Translational Surgery and Vascular Diseases Centre, University of Ferrara Hospital, Ferrara, Italy.
Department of Biomedical Sciences for Health, Chair of Physical and Rehabilitation Medicine, University of Milan, Milan, Italy.
JAMA Neurol. 2018 Jan 1;75(1):35-43. doi: 10.1001/jamaneurol.2017.3825.
Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by restricted venous outflow from the brain and spinal cord. Whether this condition is associated with multiple sclerosis (MS) and whether venous percutaneous transluminal angioplasty (PTA) is beneficial in persons with MS and CCSVI is controversial.
To determine the efficacy and safety of venous PTA in patients with MS and CCSVI.
DESIGN, SETTING, AND PARTICIPANTS: We analyzed 177 patients with relapsing-remitting MS; 62 were ineligible, including 47 (26.6%) who did not have CCSVI on color Doppler ultrasonography screening. A total of 115 patients were recruited in the study timeframe. All patients underwent a randomized, double-blind, sham-controlled, parallel-group trial in 6 MS centers in Italy. The trial began in August 2012 and concluded in March 2016; data were analyzed from April 2016 to September 2016. The analysis was intention to treat.
Patients were randomly allocated (2:1) to either venous PTA or catheter venography without venous angioplasty (sham).
Two primary end points were assessed at 12 months: (1) a composite functional measure (ie, walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity) and (2) a measure of new combined brain lesions on magnetic resonance imaging, including the proportion of lesion-free patients. Combined lesions included T1 gadolinium-enhancing lesions plus new or enlarged T2 lesions.
Of the included 115 patients with relapsing-remitting MS, 76 were allocated to the PTA group (45 female [59%]; mean [SD] age, 40.0 [10.3] years) and 39 to the sham group (29 female [74%]; mean [SD] age, 37.5 [10.6] years); 112 (97.4%) completed follow-up. No serious adverse events occurred. Flow restoration was achieved in 38 of 71 patients (54%) in the PTA group. The functional composite measure did not differ between the PTA and sham groups (41.7% vs 48.7%; odds ratio, 0.75; 95% CI, 0.34-1.68; P = .49). The mean (SD) number of combined lesions on magnetic resonance imaging at 6 to 12 months were 0.47 (1.19) in the PTA group vs 1.27 (2.65) in the sham group (mean ratio, 0.37; 95% CI, 0.15-0.91; P = .03: adjusted P = .09) and were 1.40 (4.21) in the PTA group vs 1.95 (3.73) in the sham group at 0 to 12 months (mean ratio, 0.72; 95% CI, 0.32-1.63; P = .45; adjusted P = .45). At follow-up after 6 to 12 months, 58 of 70 patients (83%) in the PTA group and 22 of 33 (67%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 2.64; 95% CI, 1.11-6.28; P = .03; adjusted P = .09). At 0 to 12 months, 46 of 73 patients (63.0%) in the PTA group and 18 of 37 (49%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 1.80; 95% CI, 0.81-4.01; P = .15; adjusted P = .30).
Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS.
clinicaltrials.gov Identifier: NCT01371760.
慢性脑脊髓静脉功能不全（CCSVI）的特征是脑和脊髓的静脉流出受限。这种情况是否与多发性硬化症（MS）有关，以及静脉经皮腔内血管成形术（PTA）对 MS 和 CCSVI 患者是否有益，目前仍存在争议。
确定静脉 PTA 在 MS 和 CCSVI 患者中的疗效和安全性。
设计、地点和参与者：我们分析了 177 例复发性缓解型 MS 患者；62 例不符合条件，包括 47 例（26.6%）经彩色多普勒超声筛查未发现 CCSVI。共有 115 例患者在研究期间入组。所有患者均在意大利 6 家 MS 中心进行随机、双盲、假对照、平行组试验。试验于 2012 年 8 月开始，2016 年 3 月结束；数据分析于 2016 年 4 月至 2016 年 9 月进行。分析采用意向治疗。
患者随机分为（2:1）静脉 PTA 或无静脉血管成形术的导管血管造影（假）组。
12 个月时评估了两个主要终点：（1）综合功能测量（即步行控制、平衡、手灵巧度、残余尿量和视力）和（2）磁共振成像上新的联合脑病变的测量，包括无病变患者的比例。联合病变包括 T1 钆增强病变加上新的或扩大的 T2 病变。
包括 115 例复发性缓解型 MS 患者，76 例分配至 PTA 组（45 例女性[59%]；平均[标准差]年龄，40.0[10.3]岁），39 例分配至假组（29 例女性[74%]；平均[标准差]年龄，37.5[10.6]岁）；112 例（97.4%）完成随访。未发生严重不良事件。PTA 组中 71 例患者中有 38 例（54%）实现了血流恢复。PTA 组和假组的功能综合测量无差异（41.7%对 48.7%；优势比，0.75；95%置信区间，0.34-1.68；P=0.49）。6 至 12 个月时磁共振成像上的平均（标准差）联合病变数量为 PTA 组 0.47（1.19），假组 1.27（2.65）（平均比，0.37；95%置信区间，0.15-0.91；P=0.03；调整后 P=0.09），0 至 12 个月时 PTA 组为 1.40（4.21），假组为 1.95（3.73）（平均比，0.72；95%置信区间，0.32-1.63；P=0.45；调整后 P=0.45）。6 至 12 个月随访时，PTA 组 70 例患者中有 58 例（83%）和假组 33 例患者中有 22 例（67%）磁共振成像上无新发病变（优势比，2.64；95%置信区间，1.11-6.28；P=0.03；调整后 P=0.09）。0 至 12 个月时，PTA 组 73 例患者中有 46 例（63.0%）和假组 37 例患者中有 18 例（49%）磁共振成像上无新发病变（优势比，1.80；95%置信区间，0.81-4.01；P=0.15；调整后 P=0.30）。
静脉 PTA 已被证明是一种安全但效果不大的技术；不能推荐该治疗方法用于 MS 患者。
clinicaltrials.gov 标识符：NCT01371760。
