The increasing number of disease‐modifying treatments available for multiple sclerosis has broadened treatment options for patients, but also challenges clinicians to select the best therapy for each ...individual at the appropriate stage of the disease. Early prediction of treatment response still remains one of the main difficulties in the management of multiple sclerosis patients. The concept of ‘no evidence of disease activity’ (NEDA) has been proposed as a surrogate for treatment response based on the absence of relapses, disability progression and radiological activity. Although there are several apparently logical arguments for the NEDA approach, there are also some major concerns that have to be considered and that are not sufficiently addressed yet. Amongst others, each parameter's limitations are not eliminated solely by its use within a composite score, and the contribution of each parameter to NEDA is not well balanced, as the detection of, for example, a single new magnetic resonance imaging lesion is considered as significant as the occurrence of a severely disabling relapse. NEDA in its current form also neglects underlying pathophysiology of the disease, has not been shown to fulfil formal criteria of a surrogate marker and its prognostic value has not been sufficiently evidenced yet. From a clinical point of view, ‘evidence of disease activity’ seems the more relevant surrogate; however, its implications are even less clear than those of NEDA. Here, existing literature on NEDA is critically reviewed and improvements are discussed that value its potential use in clinical trials and, even more importantly, treatment decision making in daily routine.
Background and purpose
Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a ...cut‐off value of pRNFL thinning rates in relapsing–remitting MS (RRMS) to discriminate between stable and progressing patients.
Methods
In this 3‐year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut‐off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut‐off values were validated using a multivariate logistic regression model.
Results
Average aLpRNFL in progressing patients (2.4 μm, SD 2.1) was significantly higher compared to stable patients (0.5 μm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 μm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 μm was associated with a 15‐fold increased risk of clinically progressing MS (P < 0.001).
Conclusions
A cut‐off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut‐off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.
Summary
The rapid initiation of immunotherapy has a decisive impact on the course of the disease in patients with antibody-mediated encephalitis (AE). The importance of treating AE with antiseizure ...medication and antipsychotics is discussed controversially; however, standardized procedures should be ensured, especially for the initiation of treatment in severe disease. Recommendations and guidelines for further interventions in refractory courses are needed. In this review, we contrast the three mainstays of treatment options in patients with AE and attempt to highlight the importance of 1) antiseizure therapy, 2) antipsychotic therapy, and 3) immunotherapy/tumor resection from today’s perspective.
Background
Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MS
ped
) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD
ped
) in ...children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode.
Methods
Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls.
Results
Thirteen MOGAD
ped
(10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MS
ped
(14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGAD
ped
compared to MS
ped
(pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm,
p
< 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm
3
,
p
< 0.001). Neither other macular layers nor P100 latency differed. MOGAD
ped
developed global atrophy affecting all peripapillary segments, while MS
ped
displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGAD
ped
). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%,
p
= 0.016).
Conclusion
First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.
Background and purpose
People with multiple sclerosis (MS) have to face important decisions with regard to their medical treatment. The aim of this study was to evaluate whether a targeted cognitive ...training reduces framing effects and thus improves medical judgments.
Methods
This was a randomized, double‐blind, cross‐over study enrolling patients with relapsing‐remitting MS and healthy controls (HCs). Participants were randomly assigned to training order A (first week, numerical training; second week, control training) or B (reverse order). The primary endpoint was changed in a framing task score (framing effect). In the framing task, participants evaluated the success of fictive medications on a 7‐point scale. Medications were described in either positive or negative terms.
Results
A total of 37 patients and 73 HCs performed either training order A (n = 56) or B (n = 54). The framing effect decreased after the numerical training regardless of training order. No such decrease was found after the control training. Mean change in framing effect was −0.3 ± 0.8 after the numerical training and 0.03 ± 0.6 after the control training. This specific effect of training type was comparable between groups.
Conclusion
Judgments of medical information improve in both patients with relapsing‐remitting MS and HCs after a targeted numerical training. Thus, a specific cognitive intervention may help patients making informed decisions.
Abstract Background Multiple sclerosis (MS) is a chronic inflammatory neurological disease requiring disease-modifying treatment (DMT). To provide patients with the optimal individual therapeutic ...option, treatment recommendations should be based not only on individual disease course and DMT specific benefit-risk estimates, but also on patient's individual characteristics such as personality, risk attitude and coping strategies. However, these characteristics are difficult to objectify in clinical routine practice without the support of appropriate evaluation instruments. Objective To identify and to assemble an objective test battery measuring personality, risk attitude and coping strategies in MS patients. Methods A comprehensive literature search was performed to obtain all questionnaires assessing personality, risk attitude and coping strategies. Availability in German language, validation in a published normative collective and a reliability of > 0.70 were required for our purposes. Based on these criteria, we chose the Big-Five-Personality Test, UPPS Impulsive Behaviour Scale, Domain-Specific Risk-Taking scale (DOSPERT), Brief-COPE and Stress & Coping Inventory (SCI). Results were compared to published normative controls of the respective questionnaires. Results Out of 22 MS patients (7 males, 15 females) participating in this study, 19 (86.4%) completed all questionnaires. The median completion time was 45 min (min–max range: 25–60 min). The median scores of the MS group were within the average range of published control samples in all questionnaires. Conclusions We report that traits of personality, risk attitude and coping strategies can be effectively and feasibly tested in MS patients by the instruments used in our exploratory study. There were no differences between MS patients and healthy controls, thus enabling assessment without being influenced by the diagnosis of MS. After validation in a larger cohort the “PeRiCoMS”-battery will be useful as another step towards a more individualized shared-decision-making in every day routine practice.
