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Table 1 Key NfL studies for the diagnosis of MND. The table displays a list of studies dealing with NfL role in the differential diagnosis of MND according to current literature

From: Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers

Study Biomatrix Method ALS sample size (n) Disease controls (n) Type of comparison Sensitivity Specificity Cut-off value AUC
Reijn, 2009 [65] CSF sandwich-ELISA 32 ALS-mimic disorders (26) ALS vs ALS mimics 75% 79% 22.6 ng/L 0.79
Tortelli, 2012 [66] CSF ELISA test Uman Diagnostic AB; Umea, Sweden 37 Neurodegenerative diseases (21)
CIDP (25)
ALS vs all non-ALS 78.4% 72.5% 1981 ng/l 0.79 (CI 0.69–0.87)
Steinacker, 2016 [64] CSF Elisa test IBL, HamburgGermany 253 (including 20 fALS and 11 PLS) MND mimics (85)
Other neurological diseases (117)
MND vs MND mimics 77% (CI 71–82%) 88% (CI 79% to 94%) 2200 pg/mL 0.866 ± 0.023 (CI 0.821–0.911)
MND vs all non-MND not reported 85% (CI 79 to 90%) 2200 pg/mL 0.851 ± 0.019 (CI 0.813 to 0.888)
Oeckl, 2016 [63] CSF Elisa test IBL, HamburgGermany 75 (5 for each center) Neurological controls from each center with variable diagnosis (76) cumulative dataset 79% (CI 66.1–88.6%) 86.4% (CI 75.7–93.6%) 1431 pg/mL 0.86 (CI 0.79–0.93)
Paris measurement 81.1% 88.3% 2521 pg/mL not reported
Poesen, 2017 [69] CSF ELISA test Uman Diagnostic AB; Umea, Sweden 220 Disease controls (316) including 10 normal controls
Disease mimics (50)
ALS vs Disease Controls in training cohort 78.8% (71.4–85%) 72.7% (66–78.8%) 3819 pg/mL 0.809 (CI 0.763–0.849)
ALS vs Disease Controls in validation cohort 88.4% (CI 78.8–94.0%) 84.7% (CI 76.8–90.2%) 3819 pg/mL not reported
ALS vs Disease mimics 85.4% (CI 78.8–90.6%) 78.0% (CI 64.0–88.5%) 2453 pg/mL 0.863 (CI 0.808–0.908)
Gaiani, 2017 [70] CSF ELISA test Uman Diagnostic AB; Umea, Sweden 94 ALS and 20 FTD Motor neuropathies (18) including CIDP (15) and MMN (3) ALS vs all other patients 81.9% (CI 74.5–89.4%) 80.5% (CI 71.9–89%) 1843.52 pg/mL 0.91 (CI 0.87–0.95)
Controls (44): mononeuritis, primary headaches, and no objective signs of a neurologic disease ALS vs controls 88.7% (CI 79.5–97.7%) 89.4% (CI 83–96%) 1380.48 pg/mL 0.96 (CI 0.92–0.99)
Feneberg 2018 [58] CSF Elisa test IBL, HamburgGermany early phase (54) Other neurological diseases (65 CSF, 28 serum)
MND mimics (27 CSF, 21 serum)
Other MND (21 CSF, 16 serum)
early symptomatic ALS vs other neurological diseases 94% (83–99%) 86% (75–93%) 2300 pg/mL 0.95 (0.91–0.99)
early symptomatic ALS vs MND mimics 89% (71–98%) 94% (83–99%) 2183 pg/mL. (0.94–1)
late phase (135) late symptomatic ALS vs other neurological diseases 89% (82–93%) 84% (73–92%) 2146 pg/mL 0.93 (0.9–0.96)
late symptomatic ALS vs MND mimics 89% (71–98%) 89% (81–93%) 2089 pg/mL 0.96 (0.93–0.99)
serum SiMOA early phase (45) early symptomatic ALS vs other neurological diseases 88% (73–96%) 92% (80–94%) 128 pg/mL 0.92 (0.85–0.99)
early symptomatic ALS vs MND mimics 100% (84–100%) 90% (76–97%) 97 pg/mL 0.99 (0.97–1)
late phase (118) late symptomatic ALS vs other neurological diseases 79% (CI 70–86%) 92% (80–98%) 116 pg /mL 0.9 (0.83–0.97)
