Introduction
Methods
Study population
Clinical assessments
Electrophysiology
Radiology
Statistical analysis
Baseline differences between MND patients and controls
Clinical, electrophysiological and radiological associations
Longitudinal changes
Baseline predictors of muscle weakness
Muscle | Mean % difference in relative T2-signal patients > controls (95% CI) | p value | Proportion of patients with clinical weakness MRC < 5 (95% CI) |
---|---|---|---|
Left tibialis anterior | 71.4 (32.7, 122.2) | < 0.001* | 0.43 (0.26, 0.62) |
Left quadriceps | 42.1 (14.0, 74.2) | 0.004* | 0.04 (0.005, 0.23) |
Right quadriceps | 37.9 (14.4, 63.8) | 0.002* | 0.04 (0.005, 0.23) |
Left gastrocnemius/soleus | 37.8 (11.7, 66.7) | 0.005* | 0.14 (0.05, 0.33) |
Right gastrocnemius/soleus | 37.6 (15.0, 62.4) | 0.002* | 0.11 (0.03, 0.30) |
Right hamstrings | 36.3 (7.4, 68.8) | 0.015 | 0.39 (0.23, 0.59) |
Left hamstrings | 33.7 (9.3, 60.5) | 0.008* | 0.36 (0.20, 0.55) |
Right hypothenar eminence | 31.3 (4.0, 61.7) | 0.028 | 0.61 (0.41, 0.77) |
Right tibialis anterior | 30.4 (5.5, 57.5) | 0.018 | 0.50 (0.32, 0.68) |
Right thoracic paraspinals | 26.9 (2.3, 53.5) | 0.033 | Not tested |
Left hypothenar eminence | 26.5 (5.1, 49.3) | 0.017 | 0.82 (0.63, 0.93) |
Left thoracic paraspinals | 26.1 (0.2, 54.0) | 0.049 | Not tested |
Right first dorsal interosseus | 24.7 (1.4, 49.7) | 0.040 | 0.64 (0.45, 0.80) |
Right biceps brachii | 22.8 (7.5, 38.8) | 0.004* | 0.21 (0.10, 0.41) |
Summary mean | 18.0 (6.7, 29.5) | 0.001* | Not applicable |
Right deltoid | 15.0 (0.8, 29.5) | 0.039 | 0.39 (0.23, 0.59) |
Tongue | 11.4 (1.7, 21.2) | 0.022 | Not tested |
Left first dorsal interosseous | 57.8 (− 2.8, 151.1) | 0.062 | 0.68 (0.48, 0.83) |
Left thenar eminence | 24.1 (− 26.0, 82.0) | 0.330 | 0.50 (0.32, 0.68) |
Right thenar eminence | 20.5 (− 1.8, 44.0) | 0.073 | 0.50 (0.32, 0.68) |
Left gluteus maximus | 15.7 (− 34.1, 70.3) | 0.517 | 0.04 (0.005, 0.23) |
Left deltoid | 12.6 (− 0.1, 25.7) | 0.053 | 0.32 (0.17, 0.52) |
Right gluteus maximus | 12.1 (− 21.4, 47.3) | 0.365 | 0.04 (0.005, 0.23) |
Left biceps brachii | 11.6 (− 0.2, 25.4) | 0.094 | 0.11 (0.03, 0.30) |
Left trapezius | 10.4 (− 4.9, 26.1) | 0.374 | Not tested |
Right triceps | 10.1 (− 30.3, 52.3) | 0.609 | 0.14 (0.05, 0.33) |
Right sternocleidomastoid | 8.7 (− 4.0, 21.8) | 0.173 | Not tested |
Left sternocleidomastoid | 7.9 (− 3.1, 19.0) | 0.153 | Not tested |
Splenius capitis | 5.2 (− 4.8, 15.2) | 0.302 | 0.03 (0.004, 0.22) |
