 35% occurred within the 1st year after the first treatment.


Repeated radiosurgery seems to be a viable option for some AVMs considered to be too large for conventional radiosurgical treatment. The incidence of posttreatment hemorrhages seems to be a larger clinical problem than radiation-induced complications.

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Bengt Karlsson, Ingmar Lax, Masaaki Yamamoto, Michael Söderman, Hidefumi Jokura, Charles Rosen, and Julian Bailes


The authors sought to assess the relationship between obliteration rate and different dose parameters following fractionated radiotherapy for arteriovenous malformations (AVMs). A comparison of the results of radiosurgery and radiotherapy for AVMs was made to calculate the best fit α/β value, which would then be used as a model for predicting the treatment outcome, independent of the number of fractions applied.


Data from 1453 patients were analyzed: 1154 treated with radiosurgery and 300 with fractionated radiotherapy. The relationships between dose and obliteration rate after 3 years were calculated, and the best fit curve to the empirical results was defined. The higher the dose per fraction, biologically effective dose, and the lower the total dose, the higher the obliteration rate. The isoeffective doses when comparing radiotherapy and radiosurgery independent of the α/β value could not be defined. The dose per fraction had the best predictive value, independent of the number of fractions.


Dose per fraction seems to be the decisive parameter for the treatment response following both radiotherapy and radiosurgery. A larger number of fractions did not increase the obliteration rate. The data indicate that higher doses per fraction should be used when irradiating AVMs.

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Bengt Karlsson, Arne V. Johansson, Huai-Che Yang, Hidefumi Jokura, Masaaki Yamamoto, Roberto Martínez-Álvarez, Jun Kawagishi, Wan-Yuo Guo, Guus Beute, David H. C. Pan, Wen-Yuh Chung, Michael Söderman, Hitoshi Aiyama, and Tseng Tsai Yeo


There is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.


The present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.


The age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25–60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.


The present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.