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PURPOSE To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. METHODS We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers. RESULTS Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05). CONCLUSION Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin. Mean MWF reflects average myelin content, while MWF standard deviation (SD) describes variation in myelin within regions. The myelin heterogeneity index (MHI = SD/mean MWF) is a composite metric of myelin content and myelin variability. We investigated how mean MWF, SD, and MHI compare in differentiating MS from controls and their associations with physical and cognitive disability.Myelin water imaging data were acquired from 91 MS participants and 31 healthy controls (HC). Segmented whole-brain NAWM and corpus callosum (CC) NAWM, mean MWF, SD, and MHI were compared between groups. Associations of mean MWF, SD, and MHI with Expanded Disability Status Scale and Symbol Digit Modalities Test were assessed.NAWM and CC MHI had the highest area under the curve: .78 (95% confidence interval [CI]: .69, .86) and .84 (95% CI: .76, .91), respectively, distinguishing MS from HC.Mean MWF, SD, and MHI provide complementary information when assessing regional and global NAWM abnormalities in MS and associations with clinical outcome measures. Examining all three metrics (mean MWF, SD, and MHI) enables a more detailed interpretation of results, depending on whether regions of interest include areas that are more heterogeneous, earlier in the demyelination process, or uniformly injured.

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability. Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability. Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration. Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%, p ⩽ 0.04) and RRMS (between 13% and 26%, p ⩽ 0.02), and ProgMS MHI was associated with EDSS ( r = 0.42–0.52) and 9HPT ( r = 0.45–0.52). Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.

BACKGROUND Patients with multiple sclerosis (MS) experience progressive thinning in optical coherence tomography (OCT) measures of neuroaxonal structure regardless of optic neuritis history. Few prospective studies have investigated the effects of disease-modifying therapies on neuroaxonal degeneration in the retina. Alemtuzumab is a monoclonal antibody shown to be superior to interferon β-1a in treating relapsing-remitting MS (RRMS). The purpose of this study was to assess the effects of alemtuzumab and first-line injectable treatments on OCT measures of neuroaxonal structure including peripapillary retinal nerve fiber layer (RNFL) thickness and combined ganglion cell-inner plexiform (GCIP) layer volume in RRMS patients followed up over 5 years. METHODS In this retrospective pilot study with prospectively collected double cohort data, spectral domain OCT measures of RNFL thickness and GCIP volume were compared between alemtuzumab-treated RRMS patients (N = 24) and RRMS patients treated with either interferon-β or glatiramer acetate (N = 21). RESULTS Over a median of 60 months (range 42-60 months), the alemtuzumab cohort demonstrated a change in the mean RNFL thickness (thinning from baseline) of -0.88 μm (95% confidence interval [CI] -2.63 to 0.86; P = 0.32) and mean GCIP volume of +0.013 mm (95% CI -0.006 to 0.032; P = 0.18). Over the same time period, the first-line therapy-treated cohort demonstrated greater degrees of RNFL thinning (mean change in RNFL thickness was -3.65 μm [95% CI -5.40 to -1.89; P = 0.0001]). There was also more prominent GCIP volume loss relative to baseline in the first-line therapy group (-0.052 mm [95% CI -0.070 to -0.034; P < 0.0001]). CONCLUSIONS Alemtuzumab-treated patients with RRMS demonstrated relative stability of OCT-measured neuroaxonal structure compared with RRMS patients treated with either interferon-β or glatiramer acetate over a 5-year period. These findings, along with previous demonstration of improved brain atrophy rates, suggest that alemtuzumab may offer long-term preservation of neuroaxonal structure in patients with RRMS.

Background and purpose Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS. Methods A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI). Results In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108). Conclusion Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS.

Key Points Question Is myelin damage in normal-appearing white matter associated with cognitive impairment in participants with multiple sclerosis (MS)? Findings In this cross-sectional study of 73 participants with MS and 22 age-, sex-, and education-matched healthy controls, significant associations were observed in participants with MS between a quantitative neuroimaging measure of myelin and performance on cognitive tests validated for MS. No significant associations were found between myelin measures and cognitive performance in controls. Meaning These findings suggest that myelin damage that is completely invisible on standard clinical images but can be measured using myelin water imaging is involved in MS-related cognitive impairment., This cross-sectional study uses myelin water imaging to examine participants with multiple sclerosis as well as controls to see whether advanced imaging can show myelin damage that does not appear on standard imaging., Importance Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. Objective To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS. Design, Setting, and Participants In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019. Exposures MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS. Main Outcomes and Measures The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest—the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum—were selected a priori according to their known involvement in MS-related cognitive impairment. Results For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = −0.490; 95% CI, −0.697 to −0.284; P

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associated disease. We describe a multi-ethnic population with MOG antibody seropositivity from the University of British Columbia MS/NMO clinic.Methods: AQP4-antibody seronegative patients presenting 2005–2016 with CNS inflammatory disease suspicious for NMOSD, as well as 20 MS controls, were retrospectively tested for MOG-IgG1 antibodies by live cell-based assay at Oxford Autoimmune Neurology Diagnostic Laboratory (UK) and by a commercial fixed cell-based assay at MitogenDx (Calgary, Canada). Additional MOG seropositive cases were identified through routine clinical interaction (2016–2018) using one of these laboratories. Clinical data was reviewed retrospectively.Results: Retrospective testing identified 21 MOG seropositives (14 by live assay only, 3 by fixed assay only and 4 by both) representing 14% of the “NMOSD suspects” cohort. One multiple sclerosis (MS) control serum was MOG seropositive. Twenty additional MOG positive cases were identified prospectively. Of 42 patients (27 female), median disease onset age was 29 years (range 3–62; 9 pediatric cases), 20 (47%) were non-Caucasian, and 3 (7%) had comorbid autoimmune disease. Most common onset phenotypes were optic neuritis (23, 55%; 8 bilateral) and myelitis (9, 21%; 6 longitudinally extensive) Three of the patients in our cohort experienced cortical encephalitis; two presented with seizures. Onset was moderate-severe in 64%, but 74% had good response to initial steroid therapy. Cumulative relapse probability for the MOG positive group at 1 year was 0.428 and at 4 years was 0.628. Most had abnormal brain imaging, including cortical encephalitis and poorly demarcated subcortical and infratentorial lesions. Few “classic MS” lesions were seen. Optic nerve lesions (frequently bilateral) were long and predominantly anterior, but 5 extended to the chiasm. Spinal cord lesions were long and short, with involvement of multiple spinal regions simultaneously, including the conus medullaris.Conclusions: Our MOG seropositive patients display phenotypes similar to previous descriptions, including cortical lesions with seizures and conus medullaris involvement. Many patients relapsed, predominantly in a different CNS location from onset. Serologic data from two different cell-based antibody assays highlight the discrepancies between live and fixed testing for MOG antibodies.

The visuomotor mental rotation (VMR) of a saccade requires a response to a region of space that is dissociated from a stimulus by a pre-specified angle, and work has shown a monotonic increase in reaction times as a function of increasing oblique angles of rotation. These results have been taken as evidence of a continuous process of rotation and have generated competing hypotheses. One hypothesis asserts that rotation is mediated via frontoparietal structures, whereas a second states that a continuous shift in the activity of direction-specific neurons in the superior colliculus (SC) supports rotation. Research to date, however, has not examined the neural mechanisms underlying VMR saccades and both hypotheses therefore remain untested. The present study measured the behavioural data and event-related brain potentials (ERP) of standard (i.e., 0° of rotation) and VMR saccades involving 35°, 70° and 105° of rotation. Behavioural results showed that participants adhered to task-based rotation demands and ERP findings showed that the amplitude of the contingent negative variation (CNV) linearly decreased with increasing angle of rotation. The cortical generators of the CNV are linked to frontoparietal structures supporting movement preparation. Although our ERP design does not allow us to exclude a possible role of the SC in the rotation of a VMR saccade, they do demonstrate that such actions are supported by a continuous and cortically based rotation process.

Tactile-based pantomime-grasping requires that a performer use their right hand to 'grasp' a target previously held in the palm of their opposite hand - a task examining how mechanoreceptive (i.e., tactile) feedback informs the motor system about an object property (i.e., size). Here, we contrasted pantomime-grasps performed with (H+) and without (H-) haptic feedback (i.e., thumb and forefinger position information derived from the grasping hand touching the object) with a condition providing visual KR (VKR) related to absolute target object size. Just-noticeable-difference (JND) scores were computed to determine whether responses adhered to - or violated - Weber's law. JNDs for H+ trials violated the law, whereas H- and VKR trials adhered to the law. Accordingly, results demonstrate that haptic feedback - and not KR - supports an absolute tactile-haptic calibration.

Relative visual information has been shown to mediate grasping responses directed to an area previously occupied by a target object (i.e., pantomime-grasping) and is an information type functionally distinct from the absolute visual information supporting naturalistic grasping (i.e., grasping a physical target). Pantomime- and naturalistic grasps differ not only in terms of their visual properties, but also because the former lacks physical interaction with a target object (i.e., no-haptic feedback). The absence of haptic feedback may represent a reason why pantomime- and naturalistic grasps differ. To address this issue, participants completed pantomime-grasps to objects embedded in fins-in and fins-out configurations of the Müller-Lyer (ML) illusion following a 2000-ms visual delay when haptic feedback was unavailable (H- condition), and when experimentally induced (H+ condition). In particular, in the H+ condition the experimenter placed a physical target object between participants' thumb and forefinger after they completed their grasping response. H- and H+ conditions were performed when online vision was available (i.e., Experiment 1) and when withdrawn (i.e., Experiment 2). If haptic feedback influences grasping, then the absolute information afforded from physically touching a target object (i.e., the H+ condition) should result in aperture metrics that are refractory-or attenuated-to the relative properties of the ML figures. Grip apertures in H- and H+ conditions were "tricked" in a direction consistent with the perceptual effects of the ML illusion; however, Experiment 2 showed that illusory effects were attenuated in the H+ condition. In other words, responses without online vision showed evidence of a visuo-haptic calibration. These results provide convergent evidence that haptic and visual feedback play a salient role in considering the extant literature's documented report of kinematic differences between pantomime- and naturalistic grasps.

Objective The objective of this study was to characterize the use of cannabis-based products (CBPs) by multiple sclerosis (MS) patients who attend the University of British Columbia Hospital (UBCH) MS clinic. Methods All patients attending the UBCH MS clinic from January to March 2018 were invited to participate in an anonymous survey that included: patient demographics (sex, age and employment status), self-reported MS-specific data (subtype, disease duration, previous and current disease modifying therapies, symptomatic medications) and CBP use (formulation, frequency, perceived benefits/side-effects). A second cohort of retrospective patient data (CBP use, sex, age, disease subtype and Expanded Disability Status Scale) was extracted from the UBCH MS clinic electronic medical record (EMR). Results Of 600 surveys distributed, 188 were returned with completed CBP usage. CBP use was daily for 19% (n = 37), weekly for 6% (n = 11), monthly for 4% (n = 7), rarely for 21% (n = 39) and 50% (n = 94) never used. Of the CBP users (daily, weekly and monthly), CBP use included: oral (n = 43/55), smoked/vaporized (n = 42/55), topical (n = 14/55) and mucosal (n = 5/55). EMR data was available for 561 MS patients where cannabis use/non-use was documented. CBP users represented 19% (107/561). Conclusions CBP use is common based on volunteer reporting, with approximately one out of four patients who attend the UBCH MS clinic using CBPs.

