PT  - JOURNAL ARTICLE
AU  - Chenyu Wang
AU  - Joshua Barton
AU  - Kain Kyle
AU  - Linda Ly
AU  - Yael Barnett
AU  - Hans-Peter Hartung
AU  - Stephen W Reddel
AU  - Heidi Beadnall
AU  - Marinda Taha
AU  - Alexander Klistorner
AU  - Michael Harry Barnett
TI  - Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy
AID  - 10.1136/jnnp-2021-326164
DP  - 2021 Dec 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 1319--1324
VI  - 92
IP  - 12
4099  - http://jnnp.bmj.com/content/92/12/1319.short
4100  - http://jnnp.bmj.com/content/92/12/1319.full
SO  - J Neurol Neurosurg Psychiatry2021 Dec 01; 92
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.