Multiple Sclerosis Journal

The history of multiple sclerosis (MS) is dominated by the discoveries of famous men. However, women would like to feel part of the story and to know that women have contributed to MS research.

To identify women who contributed to the history of discovery in MS.

This was a personal survey from my knowledge of previous work.

There were no women participants in the early stages of MS research. However, since 1950 there are many women who have contributed to MS research. In the 20th century, there were famous women who contributed to the scientific fields that form the basis of MS research. In the 21st century, more women participate in MS research but studies suggest that they are under-represented in positions of prominence.

Women have been part of the effort to understand MS, but are not well recognized.

Neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1) concentrations in cerebrospinal fluid (CSF) may have prognostic value in clinically isolated syndromes (CIS) and relapsing–remitting multiple sclerosis (RRMS).

To compare the prognostic value of CSF concentrations of NFL and CHI3L1 in newly diagnosed CIS and RRMS patients.

NFL and CHI3L1 were measured in CSF in 177 newly diagnosed patients with CIS or RRMS who were followed clinically for a mean of 5.7 years.

At baseline CSF concentrations of NFL correlated with CSF concentrations of CHI3L1, relapses in the previous year, time from last relapse, and the Expanded Disability Status Scale (EDSS) score. CSF concentrations of NFL and CHI3L1 were both associated with increased relapse risk during the first 2 years in univariate analyses, but only the CSF concentration of NFL was independently associated with relapse risk in a multivariable analysis. There was no relationship between CSF concentrations of NFL or CHI3L1 and risk of conversion to secondary progressive MS or development of disability.

CSF concentrations of NFL are associated with 2-year relapse risk but not with disease progression or clinical worsening in newly diagnosed CIS and RRMS patients. This may be due to confounding by the effect of disease-modifying therapies.

This study looked at observed crude prevalence/incidence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in Malaysia and identified any inter-ethnic differences for MS/NMOSD.

This was a nationwide tertiary hospital–based retrospective cross-sectional study using the capture–recapture method. It looked at the estimated crude prevalence of confirmed MS and NMOSD and annual incidence on 29 December 2017. Recapture of data was done between February and March 2018 on 1 March 2018. Public and referring private institutions were accessed.

The survey identified 767 MS and 545 NMOSD subjects, with crude prevalence rates of 2.73 per 100,000 (95% confidence interval (CI): 2.53; 2.92 per 100,000 population) and 1.94 per 100,000 (95% CI: 1.77; 2.10 per 100,000 population) with observed crude annual incidence of 0.55 (95% CI: 0.43; 0.58) for MS and 0.39 per 100,000 (95% CI: 0.35; 0.47) for NMOSD. The MS:NMOSD ratios were 1.4:1.0. The capture–recapture method revealed 913 MS (95% CI: 910; 915.9) and 580 (95% CI: 578.8; 581.2) NMOSD with prevalence per 100,000 of 3.26 (95% CI: 3.05; 3.47) and 2.07 (95% CI: 1.90; 2.24), respectively. In the MS group, 59.4% were Malay, 16.6% Chinese, 20.5% Indian, and 3.5% were from indigenous groups. In the NMOSD group, 47.3% were Malay, 46.9% Chinese, 3.5% Indian, and 2.3% were from other indigenous groups. The ratio of NMOSD to MS among the Chinese was 2:1, but the ratio of MS to NMOSD among the Malays was 1.8:1, and that in Indians was 8.3:1.

There is a modest increase in the prevalence of MS and NMOSD in Malaysia with inter-ethnic differences for MS/NMOSD.

Progression is the major driver of disability and cost in multiple sclerosis (MS). However, the search for treatments in progressive multiple sclerosis (PMS) has not mirrored the success in relapsing MS.

To assess changes in PMS trials over time.

PubMed, MEDLINE and Embase were searched to identify randomised, double-blind, placebo-controlled trials in PMS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used, study quality was assessed and trends were examined by regression.

Placebo groups of 43 studies published between 1988 and 2018 were included. The mean age at trial entry increased by 9.8 years per decade (95% confidence interval (CI): [2.7; 4.9]; p < 0.001). Mean baseline Expanded Disability Status Scale (EDSS) scores increased by 0.36 points (95% CI: [0.09; 0.62]; p = 0.009) and disease durations at baseline were prolonged by 1.8 years (95% CI: [0.7; 2.9]; p = 0.003) per decade. The trials became larger, specifically placebo groups increased by about 222 patients (95% CI: [36; 409]; p = 0.021) and 88 patients (95% CI: [12; 165]; p = 0.025) per decade for primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS), respectively. The proportion of patients on placebo experiencing disability progression within 24 months decreased by 7.6 percentage points (95% CI: [1.2; 14.1]; p = 0.022) per year.

Over three decades, PMS trial populations changed and are now older, with a longer disease duration and more disability, with lower on-trial progression rates.

Hand motor deficits contribute to multiple sclerosis (MS)-related disability. Action observation training (AOT) is promising to improve upper limb function in neurologic patients.

In this preliminary study, we investigated AOT effects on dominant-hand motor performance in MS patients with upper limb motor impairment and performed an explorative analysis of their anatomical and functional magnetic resonance imaging (MRI) substrates.

In total, 46 healthy controls (HC) and 41 MS patients with dominant-hand motor impairment were randomized to AOT (HC-AOT = 23; MS-AOT = 20; watching daily-life action videos and execution) or control-training (HC-Control = 23; MS-Control = 21; watching landscapes videos and execution). Behavioral, structural, and functional (at rest and during object manipulation) MRI scans were acquired before and after a 2-week training.

After training, MS groups improved in right upper limb functions, mainly in AOT group (p from 0.02 to 0.0001). All groups showed regional increased and decreased gray matter volume, with specific AOT effects in fronto-temporal areas in MS-AOT (p < 0.001), without white matter (WM) integrity modifications. Increased and reduced recruitments of the action observation matching system and its connections in MS-AOT were found (p < 0.001). Motor improvements were correlated with volumetric and functional MRI modifications (r from −0.78 to 0.77, p < 0.001).

The 10-day AOT promotes clinical improvements in MS patients through structural and functional modifications of the action observation matching system.

To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).

A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters.

Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively.

The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients.

Preference-based measures of health-related quality of life (HRQL) are used as primary or secondary endpoints in multiple sclerosis (MS) research.

The purpose of this paper was to evaluate the structural, convergent, and known-groups validity of the preference-based multiple sclerosis index (PBMSI) of HRQL in people with MS.

Participants were recruited from three MS clinics in Montreal. Structural validity was assessed using polychoric correlation coefficients and factor analysis. To assess convergent validity, hypotheses were formulated about the strength of correlations between the PBMSI and other HRQL measures. Known-groups validity was assessed against different measures of disability.

The average age of the sample was 46 and 77% were women. Factor analysis supported the structural validity of the PBMSI; the items collectively were measuring one underlying construct. The PBMSI showed convergent validity against generic measures of HRQL, and known-groups validity between persons with different levels of disability.

The results of this study support the construct validity of the PBMSI as an outcome measure of HRQL in MS. The PBMSI overcomes limitations observed with currently used HRQL measures in MS and may be used to contrast different interventions for people with MS.

One factor hindering the widespread use of cognitive testing for people with multiple sclerosis (pwMS) is the need for a tester to administer tests.

To undertake a proof of concept study assessing the feasibility of a fully automated speech recognition version of the Symbol Digit Modalities Test (auto-SDMT) in detecting abnormalities in processing speed in pwMS.

A sample of 50 pwMS and 32 matched healthy control (HC) subjects was tested with the auto-SDMT and the Brief International Cognitive Assessment for MS (BICAMS).

The percentages of MS participants impaired on the auto-SDMT and the traditional oral SDMT were 34% and 32%, respectively. Excellent convergent validity was found between the two tests (MS: r = −0.806, p < 0.001 and HC: r = −0.629, p < 0.001). The auto-SDMT had a similar sensitivity and specificity to the traditional oral SDMT in predicting overall impairment on the BICAMS.

The auto-SDMT is a sensitive measure for detecting processing speed deficits in pwMS. The test, the first entirely computer administrated oral response version of the SDMT, uses speech recognition technology, thereby eliminating the need for a human tester. Replication of the results is required in a larger representative sample of pwMS.

The evidence associating diet and risk of multiple sclerosis is inconclusive.

We investigated associations between dietary patterns and risk of a first clinical diagnosis of central nervous system demyelination, a common precursor to multiple sclerosis.

