Ding Dale, Yen Chun-Po, Starke Robert M, Xu Zhiyuan, Sheehan Jason P
University of Virginia, Department of Neurological Surgery, Charlottesville, Va., USA.
Cerebrovasc Dis. 2015;39(1):53-62. doi: 10.1159/000369959. Epub 2014 Dec 24.
Intracerebral hemorrhage is simultaneously the most frequent and most debilitating manifestation of intracranial arteriovenous malformations (AVM), but its impact on success and complications of radiosurgery has not been rigorously assessed. In this case-control study, we define the effect of prior hemorrhage on AVM radiosurgery outcomes.
From a prospective, institutional database of 1,400 AVM patients treated with Gamma Knife radiosurgery, unruptured and ruptured AVMs were matched in a 1:1 fashion, blinded to outcome, based on patient demographics, prior embolization (26.6% of each cohort), AVM size (mean volume of unruptured AVMs 3.7 cm(3) versus ruptured AVMs 3.5 cm(3), p = 0.195), Spetzler-Martin grade (Grade I 17.0%, Grade II 37.8%, Grade III 34.8%, Grade IV 10.4% for each cohort), and radiosurgical treatment parameters (mean prescription dose for unruptured AVMs 20.9 Gy versus ruptured AVMs 21.0 Gy, p = 0.837). There were 270 patients in each cohort. Matched statistical analyses were used to compare the baseline characteristics, obliteration rates, post-radiosurgery latency period hemorrhage risks, and incidences of radiation-induced changes (RIC) between the two cohorts.
The actuarial obliteration rates of the two cohorts were similar (unruptured AVMs: 38, 58, and 76% at 3, 5, 10 years, respectively; ruptured AVMs: 40, 60, and 73% at 3, 5, 10 years, respectively; p = 0.592). However, for embolized AVMs, complete obliteration was more likely to be achieved in unruptured lesions (unruptured AVMs: 25, 32, and 54% at 3, 5, 10 years, respectively; ruptured AVMs: 18, 27, and 42% at 3, 5, 10 years, respectively; p = 0.038). Prior AVM rupture resulted in a higher annual risk of post-radiosurgery latency period hemorrhage (ruptured AVMs 2.3% versus unruptured AVMs 1.1%, p = 0.025) but a lower rate of cumulative and symptomatic RIC (cumulative RIC: ruptured AVMs 30.4% versus unruptured AVMs 48.9%, p < 0.0001; symptomatic RIC: ruptured AVMs 7.0% versus unruptured AVMs 12.2%, p = 0.041, respectively). The rates of permanent RIC were similar between the unruptured (2.2%) and ruptured (1.9%) AVM cohorts (p = 0.761). The mean time interval to onset of RIC (unruptured AVMs 13.3 months versus ruptured AVMs 12.1 months, p = 0.783), and the mean duration of RIC (unruptured AVMs 22.0 months versus ruptured AVMs 21.7 months, p = 0.599) were not significantly different between the two cohorts.
Prior AVM rupture significantly alters the risk of latency period hemorrhage and RIC following radiosurgery. These effects should be taken into consideration with the multidisciplinary management of AVM patients. Radiosurgery does not significantly alter the natural history of the hemorrhage risks of unruptured and ruptured AVMs unless obliteration is achieved.
脑出血是颅内动静脉畸形（AVM）最常见且最具致残性的表现，但尚未对其对放射外科手术成功率和并发症的影响进行严格评估。在本病例对照研究中，我们确定既往出血对AVM放射外科手术结果的影响。
从一个前瞻性机构数据库中选取1400例接受伽玛刀放射外科治疗的AVM患者，根据患者人口统计学特征、既往栓塞情况（每组26.6%）、AVM大小（未破裂AVM的平均体积为3.7 cm³，破裂AVM的平均体积为3.5 cm³，p = 0.195）、Spetzler-Martin分级（每组中I级17.0%，II级37.8%，III级34.8%，IV级10.4%）以及放射外科治疗参数（未破裂AVM的平均处方剂量为20.9 Gy，破裂AVM的平均处方剂量为21.0 Gy，p = 0.837），以1:1的方式对未破裂和破裂的AVM进行匹配，且不了解结果。每组有270例患者。采用匹配统计分析比较两组的基线特征、闭塞率、放射外科手术后延迟期出血风险以及放射性改变（RIC）的发生率。
两组的精算闭塞率相似（未破裂AVM在3年、5年和10年时分别为38%、58%和76%；破裂AVM在3年、5年和10年时分别为40%、60%和73%；p = 0.592）。然而，对于栓塞的AVM，未破裂病变更有可能实现完全闭塞（未破裂AVM在3年、5年和10年时分别为25%、32%和54%；破裂AVM在3年、5年和10年时分别为18%、27%和42%；p = 0.038）。既往AVM破裂导致放射外科手术后延迟期出血的年风险更高（破裂AVM为2.3%，未破裂AVM为1.1%，p = 0.025），但累积和有症状的RIC发生率较低（累积RIC：破裂AVM为30.4%，未破裂AVM为48.9%，p < 0.0001；有症状的RIC：破裂AVM为7.0%，未破裂AVM为12.2%，p = 0.041）。未破裂（2.2%）和破裂（1.9%）AVM组之间的永久性RIC发生率相似（p = 0.761）。两组之间RIC发作的平均时间间隔（未破裂AVM为13.3个月，破裂AVM为12.1个月，p = 0.783）以及RIC的平均持续时间（未破裂AVM为22.0个月，破裂AVM为21.7个月，p = 0.599）无显著差异。
既往AVM破裂显著改变了放射外科手术后延迟期出血和RIC的风险。在AVM患者的多学科管理中应考虑这些影响。除非实现闭塞，放射外科手术不会显著改变未破裂和破裂AVM出血风险的自然病程。
