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 |