We used data from the 2003–2006 Ausimmune Study, a case–control study examining environmental risk factors for a first clinical diagnosis of central nervous system demyelination, with participants matched on age, sex and study region. Using data from a food frequency questionnaire, dietary patterns were identified using principal component analysis. Conditional logistic regression models (n = 698, 252 cases, 446 controls) were adjusted for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, race, education, body mass index and dietary misreporting.

We identified two major dietary patterns – healthy (high in poultry, fish, eggs, vegetables, legumes) and Western (high in meat, full-fat dairy; low in wholegrains, nuts, fresh fruit, low-fat dairy), explaining 9.3% and 7.5% of variability in diet, respectively. A one-standard deviation increase in the healthy pattern score was associated with a 25% reduced risk of a first clinical diagnosis of central nervous system demyelination (adjusted odds ratio 0.75; 95% confidence interval 0.60, 0.94; p = 0.011). There was no statistically significant association between the Western dietary pattern and risk of a first clinical diagnosis of central nervous system demyelination.

Following healthy eating guidelines may be beneficial for those at high risk of multiple sclerosis.

Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research.

To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner.

Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician. EDSS and tele-EDSS scores were compared.

Overall, 41 adults participated (mean (standard deviation (SD)) age: 47.0 years (11.6); median EDSS: 2 (range: 0–7)); 37 required no in-home assistance for the tele-EDSS evaluation (e.g. help positioning camera). Mean difference between EDSS and tele-EDSS was 0.34 (95% confidence interval (CI): 0.07–0.61). For 88% of evaluations, tele-EDSS and EDSS scores were within 1 point (similar to reported in-person inter-rater differences). Unweighted kappa for agreement within 0.5 point was 0.72. Correlation for individual functional systems (FS) ranged from modest (vision: 0.37) to high (bowel/bladder: 0.79). Overall correlation between EDSS and tele-EDSS was 0.89 (p < 0.0001); and 0.98 (p < 0.0001) at EDSS range: 4–7.

In this proof of principle study, disability evaluation in mild to moderate MS is feasible using telemedicine without an aide at the patient’s location.

Multiple Sclerosis Quality-of-Life Questionnaire-54 (MSQoL-54) is a disease-specific instrument for assessing health-related quality of life (HRQoL). Due to the number of items, the time taken to complete it is long. A shorter 29-item version, Multiple Sclerosis Quality-of-Life Questionnaire-29 (MSQoL-29) is yet to be evaluated in English.

To assess reliability and acceptability of English version of MSQoL-29.

Among 100 participants with MS who first completed both MSQoL-54 and MSQoL-29, 91 completed MSQoL-29 after 4–8 weeks. We looked for internal consistency (Cronbach’s alpha), acceptability, reliability (intraclass correlation coefficients (ICCs)) and agreement (Bland–Altman plots).

ICCs were strongly positive between MSQoL-54 and MSQoL-29 (Physical Health Composite (PHC) –ICC = 0.914, confidence interval (CI) = 0.872–0.942; Mental Health Composite (MHC) – ICC = 0.875, CI = 0.814–0.916) and between the two MSQoL-29 (PHC – ICC = 0.970, CI = 0.955–0.980; MHC – ICC = 0.937, CI = 0.904–0.958). On Bland–Altman plots, the MSQoL-29 scores of 95% of participants during two visits were within the limits of agreement (LOAs). Time taken to complete MSQoL-29 was 7.2 ± 2.9 minutes and MSQoL-54 was 19.79 ± 5.4 minutes (p = 0.0001).

MSQoL-29 has good test–retest reliability in English-speaking population and was quicker to complete.

Cognitive problems are difficult to identify in patients with multiple sclerosis (MS).

To investigate the clinical applicability of the patient-reported MS Neuropsychological Screening Questionnaire (MSNQ-P).

Cut-off scores were determined to differentiate between cognitively impaired (n = 90), mildly cognitively impaired (n = 115), and cognitively preserved (n = 147) MS patients using receiver operating characteristic analyses.

We could not define specific and sensitive cut-off scores. Higher scores (≥27) did indicate cognitive impairment. Among patients with a higher education, lower scores (<12) indicated intact cognition.

Certain scores can indicate intact or impaired cognitive function. Still, MSNQ-P scores should be interpreted with caution.

Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster.

We present five cases of chronic and treatment refractory warts associated with fingolimod therapy.

Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod.

Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended.