AlphaMissense prediction for the evaluation of missense variants in the diagnostic setting of neuromuscular disorders.

Next-generation sequencing has improved diagnostic outcomes for neuromuscular disorders, but interpreting rare missense variants remains challenging. We evaluated AlphaMissense, a recently developed machine learning tool, for predicting missense variant pathogenicity, using 45 (likely) pathogenic variants and 21 variants of uncertain significance from 58 deeply phenotyped patients. AlphaMissense predicted 69% of pathogenic variants correctly, but also classified 62% of variants of uncertain significance as pathogenic.

Serum neurofilament light chain and glial fibrillary acidic protein levels are associated with inner retinal layer thinning in multiple sclerosis.

Background: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) are emerging biomarkers of axonal damage and astrocytic activation. The value of sNfL and GFAP in predicting retinal layer thinning remains underexplored.

Objectives: To evaluate the association between sNfL and GFAP levels and retinal layer thinning.

The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple Sclerosis.

Objective: To investigate whether the rs10191329 risk allele in the DYSF-ZNF638 locus, which is implicated in central nervous system resilience rather than immune-mediated pathology, is associated with retinal layer thinning, a biomarker of neuroaxonal damage in relapsing multiple sclerosis (RMS).

Methods: From a prospective observational study, we included RMS patients with ≥ 2 optical coherence tomography (OCT) scans, excluding eyes with optic neuritis during the observation period. DNA samples were genotyped using the Illumina Infinium Global Screening Array-24 and variants imputed using the Haplotype Reference Consortium panel and Minimac4.

Signs of Intracranial Hypertension in Chronic Inflammatory Polyradiculoneuropathies-A Cross Sectional Cohort Study.

Introduction: Inflammatory polyradiculoneuropathy (IPN) has been associated with intracranial hypertension (IH) in various case reports, suggesting a potential link between the two conditions. However, the prevalence of IH in patients with IPN has not been addressed by prospective studies.

Methods: In this cross-sectional prospective study, we prospectively screened consecutive patients with chronic IPN for the presence of clinical and paraclinical signs of IH (fundoscopy, perimetry, optical coherence tomography, ultrasonography) between August 31, 2021, and December 31, 2023.

Diagnostic accuracy of inter-eye difference of ganglion cell layer alone in identifying optic neuritis in multiple sclerosis.

Introduction: The 2024 McDonald criteria for diagnosing multiple sclerosis (MS) include optic nerve involvement as a fifth region for establishing dissemination in space. Optic neuritis (ON) can be detected through optical coherence tomography (OCT) using an inter-eye absolute or percentage difference (IEAD, IEPD) in ganglion cell-inner plexiform layer (GCIPL) thickness.

Objective: To compare the diagnostic accuracy of GCIPL IEAD/IEPD with GCL and IPL IEAD/IEPD alone for identifying a history of ON.

Retinal thinning differentiates treatment effects in relapsing multiple sclerosis below the clinical threshold.

Objective: To investigate retinal layer thinning as a biomarker of disease-modifying treatment (DMT) effects in relapsing multiple sclerosis (RMS).

Methods: From 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.

The presence of oligoclonal bands predicts conversion to multiple sclerosis in isolated myelitis.

Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause).

Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity.

Background And Objectives: Isolated 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.

Methods: Combining 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 β, 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.

Immunophenotyping in routine clinical practice for predicting treatment response and adverse events in patients with MS.

Background: Recent 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.

Objective: We 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.

Next-generation sequencing and comprehensive data reassessment in 263 adult patients with neuromuscular disorders: insights into the gray zone of molecular diagnoses.

Background: Neuromuscular disorders (NMDs) are heterogeneous conditions with a considerable fraction attributed to monogenic defects. Despite the advancements in genomic medicine, many patients remain without a diagnosis. Here, we investigate whether a comprehensive reassessment strategy improves the diagnostic outcomes.

Lower serum cholesterol levels as a risk factor for critical illness polyneuropathy: a matched case-control study.

Critical illness polyneuropathy (CIP) is a frequent and underdiagnosed phenomenon among intensive care unit patients. The lipophilic nature of neuronal synapses may result in the association of low serum cholesterol levels with a higher rate of CIP development. We aimed to investigate this issue in critically ill patients.

