Efficacy and Safety of Extracranial Vein Angioplasty in Multiple Sclerosis

Abstract

IMPORTANCE 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.OBJECTIVE 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. INTERVENTIONS Patients were randomly allocated (2:1) to either venous PTA or catheter venography without venous angioplasty (sham).MAIN OUTCOMES AND MEASURES 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. RESULTSOf 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).CONCLUSION AND RELEVANCE Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01371760

An overview of randomized controlled trials on endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis patients

“…Clinical characteristics of MS patients recruited to these trials is presented in ▶ Table 1. Patients from the Brave Dreams study differ from the patients recruited to the other studiesthey were younger, with a shorter duration of the disease and all of them presented with relapsing-remitting clinical course of MS (which is an early and less debilitating stage of the disease) [16]. On the contrary, patients recruited to other trials (the Pisa study did not provide all demographic data) were older, with longer duration of MS and heterogeneous clinical course of the disease.…”

“…Thus far, only 4 randomized controlled studies evaluating clinical efficacy of endovascular treatments for CCSVI in MS patients have been published [14][15][16][17]. All these studies were rather small and seem underpowered.…”

“…Taking into account this new analysis, it seems that we need more studies evaluating clinical efficacy of venous angioplasty in selected MS patients. Importantly, all aforementioned trials and also the open-label surveys have demonstrated that venous angioplasty in MS patients is a safe procedure and that serious adverse events associated with this treatment are rare [6,10,11,14,16,17,20,25,30,31]. Therefore, from ethical point of view, new trials performed in selected patients, considering low risk and possible clinical benefit, seem justifiable.…”

Chronic cerebrospinal venous insufficiency theory after the Brave Dreams study

“…However, the description of the endovascular technique used by this team suggests that the patients probably received suboptimal treatment, and the lack of improvement could be associated with unsuccessful angioplasties and not the fact that such a procedure was not clinically beneficial. This year the results of a multicentre Italian trial (the Brave Dreams study) were published [21]. This study was planned to involve at least 300 patients, but only 112 completed the study.…”

Utilisation des dispositifs nanotechnologiques dans les pathologies dégénératives cérébrales. Étude prospective sur 28 patients atteints de sclérose en plaques

“…Les effets bénéfiques des champs magnétiques de faible intensité sur l'équilibre du corps et sur la posture ont stimulé un intérêt au niveau de l'amélioration de la performance sportive et des protocoles de rééducation [13,14].…”