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Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study.

ABSTRACT: Several studies have attempted to reduce diagnostic delay and identify biomarkers for drug development in amyotrophic lateral sclerosis (ALS). In this study, we aimed to evaluate the diagnostic accuracy for ALS of cerebrospinal fluid (CSF) neurofilament (Nf), Tau protein, and inflammatory factors such as interleukin (IL)-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor (GMCSF) in Chinese patients. Our prospective study measured the concentration of phosphorylated Nf heavy chain (pNfH), Nf light chain (NfL), Tau, pTau, and inflammatory factors in the CSF of 85 patients. Detailed clinical data and laboratory, neuroimaging, and neurophysiological findings were recorded. The concentrations of pNfH and NfL were higher in the ALS group than in the control group. At the 1104 pg/mL pNfH cutoff, the specificity was 68.8%, the sensitivity 100%, and the area under the curve (AUC) 0.907. At the 1,139 pg/mL NfL cutoff, the specificity was 56.3%, the sensitivity 96.2%, and the AUC 0.775. There was no significant difference in the concentrations of Tau, pTau, IL-2, IL-6, IL-10, IL-15, and GMCSF between the ALS and control groups (p > 0.05). In the ALS group, the concentration of pNfH in the CSF was correlated with disease duration (r = -0.475, p < 0.001). This is the first prospective study to confirm the diagnostic value of Nf for ALS in Chinese patients.

SUBMITTER: Li DW

PROVIDER: S-EPMC6121092 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study.

Li Da-Wei DW Ren Haitao H Jeromin Andreas A Liu Mingsheng M Shen Dongshao D Tai Hongfei H Ding Qingyun Q Li Xiaoguang X Cui Liying L

Frontiers in neurology 20180828

Several studies have attempted to reduce diagnostic delay and identify biomarkers for drug development in amyotrophic lateral sclerosis (ALS). In this study, we aimed to evaluate the diagnostic accuracy for ALS of cerebrospinal fluid (CSF) neurofilament (Nf), Tau protein, and inflammatory factors such as interleukin (IL)-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor (GMCSF) in Chinese patients. Our prospective study measured the concentration of phosphorylated Nf he ...[more]

PMID: 30210445

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Project description:Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.

Project description:BackgroundGastrostomy feeding is commonly used to support patients with amyotrophic lateral sclerosis who develop severe dysphagia. Although recommended by both the American Academy of Neurology and the European Federation of Neurological Societies, currently little evidence indicates the optimum method and timing for gastrostomy insertion. We aimed to compare gastrostomy insertion approaches in terms of safety and clinical outcomes.MethodsIn this large, longitudinal, prospective cohort study (ProGas), we enrolled patients with a diagnosis of definite, probable, laboratory supported, or possible amyotrophic lateral sclerosis who had agreed with their treating clinicians to undergo gastrostomy at 24 motor neuron disease care centres or clinics in the UK. The primary outcome was 30-day mortality after gastrostomy. This study was registered on the UK Clinical Research Network database, identification number 9923.FindingsBetween Nov 2, 2010, and Jan 31, 2014, 345 patients were recruited of whom 330 had gastrostomy. 163 (49%) patients underwent percutaneous endoscopic gastrostomy, 121 (37%) underwent radiologically inserted gastrostomy, 43 (13%) underwent per-oral image-guided gastrostomy, and three (1%) underwent surgical gastrostomy. 12 patients (4%, 95% CI 2·1-6·2) died within the first 30 days after gastrostomy: five (3%) of 163 after percutaneous endoscopic gastrostomy, four (3%) of 121 after radiologically inserted gastrostomy, and three (7%) of 43 after per-oral image-guided gastrostomy (p=0·46). Including repeat attempts in 14 patients, 21 (6%) of 344 gastrostomy procedures could not be completed: 11 (6%) of 171 percutaneous endoscopic gastrostomies, seven (6%) of 121 radiologically inserted gastrostomies, and three (6%) of 45 per-oral image-guided gastrostomies (p=0·947).InterpretationThe three methods of gastrostomy seemed to be as safe as each other in relation to survival and procedural complications. In the absence of data from randomised trials, our findings could inform clinicians and patients in reaching decisions about gastrostomy and will stimulate further research into the nutritional management in patients with amyotrophic lateral sclerosis.FundingMotor Neurone Disease Association of Great Britain and Northern Ireland (MNDA) and the Sheffield Institute for Translational Neuroscience (SITraN).

Dataset Information

Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study.

Publications

Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study.

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