Right psoas | 4.6 (− 32.5, 42.4) | 0.798 | 0.64 (0.45, 0.80) |
Left forearm compartment | 3.2 (− 27.1, 33.8) | 0.828 | Not tested |
Left psoas | 1.3 (− 46.1, 46.4) | 0.995 | 0.64 (0.45, 0.80) |
Right trapezius | 0.6 (− 11.4, 11.5) | 0.991 | Not tested |
Right forearm compartment | -8.9 (− 36.2, 17.7) | 0.502 | Not tested |
Left triceps | − 20.0 (− 52.6, 10.5) | 0.192 | 0.14 (0.03, 0.33) |
Results
Study population
Baseline differences between MND patients and controls
Muscle | Percentage differences between patients and controls (95% CI) | |||||
---|---|---|---|---|---|---|
MUNIX | p value | MUSIX | p value | CMAP | p value | |
Abductor pollicis brevis | − 50 (− 67, − 34) | < 0.001* | 17 (− 4, 39) | 0.115 | − 37.7 (− 55.3, − 20.1) | < 0.001* |
Abductor hallucis | − 50 (− 71, − 29) | < 0.001* | − 7 (− 33, 20) | 0.611 | − 41.5 (− 61.1, − 21.8) | < 0.001* |
Extensor digitorum brevis | − 44 (− 69, − 19) | 0.001* | − 21 (− 51, 10) | 0.180 | − 41.8 (− 64.0, − 19.6) | < 0.001* |
Tibialis anterior | − 39 (− 56, − 22) | < 0.001* | 43 (11, 76) | 0.011* | − 22.2 (− 40.2, − 4.3) | 0.016* |
Biceps brachii | − 36 (− 52, − 20) | < 0.001* | 4 (− 8, 16) | 0.522 | − 30.2 (− 46.6, − 13.9) | 0.001* |
Abductor digiti minimi | − 34 (− 51, − 16) | < 0.001* | 20 (− 1, 41) | 0.057 | − 29.4 (− 45.5, − 15.3) | < 0.001* |
Clinical, electrophysiological and radiological associations
Muscle | Mean (SD) dynamometry (lb) | Mean (SD) MUNIX | Clinico-radiological association coefficient (95% CI) | p value | Electro-physiological-radiological association coefficient (95% CI) | p value |
---|---|---|---|---|---|---|
Right biceps | Not tested | 129.3 (53.9) | Not tested | Not tested | 9.7 (− 128.9, 148.4) | 0.885 |
Left biceps | ||||||
Right first dorsal interosseous | 4.8 (3.5) | Not tested | − 10.9 (− 17.0, − 4.8) | 0.001* | Not tested | Not tested |
Left first dorsal interosseous | 4.7 (3.4) | − 6.6 (− 11.8, − 1.5) | 0.014* | |||
Right abductor pollicis brevis | 6.4 (4.6) | 82.8 (52.2) | − 13.7 (− 24.5, − 2.9) | 0.015* | − 74.2 (− 207.1, 58.7) | 0.258 |
Left abductor pollicis brevis | 7.0 (5.1) | 6.0 (− 3.4, 15.4) | 0.199 | |||
Right abductor digiti minimi | 3.4 (2.1) | 123.2 (68.0) | − 8.0 (− 16.4, 0.4) | 0.061 | − 86.9 (− 380.9, 207.1) | 0.543 |
Left abductor digiti minimi | 2.9 (1.9) | − 6.4 (− 12.2, − 0.6) | 0.034 | |||
Right quadriceps | 42.8 (11.5) | Not tested | − 56.6 (− 84.8, − 28.4) | < 0.001* | Not tested | Not tested |
Left quadriceps | 43.6 (12.6) | − 51.2 (− 82.0, − 20.4) | 0.002* | |||
Right tibialis anterior | 34.0 (19.8) | 83.5 (48.6) | − 93.0 (− 122.2, − 63.8) | < 0.001* | − 232.0 (− 343.1, − 120.9) | < 0.001* |
Left tibialis anterior | 36.5 (21.8) | − 108.1 (− 133.6, − 82.6) | < 0.001* |
Longitudinal changes
Muscle | Mean difference between baseline and four months (95%CI) | p value | Mean difference between baseline and 12 months (95%CI) | p value | SRM | Var ratio |
---|---|---|---|---|---|---|
Clinical scores | ||||||
ALSFRS-R | − 3.4 (− 4.9, − 1.8) | < 0.001* | − 5.7 (− 7.6, − 3.8) | < 0.001* | − 1.22 | 0.78 |
Dynamometry (lb) | ||||||
Right first dorsal interosseous | − 1.1− (− 1.9, − 0.4) | 0.005* | − 1.9 (− 2.8, − 0.9) | < 0.001* | − 0.74 | 0.86 |
Left first dorsal interosseous | − 1.0 (− 1.7, − 0.3) | 0.004* | − 2.0 (− 2.8, − 1.1) | < 0.001* | − 0.85 | 0.89 |
Right abductor pollicis brevis | − 0.2 (− 1.5, 1.2) | 0.804 | − 1.5 (− 3.2, 0.2) | 0.081 | − 0.38 | 0.79 |
Left abductor pollicis brevis | − 1.1 (− 2.9, 0.7) | 0.250 | − 2.1 (− 4.3, 0.2) | 0.068 | − 0.43 | 0.69 |
Right abductor digiti minimi | − 0.6 (− 1.3, 0.1) | 0.070 | − 1.0 (− 1.8, − 0.2) | 0.015* | − 0.36 | 0.70 |
Left abductor digiti minimi | − 0.8 (− 1.3, − 0.2) | 0.005* | − 1.4 (− 2.0, − 0.7) | < 0.001* | − 0.89 | 0.79 |
Right quadriceps | − 3.1 (− 7.4, 1.1) | 0.149 | − 4.6 (− 9.8, 0.6) | 0.085 | − 0.46 | 0.63 |
Left quadriceps | − 2.8 (− 7.6, 2.0) | 0.250 | − 3.6 (− 9.5, 2.3) | 0.234 | − 0.36 | 0.57 |
Right tibialis anterior | − 4.9 (− 10.0, 0.3) | 0.064 | − 10.7 (− 17.0, − 4.4) | 0.001* | − 0.73 | 0.85 |
Left tibialis anterior | − 8.4 (− 14.6, − 2.2) | 0.008* | − 9.3 (− 16.9, − 1.7) | 0.016* | − 0.64 | 0.79 |
MUNIX | ||||||
Biceps brachii | − 19 (− 33, − 4) | 0.013* | − 23 (− 42, − 4) | 0.017* | − 0.45 | 0.85 |
Abductor pollicis brevis | − 23 (− 33, − 12) | < 0.001* | − 33 (− 46, − 20) | < 0.001* | − 1.47 | 0.90 |
Abductor digiti minimi | − 45 (− 62, − 21) | < 0.001* | − 66 (− 92, − 41) | < 0.001* | − 1.08 | 0.72 |
Tibialis anterior | − 11 (− 17, − 5) | < 0.001* | − 20 (− 27, − 13) | < 0.001* | − 1.59 | 0.96 |
Abductor hallucis | − 1 (− 23, 6) | 0.234 | − 28 (− 45, − 11) | 0.001* | − 0.72 | 0.93 |
Extensor digitorum brevis | − 2 (− 12, 8) | 0.645 | − 10 (− 23, 2) | 0.108 | − 0.40 | 0.83 |
MUSIX | ||||||
Biceps brachii | 2 (− 1, 6) | 0.212 | 1 (− 3, 6) | 0.710 | 0.17 | 0.67 |
Abductor pollicis brevis | 5 (− 22, 33) | 0.701 | 20 (− 14, 53) | 0.253 | 0.23 | 0.21 |
Abductor digiti minimi | 6 (− 9, 21) | 0.448 | 33 (15, 51) | < 0.001* | 1.04 | 0.27 |