Background and purpose
Little is known about the natural history of non‐traumatic compressive mononeuropathies. To improve patient management, prognostic factors and outcome in patients with ...non‐traumatic peroneal and radial mononeuropathies were studied.
Methods
Retrospective clinical, electrophysiological and sonographic data of patients with non‐traumatic peroneal and radial mononeuropathies were evaluated. Clinical, electrophysiological and sonographic evaluations had to take place 2–12 weeks after symptom onset and follow‐up had to be for >6 months.
Results
Twenty‐five patients with peroneal mononeuropathy and 58 with radial mononeuropathy were included. Mean follow‐up was 8.9 ± 2.4 months. Approximately 90% of patients recovered to a muscle strength of British Medical Research Council grade 4 or 5. Multiple logistic regression analysis revealed conduction block on nerve conduction studies, younger age and less severe initial weakness as indicators for a good prognosis. Peripheral nerve ultrasound was not prognostic in the 40 patients where it was available.
Conclusions
The present study shows a good prognosis for spontaneous recovery after non‐traumatic acute‐onset compressive peroneal and radial mononeuropathies. Patients with denervation on needle electromyography, older age and severe initial weakness have a poorer prognosis and should be closely monitored to facilitate timely surgery whenever weakness persists. Peripheral nerve ultrasound seems to be of limited prognostic value in these mononeuropathies.
Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in several neurologic conditions. With increasing availability of fourth-generation immunoassays detecting NfL in ...blood, aspects of pre-analytical stability of this biomarker remain unanswered. This study investigated NfL concentrations in serum and plasma samples of 32 patients with neurological diagnoses using state of the art Simoa technology. We tested the effect of delayed freezing of up to 7 days and statistically determined stability and validity of measured concentrations. We found concentrations of NfL in serum and plasma to remain stable at room temperature when processing of samples is delayed up to 7 days (serum: mean absolute difference 0.9 pg/mL, intraindividual variation 1.2%; plasma: mean absolute difference 0.5 pg/mL, intraindividual variation 1.3%). Consistency of these results was nearly perfect for serum and excellent for plasma (intraclass correlation coefficients 0.99 and 0.94, respectively). In conclusion, the soluble serum and plasma NfL concentration remains stable when unprocessed blood samples are stored up to 7 days at room temperature. This information is essential for ensuring reliable study protocols, for example, when shipment of fresh samples is needed.
Background and Purpose
The coronavirus disease 2019 (COVID‐19) pandemic challenges neurologists in counseling multiple sclerosis (MS) patients with respect to their risk for and by severe acute ...respiratory syndrome coronavirus 2 and in guiding disease‐modifying treatment (DMT). The objective was to determine the frequency and distribution of currently known risk factors for COVID‐19 mortality in an MS population.
Methods
Multiple sclerosis patients with at least one complete case report between January 1, 2015 and December 31, 2019 from the Innsbruck MS database were cross‐sectionally included. Frequencies of currently estimated COVID‐19 mortality risk factors were analyzed, and the cumulative risk was calculated by a recently developed score. For every risk group, the proportions of patients under DMT and immunosuppressive treatment were determined.
Results
Of 1931 MS patients, 63.4% had low risk of COVID‐19 mortality, 26% had mild risk, 8.8% had a moderate risk, whereas a combined 0.9% had high or very high risk of COVID‐19 mortality. Of the patients at high or very high risk, only one patient received DMT and none had an immunosuppressive therapy.
Conclusions
In a population‐based MS cohort, the proportion of patients at high risk of COVID‐19 mortality is below 1%. Importantly, the vast majority of these MS patients did not receive any DMT.
The coronavirus disease 2019 (COVID‐19) pandemic challenges neurologists in counseling multiple sclerosis (MS) patients with respect to their risk by severe acute respiratory syndrome coronavirus 2 and in guiding disease‐modifying treatment (DMT). Risk of COVID‐19 mortality and the respective proportions of patients under DMT and immunosuppressive treatment according to mortality risk were analyzed in a population‐based cohort of 1931 MS patients. Only 0.8% of MS patients displayed a high risk of COVID‐19 mortality, with less than 1% of these patients receiving DMT or immunosuppressive therapy.
Retinal layer thickness parameters measured by optical coherence tomography (OCT) are emerging biomarkers of neuroaxonal degeneration and inflammation in multiple sclerosis (MS). We aimed to evaluate ...the value of retinal layer thickness for prediction of disability worsening and relapse in a real-world MS cohort.
For this longitudinal observational study, we included MS patients with spectral-domain OCT scans available and ≥1 year of clinical follow-up. The value of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and inner nuclear layer (INL) thickness for prediction of disability worsening and relapse during the observation period was tested by multivariate models.
We analyzed 60 MS patients during a mean observation period of 2.9 years (SD 1.8). Lower baseline thickness of GCIPL (cut-off <77µm; HR 4.1, p=0.001) and pRNFL (cut-off ≤88µm; HR 3.1, p=0.019) were associated with an increased risk of disability worsening. Longitudinally, mean thinning rates were -0.8µm/year (SD 1.6) for GCIPL, -0.6µm/year (SD 3.5) for pRNFL. GCIPL thinning ≥1.0µm/year and pRNFL >1.5µm/year is associated with higher likelihood of disability worsening (HR 5.7, p=0.009 and HR 6.8, p=0.003, respectively). INL thickened in patients with relapse by a mean 0.9µm while thinning by 0.3µm in patients without relapse (p=0.04). In multivariate analyses, INL thickening was associated with an increased probability of relapse (OR 17.8, p=0.023).
Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.
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