Background Progressive solitary sclerosis is a unifocal demyelinating disease recently proposed as a possible multiple sclerosis variant. Objective To compare myelin content and brain metabolite ratio qualitatively in the normal-appearing white matter of progressive solitary sclerosis cases compared to multiple sclerosis and healthy control participants. Methods Case report. Results Progressive solitary sclerosis cases showed abnormal myelin in normal-appearing white matter tracts and global normal-appearing white matter as well as lower N-acetyl-aspartate to total creatine ratio compared to multiple sclerosis and healthy control groups. Conclusion Despite a single demyelinating lesion along the corticospinal tract in progressive solitary sclerosis, we showed evidence of more extensive abnormality within the normal-appearing white matter.

We report a case of alopecia associated with alemtuzumab treatment for MS, the third case described in the literature, to our knowledge.1,2 A 31-year-old woman diagnosed with relapsing-remitting MS in February 2015 presented with demyelinating lesions in the medulla, cerebellar peduncle, cerebellar hemisphere in addition to >9 T2 supratentorial lesions on brain MRI. She was treated with an MS disease-modifying therapy (dimethyl fumarate 240 mg twice a day) for 8 months and experienced 2 clinical relapses during this time, prompting escalation to treatment with alemtuzumab (60 mg) in June 2016. Her second course of treatment with alemtuzumab (36 mg) occurred in June 2017, with lymphocyte count reaching 0.5 × 109/L 30 days posttreatment. Following alemtuzumab treatment, the patient was healthy without clinical or radiologic MS disease activity and had no other medical concerns. Two months after second course of treatment with alemtuzumab, the patient had a lymphocyte count of 0.7 × 109/L and experienced significant patchy hair loss, and a dermatologist confirmed the diagnosis of alopecia areata (AA). Hair loss continued over a period of 5 months, during which her lymphocyte count ranged from 0.7 to 0.8 × 109/L. She had a positive hair pull test, indicating further hair loss, despite treatment with intralesional scalp injections of triamcinolone acetonide (5 mg/cc, 3 cc total) in most of the affected areas both on AA diagnosis and 1 month later. Six months after the second course of alemtuzumab, the patient experienced a sensory partial transverse myelitis relapse, which was acutely managed with intravenous methylprednisolone 1,000 mg for 5 days. Within 4 weeks after her systemic steroid treatment, hair regrowth including regions of depigmentation was noted. The patient's lymphocyte count during this time was 0.9 × 109/L. Within 4 months of steroid treatment, hair regrowth was present over the entire scalp (figure). The authors thank Krista Barclay for her help in managing the patient.

Grasping a three-dimensional (3D) object results in the specification of motor output via absolute size information. In contrast, the impoverished visual cues (e.g., binocular and vergence) associated with grasping a two-dimensional (2D) object are reported to render aperture formation via an object's perceptual and relative visual features. It is, however, important to recognize that 3D and 2D grasping differ not only in terms of their visual properties, but also because the latter does not entail the provision of haptic feedback. As such, the present work examined whether haptic feedback influences the nature of the information supporting 2D grasping. Participants grasped differently sized 3D objects (i.e., 3D task) and completed a 'traditional' 2D grasping task to line drawings without receiving haptic feedback (i.e., 2DH- task). As well, we included a separate condition using the same objects as the 2DH- task; however, the experimenter placed a 3D object (i.e., one corresponding to the size of the 2D object) between the thumb and forefinger of participants' grasping limb once they completed their response (i.e., 2DH+ task). Thus, the 2DH+ task provided haptic feedback related to absolute object size. Notably, we computed just-noticeable-difference (JND) scores to determine whether the different tasks adhered to, or violated, the relative psychophysical principles of Weber's law. JNDs for the 2DH- task adhered to Weber's law, whereas 3D and 2DH+ tasks violated the law. Thus, results evince that 2DH- and 2DH+ tasks are specified via relative and absolute object size information, respectively. Accordingly, we propose that haptic feedback supports an absolute visuo-haptic calibration and contend that our results highlight the importance of multi-sensory cue integration in goal-directed grasping.