Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study

European Journal of Neurology, Год журнала: 2024, Номер 31(9)

Опубликована: Июнь 10, 2024

To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes amyotrophic lateral sclerosis (ALS).

Язык: Английский

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Self-assessment of amyotrophic lateral sclerosis functional rating scale on the patient’s smartphone proves to be non-inferior to clinic data capture

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Фев. 22, 2025

Objective To investigate self-assessment of the amyotrophic lateral sclerosis functional rating scale–revised (ALSFRS-R) using patient's smartphone and to analyze non-inferiority clinic assessment.

Язык: Английский

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Predicting survival rate by plasma biomarkers and clinical variables in syndromes associated with frontotemporal lobar degeneration

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION Modeling the survival rate in syndromes associated with frontotemporal lobar degeneration (FTLD) is essential to assess disease trajectories. METHODS In 262 patients FTLD, we considered plasma neurofilament light chain (NfL), glial fibrillary acidic protein, brain‐derived tau, phosphorylated tau217 and amyloid beta (Aβ42/Aβ40). The FTLD Survival Score (FTLD‐SS) was calculated by β coefficients of variables independently rate. RESULTS Increased NfL levels ( p < 0.001), older age at evaluation = 0.002), positive family history 0.04), motor phenotypes 0.001) were reduced survival. predictive validity FTLD‐SS 0.75 (95% confidence interval, 0.59–0.91) 1 year. DISCUSSION shaped intensity neurodegeneration (using as proxy) together certain clinical variables. may serve a simple tool for estimation patient stratification trials. Highlights Plasma can predict (FTLD)–associated syndromes. (FTLD‐SS), computed predictors, stratification. greater atrophy frontal putamen areas.

Язык: Английский

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Phosphorylated neurofilament heavy chain (pNfH) concentration in cerebrospinal fluid predicts overall disease aggressiveness (D50) in amyotrophic lateral sclerosis

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 12, 2025

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterized by tremendous clinical heterogeneity that necessitates reliable biomarkers for the trajectory of disease. The potential phosphorylated Neurofilament-Heavy-chain (pNfH) measured in cerebrospinal fluid (CSF) to mirror disease progressiveness has repeatedly been suggested but not applicable as outcome on an individual patient-level. This was probably obfuscated before due imprecise measures progression assumed linear decline motoric function over time. primary objective therefore study if aggressiveness, quantified via D50 model, would reveal more stable correlations with pNfH. Methods ELISA-quantified pNfH CSF levels 108 patients ALS were comparatively analyzed relation three different speed analyses covariance, and non-linear regressions, respectively. These (a) D50, depicting patient’s overall (b) cFL, calculated functional loss-rate locally derived parameter speed, (c) DPR, progression-rate commonly used approximation points lost per month rating scale since symptom onset. Results All covariance showed significant main impact respective progression-speed pNfH, independent phase, presence frontotemporal dementia, analyzing laboratory, sex or onset type, while only age revealed borderline additional influence. Notably, concentration how far had progressed, neither phase nor direct regression accumulation at time lumbar puncture correlation. However, quantifying aggressiveness most pNfH-levels, compared cFL even evident contrast DPR. superiority confirmed regressions Conclusion Overall ALS, robustly correlated collection during symptomatic opens perspectives use prognostic measure future therapeutic interventions sense precision medicine.

Язык: Английский

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Advances in neurofilament light chain analysis

Advances in clinical chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Targeting senescence in Amyotrophic Lateral Sclerosis: senolytic treatment improves neuromuscular function and preserves cortical excitability in a TDP-43Q331K mouse model.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary cortex (PMC) and spinal cord. Aging key factor ALS onset progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging ALS. This promotes senescent cell accumulation-marked irreversible cell-cycle arrest, impaired apoptosis, chronic inflammation-disrupting tissue homeostasis impairing neuronal support functions. Thus, targeting senescence presents novel therapeutic strategy for Here, we investigated senolytic combination Dasatinib Quercetin (D&Q) TDP-43 Q331K mice. D&Q improved neuromuscular function reduced plasma neurofilament light chain, biomarker of axonal damage. The most pronounced improvement was cortical excitability, accompanied reductions PMC. These findings highlight potential senolytics to mitigate ALS-related dysfunction, supporting their viability as strategy. *Jose A. Viteriab, Nathan R. Kerrab, Charles D. Brennana are co-first authors.

