Jens Kuhle

Universitätsspital Basel · Klinik für Neurologie

Background Improving health-related quality of life (HRQoL) is an important disease management goal in persons with Multiple Sclerosis (PwMS). HRQoL decreases with increasing age and prolonged disease duration; other factors remain less understood. Objective To identify associations of multiple sclerosis (MS) disease characteristics and symptom bu...

Introduction: Understanding the prevalence of multiple sclerosis (MS) provides information for healthcare planning and helps identify trends and patterns of disease occurrence. For Switzerland, the number of persons with MS (pwMS) was last estimated at approximately 15,000 in 2016. The study’s objectives are to update estimates of MS prevalence and...

Background: Brain maturation and aging involve significant microstructural changes, resulting in functional and cognitive alterations. Quantitative MRI (qMRI) can measure this evolution, distinguishing the physiological effects of normal aging from pathological deviations. Methods: We conducted a multicentre study using qMRI metrics (R1, R2*, and Q...

Purpose Understanding the long-term safety of disease-modifying therapies for multiple sclerosis (MS) in routine clinical practice can be undertaken through registry-based studies. However, variability of data quality across such sources poses the challenge of data fit for regulatory decision-making. CLARION, a non-interventional cohort safety stud...

Objective To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B‐cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events. Methods A total of...

Background: Neurofilament light chain (NfL) has been identified as a biomarker in neuroaxonal injury. Cutaneous nerve injury resulting from inflammation and/or forced scratching may also potentially affect serum NfL (sNfL) levels. Objectives: We aimed to explore the relationship between sNfL levels and the severity of skin inflammation and scratch...

Objective Pathological studies suggest that multiple sclerosis (MS) lesions endure multiple waves of damage and repair; however, the dynamics and characteristics of these processes are poorly understood in patients living with MS. Methods We studied 128 MS patients (75 relapsing–remitting, 53 progressive) and 72 healthy controls who underwent adva...

The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer’s disease, the global organization of grey matter networks becomes more random, which is cap...

Background Patients with multiple sclerosis (PwMS) have an increased risk of infections. Objectives To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS. Design Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials. Methods...

Background and objectives: In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to co...

Inflammation of the brain is called encephalitis and may result in acute and chronic brain damage. Encephalitis can be caused by various pathogens, especially neurotropic viruses, or can occur in the context of autoimmune diseases. Encephalitis is often difficult to diagnose and to monitor precisely during the course of the disease. Thanks to highl...

Background Treatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modi...

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of g...

The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly, driven by the COVID-19 pandemic. Despite its widespread adoption, neurological complications pose a significant risk, impacting both mortality and survivors’ quality of life. Detecting these complications is challenging due to sedation and the heterogeneous nature of ECMO-asso...

Objectives Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is frequently preceded by infections. The underlying pathomechanism, however, remains poorly understood. Here, we present the clinical data of two MOGAD patients with concurrent syphilis infection and investigate the reactivity of patient-derived antibodies to...

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that...

Background and Objectives Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron level...

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to devel...

Background Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking. Objectives To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS. Methods Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizu...

A large number of disease-modifying immunotherapies are available for the treatment of people with multiple sclerosis. Many disease-modifying immunotherapies show scarce or no safety data in pregnancy and breastfeeding and are labeled as being contraindicated during these periods in the Swiss summary of product characteristics. Some disease-modifyi...

Multiple sclerosis (MS) is an immune-mediated inflammatory and degenerative disorder of the central nervous system (CNS) with heterogeneous clinical manifestations. In the last decade, the landscape of cerebrospinal fluid (CSF) and blood biomarkers as potential key tools for MS diagnosis, prognosis and treatment monitoring has evolved considerably,...

Background While potential risk factors for multiple sclerosis (MS) have been extensively researched, it remains unclear how persons with MS theorize about their MS. Such theories may affect mental health and treatment adherence. Using natural language processing techniques, we investigated large-scale text data about theories that persons with MS...

Progression independent of relapse activity (PIRA), a recent concept to formalize disability accrual in multiple sclerosis (MS) independent of relapses, has gained popularity as a potential clinical trial outcome. We discuss its shortcomings and appraise the challenges of implementing it in clinical settings, experimental trials, and research. The...

Background The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations. Objective To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or...

Background A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA–MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0–6.5) communi...

Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Ini...

Background In patients with relapsing remitting multiple sclerosis (RRMS) on low‐efficacy disease modifying therapies (DMT), the optimal strategy on how to escalate treatment once needed, remains unknown. Methods We studied RRMS patients on low‐efficacy DMTs listed in the Swiss National Treatment Registry, who underwent escalation to either medium...

Pathological data showed focal inflammation and regions of diffuse neuronal loss in the cortex of people with multiple sclerosis (MS). In this work, we applied a novel model (“soma and neurite density imaging (SANDI)”) to multishell diffusion-weighted MRI data acquired in healthy subjects and people with multiple sclerosis (pwMS), in order to inves...

