Extended interval dosing of natalizumab: a two-center, 7-year experience

Background: The enthusiasm for natalizumab, a highly efficacious agent in the treatment of multiple sclerosis (MS), has been tempered by the risks of progressive multifocal leukoencephalopathy associated with its use, and strategies to minimize those risks are of great interest. Extended interval dosing (EID) has been proposed as a way to maintain the efficacy of natalizumab while reducing exposure to it. We reviewed a cohort of patients who received natalizumab at 6–8-week intervals instead of the typical infusions every 4 weeks with the goal to assess if patients on EID had an increase in clinical relapses. Methods: This is a retrospective review of all patients with MS treated with natalizumab at two MS centers where patients were offered the opportunity to switch to an EID every 6 or 8 weeks. Results: A total of 361 patients received natalizumab for 22 ± 13 months (minimum duration 6 months). Of these, 96 patients received EID natalizumab at some point for 20 ± 11 months (minimum duration 6 months). Over the study period, there was no significant difference between the relapse rate in the monthly dosing (13%) and the EID (13%) groups of patients. Conclusion: Natalizumab is effective in controlling MS as very few clinical relapses were observed in our dataset. We found that EID did not compromise the treatment effect as measured by relapse rate and no significant breakthrough disease activity was observed. EID is an optional regimen for maintenance natalizumab therapy, but prospective studies are warranted to determine its efficacy

Untangling the R2* contrast in multiple sclerosis: A combined MRI-histology study at 7.0 Tesla.

T2*-weighted multi-echo gradient-echo magnetic resonance imaging and its reciprocal R2* are used in brain imaging due to their sensitivity to iron content. In patients with multiple sclerosis who display pathological alterations in iron and myelin contents, the use of R2* may offer a unique way to untangle mechanisms of disease. Coronal slices from 8 brains of deceased multiple sclerosis patients were imaged using a whole-body 7.0 Tesla MRI scanner. The scanning protocol included three-dimensional (3D) T2*-w multi-echo gradient-echo and 2D T2-w turbo spin echo (TSE) sequences. Histopathological analyses of myelin and iron content were done using Luxol fast blue and proteolipid myelin staining and 3,3'-diaminobenzidine tetrahydrochloride enhanced Turnbull blue staining. Quantification of R2*, myelin and iron intensity were obtained. Variations in R2* were found to be affected differently by myelin and iron content in different regions of multiple sclerosis brains. The data shall inform clinical investigators in addressing the role of T2*/R2* variations as a biomarker of tissue integrity in brains of MS patients, in vivo

Evaluating single-point quantitative magnetization transfer in the cervical spinal cord: Application to multiple sclerosis

Spinal cord (SC) damage is linked to clinical deficits in patients with multiple sclerosis (MS), however, conventional MRI methods are not specific to the underlying macromolecular tissue changes that may precede overt lesion detection. Single-point quantitative magnetization transfer (qMT) is a method that can provide high-resolution indices sensitive to underlying macromolecular composition in a clinically feasible scan time by reducing the number of MT-weighted acquisitions and utilizing a two-pool model constrained by empirically determined constants. As the single-point qMT method relies on a priori constraints, it has not been employed extensively in patients, where these constraints may vary, and thus, the biases inherent in this model have not been evaluated in a patient cohort. We, therefore, addressed the potential biases in the single point qMT model by acquiring qMT measurements in the cervical SC in patient and control cohorts and evaluated the differences between the control and patient-derived qMT constraints (kmf, T2fR1f, and T2m) for the single point model. We determined that the macromolecular to free pool size ratio (PSR) differences between the control and patient-derived constraints are not significant (p>0.149 in all cases). Additionally, the derived PSR for each cohort was compared, and we reported that the white matter PSR in healthy volunteers is significantly different from lesions (p<0.005) and normal appearing white matter (p<0.02) in all cases. The single point qMT method is thus a valuable method to quantitatively estimate white matter pathology in MS in a clinically feasible scan time. Keywords: Multiple sclerosis, Spinal cord, Normal appearing white matter, qMT, M

Summary of the findings.

<p>Summary of the findings.</p