Tibialis anterior | 5 (− 12, 22) | 0.537 | − 3 (− 23, 17) | 0.778 | − 0.12 | 0.68 |
Abductor hallucis | 3 (− 3, 9) | 0.317 | 8 (1, 15) | 0.031* | 0.92 | 0.92 |
Extensor digitorum brevis | 1 (− 14, 16) | 0.852 | 5 (− 14, 23) | 0.621 | 0.05 | 0.83 |
CMAP | ||||||
Biceps brachii | − 0.7 (− 1.2, − 0.2) | 0.004* | − 1.2 (− 1.8 to − 0.5) | 0.001* | − 0.86 | 0.88 |
Abductor pollicis brevis | − 1.1 (− 1.6, − 0.6) | < 0.001* | − 2.1 (− 2.8 to − 1.5) | < 0.001* | − 1.36 | 0.93 |
Abductor digiti minimi | − 1.2 (− 2.0, − 0.4) | 0.002* | − 2.2 (− 3.1 to − 1.2) | < 0.001* | − 0.87 | 0.86 |
Tibialis anterior | − 0.3 (− 0.7, 0.1) | 0.191 | − 1.0 (− 1.5, − 0.5) | < 0.001* | − 0.85 | 0.89 |
Abductor hallucis | − 0.6 (− 1.2, 0.1) | 0.099 | − 1.2 (− 2.0, − 0.4) | 0.003* | − 0.66 | 0.95 |
Extensor digitorum brevis | − 0.1 (− 0.6, 0.3) | 0.553 | − 0.7 (− 1.3, − 0.1) | 0.017* | − 0.86 | 0.92 |
Muscle | Regression coefficientMean % change in relative T2-signal between baseline and four months (95%CI) | p value | Regression coefficientMean % change in relative T2-signal between baseline and 12 months (95%CI) | p value | SRM | Var ratio |
---|---|---|---|---|---|---|
Tongue | − 0.04 (− 0.09, 0.01) − 4.8 (− 11.2, 1.5) | 0.123 | − 2.4–0.02 (− 10.20.08, 5.4 0.04) | 0.540 | − 0.08 | 0.66 |
Right trapezius | − 6.90.03 (− 19.10.09, 5.20.02) | 0.251 | 0.20.001 (− 14.50.07, 14.80.07) | 0.981 | 0.06 | 0.17 |
Left trapezius | − 10.90.06 (− 22.90.1, 0.0904) | 0.066 | − 1.7–0.009 (− 16.10.08, 12.80.06) | 0.816 | − 0.02 | 0.17 |
Right sternocleidomastoid | − 3.70.02 (− 13.40.06, 6.00.03) | 0.443 | 0.3002 (− 11.50.05, 12.20.05) | 0.949 | 0.10 | 0.43 |
Left sternocleidomastoid | − 4.40.03 (− 14.50.08, 5.60.03) | 0.376 | − 4.1 0.02 (− 16.30.09, 8.20.04) | 0.502 | − 0.11 | 0.37 |
Splenius capitis | 4.20.03 (− 4.30.03, 12.80.08) | 0.321 | − 5.40.03 (− 16.00.1, 5.10.03) | 0.297 | − 0.42 | 0.47 |
Right deltoid | 2.70.009 (− 5.00.02, 10.40.04) | 0.486 | − 4.80.02 (− 14.40.05, 4.70.02) | 0.304 | − 0.27 | 0.71 |
Left deltoid | 1.90.008 (− 6.60.03, 10.40.04) | 0.654 | 4.60.02 (− 5.80.02, 15.20.06) | 0.365 | 0.08 | 0.59 |
Right biceps brachii | − 2.20.01 (− 13.80.06, 9.40.04) | 0.700 | 11.3 0.05 (− 2.9–0.01, 25.70.1) | 0.107 | 0.18 | 0.55 |
Left biceps brachii | − 3.5–0.009 (− 17.40.05, 0.10.103) | 0.597 | − 1.90.005 (− 18.60.05, 14.70.04) | 0.814 | − 0.21 | 0.26 |
Right triceps | − 13.90.06 (− 47.20.2, 18.00.07) | 0.378 | − 22.30.09 (− 65.10.2, 18.40.07) | 0.266 | − 0.19 | 0.10 |
Left triceps | − 0.00 (− 31.3–0.08, 31.2 0.08) | 0.998 | –0.00.02 (− 22.10.1, 22.10.09) | 0.708 | − 0.18 | 0.00 |
