Accelerating Parkinson's Disease drug development with federated learning approaches.

Parkinson's Disease is a progressive neurodegenerative disorder afflicting almost 12 million people. Increased understanding of its complex and heterogenous disease pathology, etiology and symptom manifestations has resulted in the need to design, capture and interrogate substantial clinical datasets. Herein we advocate how advances in the deployment of artificial intelligence models for Federated Data Analysis and Federated Learning can help spearhead coordinated and sustainable approaches to address this grand challenge.

Single-cell Profiling of Reprogrammed Human Neural Stem Cells Unveils High Similarity to Neural Progenitors in the Developing Central Nervous System.

Background: Similar to induced pluripotent cells (iPSCs), induced neural stem cells (iNSCs) can be directly converted from human somatic cells such as dermal fibroblasts and peripheral blood monocytes. While previous studies have demonstrated the resemblance of iNSCs to neural stem cells derived from primary sources and embryonic stem cells, respectively, a comprehensive analysis of the correlation between iNSCs and their physiological counterparts remained to be investigated.

Methods: Nowadays, single-cell sequencing technologies provide unique opportunities for in-depth cellular benchmarking of complex cell populations.

Visual evoked potentials in multiple sclerosis: P100 latency and visual pathway damage including the lateral geniculate nucleus.

Objective: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS).

Methods: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging.

Longitudinal analysis of new multiple sclerosis lesions with magnetization transfer and diffusion tensor imaging.

Objective: The potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed.

Methods: Nineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI.

Blood neurofilament light levels predict non-relapsing progression following anti-CD20 therapy in relapsing and primary progressive multiple sclerosis: findings from the ocrelizumab randomised, double-blind phase 3 clinical trials.

Background: Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity and has demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing disease progression remains unclear.

Methods: We examined baseline and longitudinal blood NfL levels in 1421 persons with relapsing MS (RMS) and 596 persons with primary progressive MS (PPMS) from the pivotal ocrelizumab MS trials. NfL treatment-response and risk for disease worsening (including disability progression into the open-label extension period and slowly expanding lesions [SELs] on brain MRI) at baseline and following treatment with ocrelizumab were evaluated using time-to-event analysis and linear regression models.

Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by two major and interconnected hallmarks: inflammation and progressive neurodegeneration.

Objective: The aim of this work was to compare neurodegenerative processes, in the form of global and regional brain volume loss rates, in healthy controls (HCs) and in patients with relapsing MS (RMS) treated with ocrelizumab, which suppresses acute inflammation.

Methods: Whole brain, white matter, cortical gray matter, thalamic, and cerebellar volume loss rates were assessed in 44 HCs that were part of a substudy in the OPERA II randomized controlled trial (NCT01412333) and 59 patients with RMS enrolled in the same substudy as well as age- and sex-matched patients in OPERA I (NCT01247324) and II.

Neural correlates of digital measures shown by structural MRI: a post-hoc analysis of a smartphone-based remote assessment feasibility study in multiple sclerosis.

Background: A study was undertaken to evaluate remote monitoring via smartphone sensor-based tests in people with multiple sclerosis (PwMS). This analysis aimed to explore regional neural correlates of digital measures derived from these tests.

Methods: In a 24-week, non-randomized, interventional, feasibility study (NCT02952911), sensor-based tests on the Floodlight Proof-of-Concept app were used to assess cognition (smartphone-based electronic Symbol Digit Modalities Test), upper extremity function (Draw a Shape Test, Pinching Test), and gait and balance (Static Balance Test, Two-Minute Walk Test, U-Turn Test).

A comparative assessment of myelin-sensitive measures in multiple sclerosis patients and healthy subjects.

Introduction: Multiple Sclerosis (MS) is a common neurological disease primarily characterized by myelin damage in lesions and in normal - appearing white and gray matter (NAWM, NAGM). Several quantitative MRI (qMRI) methods are sensitive to myelin characteristics by measuring specific tissue biophysical properties. However, there are currently few studies assessing the relative reproducibility and sensitivity of qMRI measures to MS pathology in vivo in patients.

