Baseline Cognitive Function of Patients with Relapsing Remitting Multiple Sclerosis Is Associated with Therapeutic Response to Natalizumab

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Daniel Golan, MD , Rapparport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Mark Gudesblatt, MD , South Shore Neurologic Associates, Patchogue, NY
Karl Wisseman, N/A , South Shore Neurologic Associates, Patchogue, NY
Myassar Zarif, MD , South Shore Neurologic Associates, Patchogue, NY
Barbara Bumstead, MS, ANCP, MSCN , South Shore Neurologic Associates, Patchogue, NY
Lori Fafard, RN, BSN, CNRN, MSCN, CCRP , South Shore Neurologic Associates, Patchogue, NY
Cynthia Sullivan, PhD , Nursing, State University of New York @ Stony Brook, Stony Brook, NY
Jeffrey Wilken, PhD , Washington Neuropsychology Research Group, Washington, DC
Jared Srinivasan, N/A , South Shore Neurologic Associates, Patchogue, NY
Karen Blitz, DO , South Shore Neurologic Associates, Patchogue, NY
Marijean Buhse, PhD, NP, RN, MSCN , Stony Brook University, Stony Brook, NY
Glen Doniger, PhD , NeuroTrax Corporation, Modiin, Israel


Cognitive function of patients with multiple sclerosis (PwMS) has been correlated with brain atrophy and neurodegeneration. We hypothesized that PwMS with better cognitive function and lower EDSS before treatment with natalizumab, would respond more, in accordance with the 'window of opportunity' paradigm.

Objectives: To explore whether the therapeutic response to natalizumab is modified by the baseline cognitive function or level of disability (EDSS). 


76 relapsing-remitting PwMS completed a standardized validated computerized cognitive assessment battery (NeuroTrax) with analysis of age-and education-adjusted individual cognitive domain scores and a global cognitive (average) summary score (GCS). Cognitive scores and EDSS were evaluated twice: at baseline and after a time interval of 9-27 months of treatment with natalizumab. Repeated measures ANOVA was used to estimate the effects of baseline EDSS and GCS on the changes in EDSS and GCS after treatment, while controlling for the inter-evaluation time.

Results: 76 PwMS were evaluated [female: 54 (71%); EDSS 3.5±2; education: 14.8±2.7 years; time between evaluations:16.8±4.6 months]. A significant interaction was found between baseline global cognitive score and change in EDSS after natalizumab infusions [F(1,71)=4.6, P=0.035]. EDSS and GCS changes after natalizumab were not significantly modified by baseline EDSS. Contrary to our hypothesis, patients with low baseline cognitive scores (GCS of at least 1SD below age- and education-adjusted average) showed greater improvement in EDSS after treatment compared with patients with better cognitive function at baseline. GCS scores were also improved after natalizumab [F(1,71)=6.3, P=0.02]. An improvement of at least 0.5SD in GCS was noted in 17% of the patients. 


Cognitive function in PwMS may improve after treatment with natalizumab. Cognitive dysfunction in PwMS may not necessarily imply irreversible brain damage, but may be also due to ongoing inflammation that is amenable to treatment. The window of opportunity for treatment should not be defined by baseline EDSS.