late symptomatic ALS vs MND mimics 100% (84–100%) 84% (76–90%) 95 pg/mL 0.97 (0.94–1)
Li, 2018
[60]
CSF ELISA test Uman Diagnostic AB; Umea, Sweden 53 (35 early phase) Controls (32)ALS mimics (7) Other neurological diseases (25) ALS vs all non-ALS 96.2% (95% CI, 87–99.5) 56.3% (95% CI, 37.7–73.6) 1139 pg/mL 0.775 (CI, 0.671–0.858
Early ALS vs all non-ALS 91.4% (CI 76.9–98.2) 59.4% (CI 40.6–76.3) 1307 pg/mL 0.772 (CI 0.654–0.866)
Rossi, 2018 [47] CSF ELISA test Uman Diagnostic AB; Umea, Sweden 190 Control group 1 (82): non-inflammatory, non-acute onset neurological disorders, including ALS-mimic diseases (31) ALS vs control group 1 76.3% (CI 69.8–81.7) 72.8% (CI 69.2–80.9) 1838 ng/L 0.775 (CI 0.713–0.837)
ALS vs ALS mimics 78.2% CI (71.2–83.5) 63.0% CI (44.1–78.4) 1540 ng/L 0.694 CI (0.572–0.817)
Control group 2 (48): acute/subacute inflammatory disorders and tumors/metastases of the nervous system ALS vs control group 2 79.2% CI (72.9–84.3) 41.3% CI (28.3–55.7) 1470 ng/L 0.542 CI (0.437–0.648)
Verde, 2019 [68] serum SiMOA 124 Disease controls (44)
Non-neurodegenerative controls (50)
Neurodegenerative diseases (65)
ALS vs disease controls 85.5% (CI 78–91.2%) 77.3% (CI 62.2 to 88.5%) 62 pg/mL 0.873 (CI 0.81 to 0.935
ALS vs non neurodegenerative controls 89.5% (CI 82.7–94.3%) 92% (CI 80.8–97.8%) 49 pg/mL 0.971 (CI 0.95 to 0.991)
ALS vs all non-ALS 85.5% (CI 78 to 91.2%) 81.8% (CI 74.9 to 87.4%) 62 pg/mL 0.887 (CI 0.849 to 0.926)
Gille, 2019 [71] serum ECL-based assay 149 PLS (11)
PMA (6)
ALS vs PLS 80.5% (Ci 73.3–86.6) 90.9% (Ci 58.7–99.8) 88 pg/ml 0.89 (Ci 0.83–0.93)
ALS vs PMA 81.2% (CI 74.0–87.1) 66.7% (CI 22.3–95.7) 86 pg/ml 0.71 (CI 0.63–0.78)
Disease controls (82): GBS (48), CIDP (20)
hSP (14)
ALS vs disease controls (hSP excluded) not reported 63.2% (CI 50.7–74.6) 139 pg/ml 0.58 (CI 0.51–0.64)
ALS vs hSP 89.3% (CI 83.1–93.7) 78.6% (CI 49.2–95.35) 55 pg/ml 0.84 (CI 0.78–0.90)
Kasai, 2019 [72] plasma SiMOA discovery cohort: 29 Non-neurological controls (29)
NMD patients (46)
ALS (discovery cohort) vs controls not reported not reported not reported 0.6659
ALS (validation cohort) vs NMD not reported not reported not reported 0.7824
CSF validation cohort: 46 ALS (discovery cohort) vs controls not reported not reported not reported 0.7206
ALS (validation cohort) vs NMD not reported not reported not reported 0.9012
Abu-Rumeileh, 2020 [67] CSF ELISA test IBL, HamburgGermany 80 healthy controls (43)
ALS mimics (46)
ALS vs healthy controls 96.3% 97.7% 1207 pg/mL 0.981 ± 0.011
ALS vs ALS mimics 91.7% 91.3% 1955 pg/ml 0.922 ± 0.031
  1. Abbreviations: ALS amyotrophic Lateral Sclerosis, AUC area under the curve, CI confidential interval, NfL neurofilament light chain, pNfH neurofilament heavy chain, CSF cerebrospinal fluid, ECL elettrochemoluminescence assay, ELISA enzyme -linked immunoadsorbent assay, MND motor neuron disorder, fALS familiar ALS, SiMoA single-molecule array, FTD Fronto-Temporal-Dementia, MMN multifocal motor neuropathy, PLS primary lateral sclerosis, CIDP Chronic inflammatory demyelinating polyneuropathy, hSP hereditary spastic paraplegia, GBS Guillain-Barre Syndrome, NMD neuromuscular disease
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