Longitudinal changes of deep gray matter shape in multiple sclerosis.

Objective: This study aimed to investigate longitudinal deep gray matter (DGM) shape changes and their relationship with measures of clinical disability and white matter lesion-load in a large multiple sclerosis (MS) cohort.

Materials And Methods: A total of 230 MS patients (179 relapsing-remitting, 51 secondary progressive; baseline age 44.5 ± 11.

Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a.

Background: Myelin water imaging is a magnetic resonance imaging (MRI) technique that quantifies myelin damage and repair in multiple sclerosis (MS) via the myelin water fraction (MWF).

Objective: In this substudy of a phase 3 therapeutic trial, OPERA II, MWF was assessed in relapsing MS participants assigned to interferon beta-1a (IFNb-1a) or ocrelizumab (OCR) during a two-year double-blind period (DBP) followed by a two-year open label extension (OLE) with ocrelizumab treatment.

Methods: MWF in normal appearing white matter (NAWM), including both whole brain NAWM and 5 white matter structures, and chronic lesions, was assessed in 29 OCR and 26 IFNb-1a treated participants at weeks 0, 24, 48 and 96 (DBP), and weeks 144 and 192 (OLE), and in white matter for 23 healthy control participants at weeks 0, 48 and 96.

Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS.

Background: In multiple sclerosis (MS), thalamic integrity is affected directly by demyelination and neuronal loss, and indirectly by gray/white matter lesions outside the thalamus, altering thalamic neuronal projections.

Objective: To assess the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ1a)/placebo on thalamic volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II; NCT01247324/NCT01412333) and in primary progressive MS (PPMS, ORATORIO; NCT01194570).

Methods: Thalamic volume change was computed using paired Jacobian integration and analyzed using an adjusted mixed-effects repeated measurement model.

Deformation-based morphometry identifies deep brain structures protected by ocrelizumab.

Background: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology.

Methods: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy.

Results: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.

Joint MRI T1 Unenhancing and Contrast-enhancing Multiple Sclerosis Lesion Segmentation with Deep Learning in OPERA Trials.

Background Deep learning-based segmentation could facilitate rapid and reproducible T1 lesion load assessments, which is crucial for disease management in multiple sclerosis (MS). T1 unenhancing and contrast-enhancing lesions in MS are those that enhance or do not enhance after administration of a gadolinium-based contrast agent at T1-weighted MRI. Purpose To develop deep learning models for automated assessment of T1 unenhancing and contrast-enhancing lesions; to investigate if joint training improved performance; to reproduce a known ocrelizumab treatment response; and to evaluate the association of baseline T1-weighted imaging metrics with clinical outcomes in relapsing MS clinical trials.

Additive and interaction effects of working memory and motor sequence training on brain functional connectivity.

Although shared behavioral and neural mechanisms between working memory (WM) and motor sequence learning (MSL) have been suggested, the additive and interactive effects of training have not been studied. This study aimed at investigating changes in brain functional connectivity (FC) induced by sequential (WM + MSL and MSL + WM) and combined (WM × MSL) training programs. 54 healthy subjects (27 women; mean age: 30.

Central nervous system atrophy predicts future dynamics of disability progression in a real-world multiple sclerosis cohort.

Background And Purpose: In an era of individualized multiple sclerosis (MS) patient management, biomarkers for accurate prediction of future clinical outcomes are needed. We aimed to evaluate the potential of short-term magnetic resonance imaging (MRI) atrophy measures and serum neurofilament light chain (sNfL) as predictors of the dynamics of disability accumulation in relapse-onset MS.

Methods: Brain gray and white matter, thalamic, striatal, pallidal and cervical spinal cord volumes, and lesion load were measured over three available time points (mean time span 2.

Regional Cerebellar Volume Loss Predicts Future Disability in Multiple Sclerosis Patients.

Cerebellar symptoms in multiple sclerosis (MS) are well described; however, the exact contribution of cerebellar damage to MS disability has not been fully explored. Longer-term observational periods are necessary to better understand the dynamics of pathological changes within the cerebellum and their clinical consequences. Cerebellar lobe and single lobule volumes were automatically segmented on 664 3D-T1-weighted MPRAGE scans (acquired at a single 1.

Classification of multiple sclerosis based on patterns of CNS regional atrophy covariance.

There is evidence that multiple sclerosis (MS) pathology leads to distinct patterns of volume loss over time (VLOT) in different central nervous system (CNS) structures. We aimed to use such patterns to identify patient subgroups. MS patients of all classical disease phenotypes underwent annual clinical, blood, and MRI examinations over 6 years.

Ventral posterior nucleus volume is associated with neuropathic pain intensity in neuromyelitis optica spectrum disorders.

Background: Neuropathic pain (NP) is frequent in neuromyelitis optica spectrum disorders (NMOSD). The ventral posterior nucleus (VPN) of the thalamus receives sensory afferences from the spinothalamic tracts and is associated with central pain in other conditions.

Objective: To investigate associations between NP and VPN volume in aquaporin-4-IgG- positive (AQP4-IgG+) NMOSD.

White matter lesion location correlates with disability in relapsing multiple sclerosis.

Background: Lesion location is a prognostic factor of disease progression and disability accrual.

Objective: To investigate lesion formation in 11 brain regions, assess correlation between lesion location and physical and cognitive disability measures and investigate treatment effects by region.

Methods: In 2355 relapsing-remitting multiple sclerosis patients from the FREEDOMS and FREEDOMS II studies, we extracted T2-weighted lesion number, volume and density for each brain region; we investigated the (Spearman) correlation in lesion formation between brain regions, studied association between location and disability (at baseline and change over 2 years) using linear/logistic regression and assessed the regional effects of fingolimod versus placebo in negative binomial models.

Efficacy of inpatient personalized multidisciplinary rehabilitation in multiple sclerosis: behavioural and functional imaging results.

Background: Although multidisciplinary rehabilitation programs are commonly used in clinical practice for patients with multiple sclerosis (MS), they are currently underexamined.

Objective: This study aims to investigate the efficacy and underlying brain mechanisms of an inpatient multidisciplinary rehabilitation.

Methods: Twenty-four patients with relapse-onset MS underwent a 4-week personalized inpatient multidisciplinary rehabilitation and three assessment sessions including MRI, clinical, cognitive and motor function evaluation.

Longitudinal patterns of cortical thinning in multiple sclerosis.

In multiple sclerosis (MS), cortical atrophy is correlated with clinical and neuropsychological measures. We aimed to examine the differences in the temporospatial evolution of cortical thickness (CTh) between MS-subtypes and to study the association of CTh with T2-weighted white matter lesions (T2LV) and clinical progression. Two hundred and forty-three MS patients (180 relapsing-remitting [RRMS], 51 secondary-progressive [SPMS], and 12 primary-progressive [PPMS]) underwent annual clinical (incl.

Volume loss in the deep gray matter and thalamic subnuclei: a longitudinal study on disability progression in multiple sclerosis.

Background: Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress throughout the disease course.

Objective: To investigate the impact and predictive value of volume loss in DGM and thalamic subnuclei on disability worsening in patients MS over a 6-year follow-up period.

Methods: Hundred and seventy-nine patients with RRMS (132 women; median Expanded Disability Status Scale, EDSS: 2.

Short timescale modulation of cortical and cerebellar activity in the early phase of motor sequence learning: an fMRI study.

Motor learning is a multi-stage process, in which the involvement of different brain regions is related to the specific stage. We aimed at characterising short timescale changes of brain activity induced by motor sequence learning. Twenty healthy volunteers performed a serial reaction time task during an MRI session in a 3 T scanner.

Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide.

Background: Teriflunomide 14 mg significantly reduced brain volume loss (BVL) and confirmed disability worsening (CDW) compared with placebo in the TEMSO core study.

Objective: To investigate the relationship between BVL from Baseline to Year 2 in the TEMSO core study and long-term CDW (Year 7) in the TEMSO long-term extension (NCT00803049).

Methods: Structural Image Evaluation using Normalization of Atrophy determined BVL.