RT Journal Article
SR Electronic
T1 Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 1319
OP 1324
DO 10.1136/jnnp-2021-326164
VO 92
IS 12
A1 Chenyu Wang
A1 Joshua Barton
A1 Kain Kyle
A1 Linda Ly
A1 Yael Barnett
A1 Hans-Peter Hartung
A1 Stephen W Reddel
A1 Heidi Beadnall
A1 Marinda Taha
A1 Alexander Klistorner
A1 Michael Harry Barnett
YR 2021
UL http://jnnp.bmj.com/content/92/12/1319.abstract
AB Objective To investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.Methods We monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.Results In patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.Conclusion We found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.All data relevant to the study are included in the article or uploaded as supplemental information.