Background: It is unknown whether large language models (LLMs) may facilitate time- and resource-intensive text-related processes in evidence appraisal. Objectives: To quantify the agreement of LLMs with human consensus in appraisal of scientific reporting (PRISMA) and methodological rigor (AMSTAR) of systematic reviews and design of clinical trial...

Background and objectives: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption pe...

Background: Ultra-high-resolution magnetic resonance imaging of the ex vivo brain is increasingly becoming an indispensable tool for studying the morphology and potential pathology of the brain. Despite the important role of the cerebellum in nervous system functions and motor control, as well as its potential damage in neurological diseases, it re...

Background Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS). Methods Randomized trials assessing approved DMTs in PwMS with results for at least one o...

Background The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide. Objective To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension. Methods In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg...

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practic...

Background: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course. Methods: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale...

Background In REFLEX, subcutaneous interferon beta-1a (sc IFN β-1a) delayed the onset of multiple sclerosis (MS) in patients with a first clinical demyelinating event (FCDE). Objectives This post hoc analysis aimed to determine whether baseline serum neurofilament light (sNfL) chain can predict conversion to MS and whether correlations exist betwe...

Background Treatment decisions for persons with relapsing-remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease modi...

Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two‐stage network meta‐regression prediction model that synthesized randomized trials and evaluates how treatment effects vary across patient characteristics. In this article, we extended this model to combine different source...

(1) Introduction: This pilot study aimed to analyze neurofilament light chain levels in cerebrospinal fluid (cNfL) in a cohort of children with different acute nontraumatic neurological conditions. (2) Methods: This prospective observational cohort study consisted of 35 children aged 3 months to 17 years and was performed from November 2017 to Dece...

Background and purpose In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator‐independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matte...

Anti-CD20 therapy to deplete B cells is highly efficacious in preventing new white matter lesions in patients with relapsing-remitting multiple sclerosis (RRMS), but its protective capacity against gray matter injury and axonal damage is unclear. In a passive experimental autoimmune encephalomyelitis (EAE) model whereby T H 17 cells promote brain l...

Background Evobrutinib – an oral, central nervous system (CNS)-penetrant, and highly selective Bruton’s tyrosine kinase inhibitor – has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS. Objective Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal f...

Background and Objectives Histopathologic studies have identified immunoglobulin (Ig) deposition and complement activation as contributors of CNS tissue damage in multiple sclerosis (MS). Intrathecal IgM synthesis is associated with higher MS disease activity and severity, and IgM is the strongest complement-activating immunoglobulin. In this study...

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we exam...

Neurofilament light chain (NfL) is a long-awaited blood biomarker that can provide clinically useful information about prognosis and therapeutic efficacy in multiple sclerosis (MS). There is now substantial evidence for this biomarker to be used alongside magnetic resonance imaging (MRI) and clinical measures of disease progression as a decision-ma...

Objective To assess long-term efficacy of ofatumumab treatment for up to 4 years in patients with relapsing multiple sclerosis (RMS). Design/Methods This analysis (data cut-off:25-Sep-2021) will include cumulative data from patients randomized to ofatumumab/teriflunomide in the ASCLEPIOS I/II trials (core study) and the ongoing, open-label, ALITHI...

Objective To assess NEDA-3 and NEDA-4 in RMS patients treated with ozanimod. Methods Data are from a randomized phase 3 trial (RADIANCE-NCT02047734) of oral ozanimod 0.92 mg/d vs intramuscular interferon β-1a (IFN) 30 µg/wk and an open-label extension trial (DAYBREAK-NCT02576717) of ozanimod 0.92 mg/d. NEDA-3 (no gadolinium-enhancing lesions, new/...

Objective Assess the predictive value of cognitive processing speed (CPS), using the Symbol Digit Modalities Test (SDMT) score, on disability progression in secondary progressive multiple sclerosis (SPMS). Methods SPMS patients from the Phase 3 EXPAND study (core part [CP] and core+extension part [CP+EP]) were categorized into quartiles of baselin...

Objectives The Crystal Ball model is a previously published and externally validated algorithm.¹ that helps predict the individual response to Multiple Sclerosis (MS) therapies. In this study, we investigated the contribution of Neurofilament Light (NfL) chain levels to the prediction of treatment response. Methods Data from 3 participating center...

Objective This study aims to identify the baseline profile characteristic of super-responders to siponimod in the Phase 3 EXPAND study on four domains of progression (Expanded Disability Status Scale [EDSS]; upper limb function using the 9-hole peg test [9HPT]; ambulation using the timed-25-fooot walk test [T25FWT]; and cognitive processing speed u...

Background Pragmatic trials are increasingly recognized for providing real-world evidence on treatment choices. Objective The objective of this study is to investigate the use and characteristics of pragmatic trials in multiple sclerosis (MS). Methods Systematic literature search and analysis of pragmatic trials on any intervention published up t...

Background To mimic as closely as possible a randomised controlled trial (RCT) and calibrate the real-world evidence (RWE) studies against a known treatment effect would be helpful to understand if RWE can support causal conclusions in selected circumstances. The aim was to emulate the TRANSFORMS trial comparing Fingolimod (FTY) versus intramuscula...