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Objective: The split-hand index (SI), a reliable diagnostic marker of amyotrophic lateral sclerosis (ALS), was prospectively assessed for differences across ALS subtypes and between the onset side of clinical symptoms or the dominant and contralateral sides. In addition, the prognostic utility of the SI was longitudinally assessed.
Methods: Two hundred and forty-five ALS patients underwent measurement of SI on both sides compared with 126 neuromuscular mimic disorders (NMD). A subset of patients (N = 45) underwent longitudinal assessment of SI.
Results: The SI was significantly reduced (SI 5.47(4.2), SI 9.0 (5.0); P < 0.001; SI 5.5 (4.1), SI 9.4 (5.0), P < 0.001) on both sides in all ALS patients with prominent reduction on the onset side in upper limb onset ALS (SI P < 0.001; SI P < 0.05) and in Awaji definite/probable diagnostic category (SI P < 0.05; SI P < 0.05). Longitudinal studies disclosed that the rate of SI decline correlated with the decline in ALSFRS-R (r = 0.21, P < 0.05).
Conclusion: The SI is reduced in all ALS subtypes most prominently in upper limb onset disease, on the side of clinical onset, and in patients with Awaji definite/probable diagnostic category.
Significance: The split-hand index is a reliable diagnostic and outcome biomarker across ALS subtypes and may have potential utility in a clinical trial setting, although further multicenter studies are required to confirm this.
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http://dx.doi.org/10.1016/j.clinph.2021.06.008 | DOI Listing |
Amyotroph Lateral Scler Frontotemporal Degener
September 2025
Brain and Nerve Research Centre, Concord Clinical School, University of Sydney, Concord Hospital, Sydney, Australia.
: Neck flexion (NF) weakness is a frequently observed clinical feature in amyotrophic lateral sclerosis (ALS), particularly in advanced disease. The aim of the present study was to assess whether NF weakness could be a clinical biomarker for development of respiratory dysfunction. : Sixty-two ALS patients were prospectively recruited at Brain and Nerve Research Center.
View Article and Find Full Text PDFAnal Biochem
September 2025
College of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
This study aimed to investigate potential biomarkers related to Endoplasmic reticulum (ER) stress in Amyotrophic lateral sclerosis (ALS) through a comprehensive bioinformatic approach. The gene expression profiles of ALS patients and healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. ER stress-related genes were collected from the MSigDB databases and document literature.
View Article and Find Full Text PDFAmyotroph Lateral Scler Frontotemporal Degener
September 2025
Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
: Amyotrophic lateral sclerosis (ALS) has a poorly understood preclinical phase, particularly concerning diagnostic blood markers. Our objective was to determine whether distinct patterns in routinely collected clinical and laboratory markers exist during the preclinical phase and could be incorporated to facilitate early diagnosis. : We conducted a longitudinal, retrospective, case-control study with health records of prediagnostic ALS patients (PDALS) from health maintenance organizations covering approximately 40% of the Israeli population.
View Article and Find Full Text PDFmedRxiv
August 2025
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form.
Methods: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan).
Brain
September 2025
IRCSS Fondazione Santa Lucia, European Center for Brain Research (CERC), Rome 00143, Italy.
Innate immune signaling pathways are hyperactivated in the central nervous system (CNS) of patients with Amyotrophic Lateral Sclerosis (ALS), as well as in preclinical models with diverse causative backgrounds including TDP-43, SOD1, and C9orf72 mutations. This raises an important question of whether these pathways are key pathogenic features of the disease, and whether therapeutic amelioration could be beneficial. Here, we systematically profile Type-I interferon (IFN)-stimulated gene (ISG) expression signatures using a non-biased approach in CNS tissue from a cohort of 36 individuals with ALS, including sporadic ALS (sALS; n=18), genetic ALS caused by (i) a C9orf72 hexanucleotide repeat expansion (C9-ALS; n=11), and (ii) a SOD1 mutation (SOD1-ALS; n=5), alongside age- and sex-matched individuals who died of a non-neurological cause (n=12).
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