Язык: Английский

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Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 1, 2025

The initiation of tofersen, a new specific antisense oligonucleotide (ASO) for SOD1 pathology, marked significant turning point SOD1-ALS patients. While clinical trials and early access program studies reported reduction in plasma cerebrospinal fluid (CSF) neurofilament levels, neuroinflammation following prolonged treatment was never assessed. In this multicenter study, we evaluated cohort 18 patients treated with analyzing correlations between biomarkers neurodegeneration/neuroinflammation variables indicative disease progression. NfL, NfH, CHI3L1, Serpina1 levels serum CSF were determined by semi-automated immunoassays (Ella™ technology). Generalized linear mixed models employed to investigate longitudinal trends these biomarkers. Our data highlighted progressive decrease during tofersen (MR = 0.97, 95% CI 0.94–0.99, p 0.006 MR 0.98, 0.95–1.00, 0.076 NfL NfH CSF, respectively). Conversely, SerpinA1 CHI3L1 increased over time 1.12, 1.08–1.16, < 0.0001 1.039, 1.015–1.062, 0.001 respectively), but modifications most apparent after six twelve months therapy, respectively. Disease progression rate did not correlate biomarker trends. We observed Tofersen treatment, alongside an increase neuroinflammatory markers, potentially linked immune response triggered ASO treatment. Given the limited on tofersen's long-term efficacy ALS due its recent introduction, identifying that predict outcomes such as diminished therapeutic or adverse effects is crucial. These may help better understand underlying pathomechanisms role modulating

Язык: Английский

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Motor phenotypes of amyotrophic lateral sclerosis – a three-determinant anatomical classification based on the region of onset, propagation of motor symptoms, and the degree of upper and lower motor neuron dysfunction

Neurological Research and Practice, Год журнала: 2025, Номер 7(1)

Опубликована: Апрель 27, 2025

Abstract Background In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark the disease. Distinct ALS were associated with different progression and survival. Despite its relevance for clinical practice research, there no broader consensus on classification phenotypes. Methods An expert process was performed from May 2023 to December 2024. A three-determinant anatomical proposed which based (1) region onset (O), (2) propagation symptoms (P), (3) degree upper (UMN) and/or lower neuron (LMN) dysfunction (M). Accordingly, this referred as “OPM classification”. Results Onset differentiate site first symptoms: O1) head onset; O2d) distal arm O2p) proximal O3r) trunk respiratory O3a) axial O4d) leg O4p) onset. Propagation temporal another, vertically distant body region: PE) earlier (within 12 months symptom onset); PL) later (without within onset), including established “progressive bulbar paralysis” (O1, PL), “flail-arm syndrome” (O2p, “flail-leg (O4d, PL); PN) not yet classifiable time since less than months. Phenotypes UMN LMN dysfunction: M0) balanced dysfunction; M1d) dominant M1p) pure (“primary sclerosis”, PLS); M2d) M2p) (“progressive muscle atrophy”, PMA); M3) dissociated arms legs (“brachial spastic paraparesis”), respectively. Conclusion This aimed standardize description in research – region, pattern, dysfunction. classification” contributes specifying prognosis, defining inclusion or stratification criteria trials correlate underlying disease mechanisms ALS.

Язык: Английский

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Morphological and functional assessment of the vagus nerve in multiple sclerosis

Clinical Autonomic Research, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Amyotrophe Lateralsklerose (ALS) – Diagnose und Therapie

DGNeurologie, Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

Язык: Английский

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