The three pillars in treating antibody-mediated encephalitis.

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.

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) 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 MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (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 MOGADped compared to MSped (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 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped 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 MOGADped). 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.

Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis.

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.

Improvement of medical judgments by numerical training in patients with multiple sclerosis.

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.

'No evidence of disease activity' - is it an appropriate surrogate in multiple sclerosis?

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.

Combined evaluation of personality, risk and coping in MS patients: A step towards individualized treatment choice - The PeRiCoMS-Study I.

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 45min (min-max range: 25-60min). 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.

Prognosis and prognostic factors in non-traumatic acute-onset compressive mononeuropathies--radial and peroneal mononeuropathies.

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.