期刊
JOURNAL OF NEUROLOGY
卷 261, 期 4, 页码 732-737出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-014-7260-8
关键词
AVM; ALS; Embolization; Amyotrophic lateral sclerosis; Arterioveneous malformation
Cerebral arterioveneous malformations (AVM) can cause neurological symptoms and carry a risk of hemorrhage. Therapeutic options to cure or reduce AVM include surgery, embolization, irradiation, and combinations thereof. Prompted by three index cases treated in our center, we studied whether AVM embolization is associated with an increased risk of subsequent amyotrophic lateral sclerosis (ALS). In a monocenter series, we retrospectively analyzed the new development of ALS in patients who had been treated with embolization of cerebral AVM from 1986 to 2010 (n = 1,114). After a median follow-up of 11 years (range, 0-25 years) after first embolization, seven patients developed ALS with a median latency of 14 years (range, 12-17 years) and a median age of ALS onset of 38 years (range, 28-52 years). In all cases, the initial limb of ALS symptom onset was ipsilateral to the AVM. Five patients died within the follow-up period, with a range of 1-4 years after the onset of ALS symptoms. The seven patients belonged to a subgroup of 34 patients who had in common a rare AVM architecture characterized by significant perinidal angiogenesis. All cases were partially treated by at least three embolization sessions. As there is no known association between AVM and ALS, AVM embolization must be taken into account to have contributed to the development of ALS in the seven patients with this rare AVM architecture. Searching for underlying mechanisms, we compared frozen serum samples that were available from four of the patients who developed ALS, from eight patients with AVM of other architecture, and less than three embolizations who did not develop ALS, and of 20 controls. The concentration of vascular endothelial growth factor (VEGF) in the serum was lowest in AVM patients who developed ALS (245 +/- A 154 pmol/l) and highest in controls (409 +/- A 178 pmol/l). Although this difference was not statistically significant in the small sample, it suggests that low VEGF production by AVM with significant angiogenesis, possibly due to multiple embolization procedures, might have contributed to ALS development. ALS should be considered as a late complication of multiple embolizations of cerebral AVM characterized by significant perinidal angiogenesis.
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