Natalizumab discontinuation is associated with a rebound of cognitive impairment in multiple sclerosis patients

Natalizumab discontinuation is associated with a disease reactivation in multiple sclerosis (MS) patients. Whether this reactivation involves also cognitive functions is not known to date. To assess the persistence of the effect of natalizumab on cognitive functions 1 year after its discontinuation, we compared the longitudinal changes of cognitive performances in two groups of patients. The interrupters, 30 MS patients, have stopped natalizumab due to PML concern, and the continuers, 28 MS patients, continued the treatment. The cognitive impairment index (CII) was used as main outcome measure. As expected, during the natalizumab treatment, we observed a significant reduction of the relapse rate and the number of gadolinium-enhancing lesions along with a reduction of the CII. After 1 year of discontinuation, the beneficial effect on cognitive functions was lost in the interrupters group, as the mean CII increased in comparison with the mean at the end of natalizumab treatment (12.2 ± 7.9 vs 9.3 ± 8.1, p < 0.0001). As opposite, in the continuers group, the CII further decreased after an additional year of treatment (8.4 ± 5.1 vs 9.8 ± 4.6, p = 0.007). A multivariate logistic regression model revealed as predictors of cognitive worsening male sex, disease duration, and the treatment discontinuation. The worsening of cognitive functions after natalizumab discontinuation goes in parallel with the clinical/radiological disease reactivation. Our data reinforce the hypothesis that, in the short-term, natalizumab exerts its positive impact on cognitive functions by means of its anti-inflammatory properties.