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The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials.

Supplemental material, MSJ865739_supplemental_material for Single-subject structural cortical networks in clinically isolated syndrome by Sara Collorone, Ferran Prados, Marloes HJ Hagens, Carmen Tur, Baris Kanber, Carole H Sudre, Carsten Lukas, Claudio Gasperini, Celia Oreja-Guevara, Micaela Andelova, Olga Ciccarelli, Mike P Wattjes, Sebastian Ourselin, Daniel R Altmann, Betty M Tijms, Frederik Barkhof and Ahmed T Toosy in Multiple Sclerosis Journal

Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy.

Supplemental material, MSJ885107_supplemental_material for Reduced neurite density in the brain and cervical spinal cord in relapsing–remitting multiple sclerosis: A NODDI study by Sara Collorone, Niamh Cawley, Francesco Grussu, Ferran Prados, Francesca Tona, Alberto Calvi, Baris Kanber, Torben Schneider, Lucas Kipp, Hui Zhang, Daniel C Alexander, Alan J Thompson, Ahmed Toosy, Claudia AM Gandini Wheeler-Kingshott and Olga Ciccarelli in Multiple Sclerosis Journal

Supplemental material, MSJ885107_supplemental_material for Reduced neurite density in the brain and cervical spinal cord in relapsing–remitting multiple sclerosis: A NODDI study by Sara Collorone, Niamh Cawley, Francesco Grussu, Ferran Prados, Francesca Tona, Alberto Calvi, Baris Kanber, Torben Schneider, Lucas Kipp, Hui Zhang, Daniel C Alexander, Alan J Thompson, Ahmed Toosy, Claudia AM Gandini Wheeler-Kingshott and Olga Ciccarelli in Multiple Sclerosis Journal