Serum neurofilament light chain as an early diagnostic biomarker for critical illness polyneuropathy.

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.

Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for Multiple Sclerosis.

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.

Reported neurological symptoms after severe acute respiratory syndrome coronavirus type 2 infection: A systematic diagnostic approach.

Background And Purpose: Following increasing demands of patients with suspected neurological symptoms after infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the Department of Neurology at the Medical University of Vienna established a new outpatient clinic to systematically assess, diagnose, and document neurological complaints potentially associated with a prior SARS-CoV-2 infection.

Methods: The data presented here include prospectively collected 156 outpatients from May 2021 to April 2022. Patients underwent semistandardized interviewing about symptoms with reported onset after SARS-CoV-2 infection, neurological examination, and comprehensive diagnostic workup.

The diagnostic and prognostic utility of repetitive nerve stimulation in patients with myasthenia gravis.

Repetitive nerve stimulation (RNS) is a standard test for the diagnosis of myasthenia gravis (MG), where decrement of compound muscle action potentials (CMAP) corresponds to clinical muscle fatigability. Our aim was to ascertain the diagnostic and prognostic utility of RNS in MG patients. This study included MG patients treated between 01/2000 and 12/2016, with an observational period of at least one year and a minimum of two neurological examinations.

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis.

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.

Feasibility of a smartphone app to monitor patient reported outcomes in multiple sclerosis: The haMSter interventional trial.

Background: Monitoring of patient outcomes in multiple sclerosis (MS) is fundamental for individualized treatment decisions. So far, these decisions have been motivated by conventional outcomes, i.e.

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study.

Background: Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted.

Methods: We used a nationwide approach to collect Austrian patients with genetically confirmed CMS.

Retinal Layer Thinning After Optic Neuritis Is Associated With Future Relapse Remission in Relapsing Multiple Sclerosis.

Background And Objectives: Remission of relapses is an important contributor to both short- and long-term prognosis in relapsing multiple sclerosis (RMS). In MS-associated acute optic neuritis (MS-ON), retinal layer thinning measured by optical coherence tomography (OCT) is a reliable biomarker of both functional recovery and the degree of neuroaxonal damage. However, prediction of non-ON relapse remission is challenging.

Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study.

Background: Third vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination.

Methods: In this prospective multicenter study on 292 pwMS and 46 healthy controls (HC), who had all received two vaccinations prior to study enrollment, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after third vaccination. PwMS were categorized as follows: untreated (N-DMT, n = 32), receiving disease-modifying therapy (DMT) with expected humoral response (er-DMT: interferon-beta preparations, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, cladribine, alemtuzumab; n = 120) or no expected humoral response (nr-DMT: S1PMs, CD20mAb; n = 140).

Impact of vaccination on COVID-19 outcome in multiple sclerosis.

Background: COVID-19 continues to challenge neurologists in counselling persons with multiple sclerosis (pwMS) regarding disease-modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID-19 outcome in pwMS.

Methods: We included pwMS with PCR-confirmed COVID-19 diagnosis from a nationwide population-based registry.

Long-term outcome after COVID-19 infection in multiple sclerosis: a nation-wide multicenter matched-control study.

Background: Long-term outcome after COVID-19 in patients with multiple sclerosis (pwMS) is scarcely studied and controlled data are lacking.

Objective: To compare long-term outcome after COVID-19 in pwMS to a matched control group of pwMS without COVID-19.

Methods: We included pwMS with PCR-confirmed diagnosis of COVID-19 and ≥6 months of follow-up available and, as a control group, pwMS matched 1:1 for age, sex, disability level and disease-modifying treatment type.

Has the pandemic changed treatment strategy in multiple sclerosis?

Background: Social distancing measures during the Covid-19 pandemic reduced access to health care and concerns were raised over the safety of immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (MS).

Objective: To investigate changes in DMT prescription before and during the pandemic in a large and well-characterized real-world cohort of MS patients.

Methods: From the Vienna MS database (VMSD) we extracted MS patients who were initiated on a new DMT (both treatment-naïve and switching) between January 1st 2017 and December 31st 2021.