Blood pressure (BP) management is essential in secondary stroke prevention. Strategies to ensure continuous home BP monitoring are needed. Few studies investigated factors influencing adherence to home BP management. Therefore, we designed a pilot study to investigate the feasibility of keeping BP diaries (BPDs) with personal images. In this prospective trial, we randomized persons with a diagnosis of stroke or transient ischemic attack into two groups: (i) 10 patients received a personalized BPD with pictures of their choosing and (ii) 10 patients received a BPD without photographs. We instructed participants in both groups to document their BP at home twice daily over 28 days. Adherence was defined as the number of BP measurements performed relative to the maximum number of recommended measurements. We assessed patient reported outcomes as exploratory endpoints. We found no statistically significant difference in mean adherence between the control group (64

Objective Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting 2.9 million people worldwide, often leading to permanent disability. MS patients frequently use eHealth tools due to their relatively young age. The Floodlight ® MS app is a scientifically designed smartphone application that helps patients monitor hand motor skills, walking ability and cognition between medical appointments. This study assesses the cost-effectiveness of using the Floodlight ® MS app alongside standard-of-care (SoC) versus SoC alone in patients with relapsing-remitting MS (RRMS) from the perspective of the healthcare system. Methods A 10-year decision-analytic model was developed to assess the cost-effectiveness of incorporating the Floodlight ® MS app alongside SoC. The analysis included treatment-naive individuals and those already on drug therapy, modelling the app's role in early detection of disease progression and relapses to improve quality-of-life. Results For treatment-naive patients, using the Floodlight ® MS app resulted in a 2,660 € increase in total costs but yielded potential medical-cost savings of 786 € through health improvements. These patients experienced fewer relapses and slower disability progression, translating to a quality-of-life improvement of 4.5 months in perfect health and an incremental-cost-effectiveness-ratio (ICER) of 7,071 €. Pre-treated patients showed similar trends, with medical-cost savings of 718 €, an ICER of 7,864 €, and a quality-of-life improvement of 4.2 months. Higher effectiveness (+5%) led to an additional 8.3 months in perfect health and a reduction in overall costs. Conclusion The analysis demonstrates that the Floodlight ® MS app is a cost-effective digital health application, encouraging broader discussions on maximizing the potential of software-as-medical-devices within the care pathway.

AbstractObjectiveTo investigate retinal layer thinning as a biomarker of disease‐modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).MethodsFrom an ongoing prospective observational study, we included patients with RMS, who (i) had an optical coherence tomography (OCT) scan within 6 to 12 months after DMT start (rebaseline) and ≥1 follow‐up OCT ≥12 months after rebaseline and (ii) adhered to DMT during follow‐up. Differences between DMT in thinning of peripapillary‐retinal‐nerve‐fiber‐layer (pRNFL) and macular ganglion cell‐plus‐inner plexiform‐layer (GCIPL) were analyzed using mixed‐effects linear regression. Eyes suffering optic neuritis during follow‐up were excluded.ResultsWe included 291 RMS patients (mean age 30.8 years [SD 7.9], 72.9% female, median disease duration 9 months [range 6–94], median rebaseline‐to‐last‐follow‐up‐interval 32 months [12–82]).Mean annualized rates of retinal layer thinning (%/year) in reference to DMF (n = 84, GCIPL 0.28, pRNFL 0.53) were similar under TERI (n = 18, GCIPL 0.34, pRNFL 0.59), GLAT (n = 24, GCIPL 0.32, pRNFL 0.56), and IFNb (n = 13, GCIPL 0.33, pRNFL 0.60) were slightly lower under S1PM (n = 27, GCIPL 0.19, pRNFL 0.42) and CLA (n = 23, GCIPL 0.20, pRNFL 0.42), and were significantly lower under NTZ (n = 47, GCIPL 0.09, pRNFL 0.24; both p < 0.001) and antiCD20 (n = 55, GCIPL 0.10, pRNFL 0.23; both p < 0.001). In patients achieving NEDA‐2, observed thinning rates were lower overall, but still significantly lower under NTZ and antiCD20.InterpretationApplying a rebaselining concept, retinal layer thinning differentiates DMT effects even in clinically stable patients and, thus, might be a useful biomarker to monitor DMT efficacy on subclinical neuroaxonal degeneration—at least on a group level.

BACKGROUND AND PURPOSE:The rapidly evolving landscape of effective treatment options in multiple sclerosis has led to a shift of treatment objectives towards a treat-to-target approach aiming to suppress disease activity below the level of detectability early during the disease. To enable treat-to-target, a thorough reappraisal of available outcome measures with respect to their ability in this regard is required. METHODS:To that end, we conducted a comprehensive systematic literature review of more than 1000 studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 methodology focusing on underlying evidence as well as utility and implementability in clinical practice. RESULTS:From there, we propose a set of measurable outcomes for everyday routine clinical practice as well as advanced/aspirational measurables requiring additional resources. We also outline remaining knowledge/technology gaps that need to be overcome to enable a treat-to-target approach. CONCLUSIONS:This work provides the basis for an evidence-based definition of outcome targets for relevant stakeholders and regulatory authorities.

BackgroundRecent studies proposed cellular immunoprofiling as a surrogate for predicting treatment response and/or stratifying the occurrence of adverse events (AEs) in persons with multiple sclerosis (pwMS). However, applicability in real-world circumstances is not sufficiently addressed.ObjectiveWe aimed to explore whether standard routine clinical leukocyte phenotyping before treatment initiation could help stratify patients according to treatment response or AEs in a real-world MS cohort.MethodsIn this retrospective study, 150 pwMS were included, who had been newly initiated on a disease-modifying drug (DMD) and had been assessed for standard immunophenotyping before DMD initiation (baseline) and at least once during the following year. Multivariate models were used to assess an association of immune subsets and the association between immune cell profiles regarding treatment response and AEs.ResultsWe found that the composition of T cell subsets was associated with relapse activity, as an increased proportion of CD8+ lymphocytes at baseline indicated a higher likelihood of subsequent relapse (about 9% per 1% increase in CD8+ proportion of all CD3+ cells). This was particularly driven by patients receiving anti-CD20 therapy, where also EDSS worsening was associated with a higher number of CD8+ cells at baseline (3% increase per 10 cells). In the overall cohort, an increase in the proportion of NK cells was associated with a higher risk of EDSS worsening (5% per 1% increase). Occurrence of AEs was associated with a higher percentage of T cells and a lower number of percentual NKT cells at baseline.ConclusionImmune cell profiles are associated with treatment response and the occurrence of AEs in pwMS. Hence, immunophenotyping may serve as a valuable biomarker to enable individually tailored treatment strategies in pwMS.

Background and ObjectivesIsolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome.MethodsCombining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for >= 12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for >= 2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses.ResultsA total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given >= 3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with >= 3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%.DiscussionIn our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred.Classification of EvidenceThis study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with >= 3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

Background: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). Methods: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6–12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFL baseline /aLpRNFL rebaseline ) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPL baseline /aLGCIPL rebaseline ) by mixed-effects linear regression models. Results: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFL baseline and aLGCIPL baseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFL rebaseline nor aLGCIPL rebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFL rebaseline (by 0.31%, p < 0.001) and aLGCIPL rebaseline (0.25%, p < 0.001) compared with M-DMT. Conclusions: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.

Zusammenfassung Digitalisierung in der Medizin gehört zur Zukunft der akademischen Medizin. Diesem Fakt wird auch in der Lehre Rechnung getragen. Da Lehre immer forschungsgeleitet gestaltet ist, sind auch die lerntheoretischen Grundlagen und Konzepte zu diskutieren. Die Implementierung digitaler Medizin stellt eine Möglichkeit als Brückenfunktion für eine gute interprofessionelle Zusammenarbeit dar. Diese Interprofessionalität erachten wir in unserem Fachgebiet als zentral, ebenso wie gutes Netzwerkmanagement. Die hier vorgestellten Anwendungen und deren Vermittlung im Unterricht führen in der interprofessionellen Arbeit zu einer Thematisierung von Denk- und Reflexionsprozessen, die eine bessere Arbeitszufriedenheit und Patient:innenzufriedenheit nach sich ziehen.

OBJECTIVE:In light of clinical trials and disease-modifying therapies, an early identification of patients at-risk of developing Alzheimer's disease (AD) is crucial. Blood-based biomarkers have shown promising results regarding the in vivo detection of the earliest neuropathological changes in AD. Herein, we investigated the ability of plasma p-tau181 to act as a prescreening marker for amyloid positivity in a heterogeneous memory clinic-based cohort. METHODS:In this retrospective cross-sectional study, we included a total of 115 patients along the clinical AD continuum (mild cognitive impairment [MCI] due to AD, n = 62, probable AD dementia, n = 53). Based on their biomarker status, they were stratified into an amyloid-positive (Aβ+, n = 88) or amyloid-negative cohort (Aβ-, n = 27). Plasma and CSF p-tau181 concentrations were quantified using an ultrasensitive single-molecule array (SIMOA©). Furthermore, age- and sex-adjusted receiver operating characteristic (ROC) curves were calculated and the area under the curve (AUC) of each model was compared using DeLong's test for correlated AUC curves. RESULTS:The median (interquartile range [IQR]) concentration of plasma p-tau181 was significantly higher in Aβ+ patients (3.6 pg/mL [2.5-4.6]), compared with Aβ- patients (1.7 pg/mL [1.2-1.9], p < 0.001). Regarding the distinction between Aβ+ and Aβ- patients and the prediction of amyloid positivity, a high diagnostic accuracy for plasma p-tau181 with an AUC of 0.89 (95% CI = 0.82-0.95) was calculated. Adding the risk factors, age and APOE4, to the model did not significantly improve its performance. INTERPRETATION:Our findings demonstrate that plasma p-tau181 could be a noninvasive and feasible prescreening marker for amyloid positivity in a heterogeneous clinical AD cohort and therefore help in identifying those who would benefit from more invasive assessment of amyloid pathology.

Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa (c) technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study - Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall's-Tau [tau] = 0.25, p = 0.01), and, interestingly with serum creatinine (tau = 0.28, p = 0.005) and estimated glomerular filtration rate (eGFR, tau =-0.28, p = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation.

Digitalisierung in der Medizin gehört zur Zukunft der akademischen Medizin. Diesem Fakt wird auch in der Lehre Rechnung getragen. Da Lehre immer forschungsgeleitet gestaltet ist, sind auch die lerntheoretischen Grundlagen und Konzepte zu diskutieren. Die Implementierung digitaler Medizin stellt eine Möglichkeit als Brückenfunktion für eine gute interprofessionelle Zusammenarbeit dar. Diese Interprofessionalität erachten wir in unserem Fachgebiet als zentral, ebenso wie gutes Netzwerkmanagement. Die hier vorgestellten Anwendungen und deren Vermittlung im Unterricht führen in der interprofessionellen Arbeit zu einer Thematisierung von Denk- und Reflexionsprozessen, die eine bessere Arbeitszufriedenheit und Patient:innenzufriedenheit nach sich ziehen.

BACKGROUND:Inter-individual courses of multiple sclerosis (MS) are extremely variable. The objective of this study was to investigate whether κ-free light chain (κ-FLC) index and serum neurofilament light (sNfL) have an additive predictive value for MS disease activity.METHODS:Patients with early MS who had cerebrospinal fluid (CSF) and serum sampling at disease onset were followed for four years. At baseline, age, sex, disease duration, number of T2-hyperintense (T2L), and contrast-enhancing T1 lesions (CEL) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying treatment (DMT) were registered. κ-FLC was measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient. sNfL was determined by single-molecule array, and age- and body-mass-index adjusted Z scores were calculated.FINDINGS:A total of 86 patients at a mean age of 33 ± 10 years and with a female predominance of 67% were included; 36 (42%) patients experienced a second clinical attack during follow-up. Cox regression analysis adjusted for age, sex, T2L, CEL, disease and follow-up duration, and DMT use during follow-up revealed that both κ-FLC index as well as sNfL Z score independently predict time to second clinical attack. The chance for freedom of relapse within 12 months was 2% in patients with high levels of κ-FLC index (>100) and high sNfL Z score (>3), 30% in patients with high κ-FLC index (>100) and lower sNfL Z score (≤3), 70% in patients with lower κ-FLC index (≤100) but high sNfL Z score (>3), and 90% in patients with lower levels of κ-FLC index (≤100) and sNfL Z score (≤3).INTERPRETATION:κ-FLC index and sNfL Z score have an additive predictive value for early MS disease activity that is independent of known predictors.FUNDING:This study was funded by a grant of the charitable foundation of the Austrian Multiple Sclerosis Society.

BACKGROUND: Critical illness polyneuropathy (CIP) commonly occurs in critical care unit (CCU) patients, but timely diagnosis can be challenging. Therefore, new biomarkers, such as serum neurofilament light chain (sNfL), could help to improve early identification of patients with this condition.METHODS: CIP was diagnosed or excluded with neurological assessment and nerve conduction measurement in a prospective study of CCU patients. sNfL and secondary predictors for neuropathy (neuron-specific enolase (NSE), S100, folic acid, and vitamin B12) were measured at admission. Cases and controls were compared regarding the predictors.RESULTS: Nineteen patients met the inclusion criteria. CIP was considered definitely or most likely present in seven (37%, cases) and definitely or most likely absent in 12 individuals (63%, controls). At admission, sNfL levels were sig-nificantly higher in the cases than in the controls: 405 (IQR 77 to 835) vs. 27 (IQR 12 to 90) pg/mL; difference of medians 375, 95% confidence interval [14, 736], pg/mL; P=0.04. We found no significant differences regarding the secondary predictors at baseline. Cases had longer durations of CCU stay (median 19 (IQR 11 to 44) vs. 8 (IQR five to ten) and increased mortality (57% vs. 33% deceased) compared to controls.CONCLUSIONS: Levels of serum neurofilament light chain are higher in patients who develop CIP soon after CCU admission and might be helpful in identifying those individuals early.

Introduction With the approval of natalizumab in Europe in 2006, the Austrian Multiple Sclerosis Therapy Registry (AMSTR) was established. Here, we present data from this registry about effectiveness and safety of natalizumab in patients treated up to 14 years. Patients/methods Data retrieved from the AMSTR contained baseline characteristics and biannual documentation of annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score as well as adverse events and reasons for discontinuation on follow-up visits. Results A total of 1596 natalizumab patients (71% women, n = 1133) were included in the analysis and the observed treatment duration ranged from 0 to 164 months (13.6 years). The mean ARR was 2.0 (SD = 1.13) at baseline, decreasing to 0.16 after 1 year and 0.01 after 10 years. A total of 325 patients (21.6%) converted to secondary progressive multiple sclerosis (SPMS) during the observational period. Of 1502 patients, 1297 (86.4%) reported no adverse events (AE) during follow-up visits. The most common reported AEs were infections and infusion-related reactions. John Cunningham virus (JCV) seropositivity was the most common specified reason for treatment discontinuation (53.7%, n = 607). There were five confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) with 1 death. Conclusion The effectiveness of natalizumab in patients with active relapsing–remitting multiple sclerosis (RRMS) could be confirmed in our real-world cohort even after follow-up of up to 14 years, though after year 10, there were less than 100 remaining patients. A low number of AE were reported in this nationwide registry study, establishing Natalizumab’s favourable safety profile during long-term use.

BACKGROUND AND OBJECTIVES:The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria. METHODS:From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral domain OCT scan obtained within 180 days. Modified DIS criteria (DIS + OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT intereye differences. Time to second clinical attack was the primary endpoint. RESULTS:We analyzed 267 patients with MS (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13-98). Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS + OCT 81.2% vs DIS 65.6%) and sensitivity (DIS + OCT 84.2% vs DIS 77.9%) without lowering specificity (DIS + OCT 52.2% vs DIS 52.2%). Fulfilling DIS + OCT criteria (≥2 of 5 DIS + OCT regions involved) indicated a similar risk of a second clinical attack (hazard ratio [HR] 3.6, CI 1.4-14.5) compared with a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2-11.8). When the analysis was conducted according to topography of the first demyelinating event, DIS + OCT criteria performed similarly in both optic neuritis and nonoptic neuritis. DISCUSSION:Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that adding the optic nerve as determined by OCT as a fifth DIS criterion to the 2017 McDonald criteria improves diagnostic accuracy.

BACKGROUND AND PURPOSE:This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS).METHODS:From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral-domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models.RESULTS:We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12-93). Mean pRNFL thickness was 92.6 μm (SD = 12.1), and mean GCIPL thickness was 81.4 μm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9-92). EDSS ≥ 3 was predicted with GCIPL < 77 μm (HR = 2.7, 95% CI = 1.6-4.2, p < 0.001) and pRNFL thickness ≤ 88 μm (HR = 2.0, 95% CI = 1.4-3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease-modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated.CONCLUSIONS:Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers.