AIM: Chronic fatigue (CF) severely affects patients with multiple sclerosis 
(MS), but its pathogenesis remains elusive and the effectiveness of available 
treatments is modest. We aimed to evaluate the effect on CF of the balloon 
dilatation of stenosing lesions affecting the main extracranial veins 
configuring the chronic cerebrospinal venous insufficiency (CCSVI), a condition 
strongly associated with MS.
METHODS: Thirty-one MS consecutive patients (16 males, age 46.2+/-9.4 years) 
with associated CCSVI and CF underwent the endovascular procedure. Fatigue was 
assessed using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact 
Scale (MFIS) at baseline (T0) and one (T1), six (T6) and twelve (T12) months 
after the procedure. In ambulatory patients (N.=28), mobility was evaluated 
using the 6-min walking test at T0 and T1.
RESULTS: and MFIS scores significantly improved from preoperative values, and 
the positive trend was maintained at one year (FSS: T0=5.1+/-1.0 to 
T12=3.5+/-1.8, P<0.001; MFIS-total score: T0=34.9+/-14.8 to T12=22.5+/-13.7, 
P<0.001; MFIS-Physical subscale: T0=21.2+/-8.0 to T12=13.5+/-9.7 P<0.001; 
MFIS-Cognitive subscale: T0=9.2+/-9.5 to T12=6.0+/-6.3, P=0.03; 
MFIS-Psychosocial subscale: T0=4.5+/-2.1 to T12=2.5+/-2.1, P<0.001). Six-min 
walking distance (6MWD) at T1 improved significantly (332+/-190m to 378+/-200m, 
P=0.0002). In addition, an inverted correlation between 6MWD and MFIS-physical 
subscale variations was found in the subgroup of patients (N.=8) with no lower 
limb motor impairment (r=-0.74, P=0.035).
CONCLUSION: The reestablishment of cerebral venous return dramatically reduced 
CF perception in a group of MS patients with associated CCSVI, suggesting that 
CF is likely the symptom of CCSVI.