Background NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far. Objective To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia. Methods We analyzed data for 334 patients, who received at least one infusion of NTZ. Relapse rate, MRI activity, NEDA-3 status after 2 years were assessed. Anti-JC virus antibodies status and RMP implementation were evaluated. Drop-out rate and reasons for therapy discontinuation were analyzed. Results Patients switched to natalizumab in Russia are mainly female (63%), with median EDSS score of 3.5 and high disease activity: 93% had at least 1 relapse and 58% had both T1Gd+ and new T2 lesion a year before therapy initiation. Introduction of federal reimbursement allowed patients with less relapses to start therapy with natalizumab. The only predictor of 6-month progression was EDSS score at the baseline of therapy (HR = 2.1375, 95%CI 1.0026–4.5570, p = 0.0492). 82% patients reached NEDA-3 at 24 month of therapy. 25% of patients discontinued NTZ for reasons: tolerability (14.5%), JCV antibody status (61%), and patient’s decision (17%). RMP was implemented in only 36% patients. Conclusion Natalizumab appeared to have high efficacy in Russian clinical practice. Federal reimbursement allowed less active patients to start natalizumab. More efforts should be done to improve RMP implementation.

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Aim: to explore the opportunities of application of diffusionkurtosis imaging (DKI) for assessment and estimation of diffusion scalar metrics in different locations of peritumoral edema for extra- and intracerebral tumors and in contralateral normal tissue.Materials and methods. 38 patients with supratentorial brain tumors were investigated: 24 (63%) patients with primarily revealed glioblastomas (GB) and 14 (37%) patients with solitary cancer brain metastasis (MTS). MRI was performed on 3.0 T MR-scanner (Signa HDxt, General Electric, USA) with the standard protocols for brain tumor and additional protocol for DKI. The standard protocol for brain tumor included: T1-, T2-weighted images, T2-FLAIR, DWI,  T1 with contrast enhancement. Diffusion kurtosis MRI based on SE  EPI with TR = 10000 ms, TE = 102 ms, FOV = 240 mm, isotropic voxel size 3 × 3 × 3 mm3, 60 noncoplanar diffusion directions. We  used three b-values: 0, 1000 and 2500 s/mm2. Аcquisition time was 22 min. Total acquisition time was near 40 min. This study was approved by Ethical committee of Burdenko National Scientific  and Practical Center for Neurosurgery. Parametric maps were  constructed for the following diffusion coefficients: mean (MK),  transverse / radial (RK), longitudinal / axial (AK) kurtozis; medium  (MD), transverse / radial (RD) and longitudinal / axial (AD) diffusion; fractional anisotropy (FA) and a bi-exponential diffusion model  coefficients: axonal water fractions (AWF), axial (AxEAD) and radial  (RadEAD) extra-axonal water diffusion and the water molecules  trajectory tortuosity index (TORT). Normative quantitative indicators  were obtained for the six regions of the peritumoral zone as they  moved away from the tumor (region 2) to the edema periphery  (regions 4–5), as well as in the normal brain on the contralateral  hemisphere (C/L) (zone 7). A comparative analysis of these  indicators was conducted for cases with GB and MTS. DKI scalar metrics were estimated using Explore DTI (http://www.exploredti.com/).Results. Anatomic MRI (T1 without/with contrast enhancement) for  all cases with GB and MTS visualized a contrast enhancement tumor.  The peritumoral edema, spreading mainly over the brain white  matter, was well visualized on T2-FLAIR. Diffusion kurtosis  coefficients decreased in the near peritumoral edema (regions 2–3)  and a gradually increased to the edema periphery (regions 5–6). In Region 2, MK in both GB and MTS groups were MKGB(2) = 0.637 ±  0.140 and MKMTS(2) = 0.550 ± 0.046; RK in this region were  RKGB(2) = 0.690 ± 0.154 and RKMTS (2) = 0.584 ± 0.051.  Differences both MK and RK coefficients in patients with GB and MTS of region 2 were significant (p < 0.001). There were no differences in AK values for GB and MTS in region 2 (p > 0.05), but in regions 3  and 4 differences were observed (p < 0.01). The minimum value of  AK in the central edema (regions 3–4) was AKMTS(3–4) = 0.433 ± 0.063 in patients with MTS. The values of MK and RK on the  contralateral side in patients with MTS were significantly higher than  in the GB group (p < 0.02); MKC/LMTC = 0.954 ± 0.140, RKC/LMTC  = 1.257 ± 0.308 and MKC/LGB = 0.829 ± 0.146, RKc/LGB = 0.989  ± 0.282. There was no significant difference for contralateral AK between the groups.Conclusions. We found that DKI scalar metrics are the sensitive  tumor biomarkers. It allows us to perform a robust differentiation  between the infiltrating GB tumor and purely vasogenic edema of  МТS. The obtained results will allow further differential diagnosis of  extra- and intracerebral tumors and can be used to plan surgical /  radiosurgical treatment for brain tumors.

The high percentage of withdrawal of treatment due to the lack of clinical effect and intolerance to the drugs was identified during the treatment. Positive effect with respect to stabilization of MS course was found only in patients who earlier did not receive disease-modifying drugs. Double-blind studies are needed to resolve the question of the adequacy of brand-name drugs and generics.

DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.