Right brachioradialis | 7.30.02 (− 15.00.05, 29.0.09) | 0.507 | 10.40.03 (− 15.40.05, 36.80.1) | 0.414 | 0.04 | 0.06 |
Left brachioradialis | 7.00.02 (− 16.80.05, 31.20.09) | 0.551 | 9.90.03 (− 19.30.06, 39.60.1) | 0.492 | 0.82 | 0.23 |
Right first dorsal interosseous | 18.4 0.1 (− 1.8–0.007, 39.80.2) | 0.067 | 31.10.2 (6.80.04, 57.40.3) | 0.010 | 0.64 | 0.43 |
Left first dorsal interosseous | − 0.002 (− 26.20.07, 24.60.07) | 0.952 | 16.10.05 (− 16.20.05, 50.40.1) | 0.311 | 0.97 | 0.41 |
Right thenar | 14.40.07 (− 7.10.03, 36.60.17) | 0.177 | 21.40.1 (− 4.90.02, 48.90.2) | 0.100 | 0.76 | 0.26 |
Left thenar | − 8.70.02 (− 42.10.1, 23.80.06) | 0.586 | − 10.0–0.03 (− 50.10.1, 29.8 0.08) | 0.607 | − 0.57 | 0.17 |
Right hypothenar | 5.50.02 (− 10.60.03, 22.00.06) | 0.491 | 13.80.04 (− 5.8, 0.02,34.4 0.1) | 0.155 | 0.27 | 0.73 |
Left hypothenar | 3.10.01 (− 12.60.05, 18.80.08) | 0.691 | 2.30.009 (− 16.20.06, 20.90.08) | 0.802 | 0.22 | 0.34 |
Right thoracic paraspinal | − 1.00.005 (− 4.40.09, 2.40.08) | 0.903 | 16.70.09 (− 3.00.01, 37.60.2) | 0.087 | 0.30 | 0.69 |
Left thoracic paraspinal | 1.60.01 (− 12.10.08, 15.50.1) | 0.811 | 4.20.03 (− 12.70.08, 21.40.14) | 0.610 | 0.24 | 0.70 |
Right psoas | 6.20.03 (− 19.90.08, 33.10.1) | 0.627 | 35.70.2 (4.60.02, 71.10.3) | 0.020 | 0.53 | 0.52 |
Left psoas | − 11.80.04 (− 42.80.1, 17.90.06) | 0.419 | − 15.70.06 (− 54.10.2, 20.90.07) | 0.382 | − 0.01 | 0.31 |
Right gluteus maximus | − 3.00.02 (− 24.30.1, 18.10.1) | 0.774 | 22.00.1 (− 3.1–0.02, 48.80.3) | 0.076 | 0.44 | 0.49 |
Left gluteus maximus | − 14.2 0.1 (− 42.30.3, 12.20.09) | 0.277 | –14.80.1 (− 49.8–0.4, 18.40.1) | 0.363 | − 0.10 | 0.53 |
Right quadriceps | 5.40.02 (− 2.5− ,0.008, 13.60.05) | 0.168 | 018.8.07 (9.00.03, 29.60.1) | < 0.001* | 0.86 | 0.90 |
Left quadriceps | 1.20.004 (− 7.40.02, 9.70.03) | 0.784 | 11.40.04 (2.90.004, 20.60.07) | 0.028 | 0.39 | 0.91 |
Right hamstrings | − 2.20.007 (− 10.20.03, 5.60.02) | 0.564 | 17.40.05 (7.70.02, 28.20.08) | < 0.001* | 0.98 | 0.93 |
Left hamstrings | 1.90.008 (− 7.10.03, 11.00.05) | 0.666 | 14.40.06 (3.30.02, 26.30.1) | 0.008* | 0.65 | 0.89 |
Right tibialis anterior | 10.70.04 (0.8004, 21.20.07) | 0.030 | 28.50.1 (15.90.06, 42.70.1) | < 0.001* | 0.82 | 0.87 |
Left tibialis anterior | 4.10.02 (− 7.90.01, 16.50.06) | 0.180 | 20.90.07 (6.00.02, 37.20.11) | 0.004* | 0.33 | 0.86 |
Right gastrocnemius/soleus | 5.60.02 (− 3.20.01, 14.70.06) | 0.200 | 18.90.07 (8.00.03, 30.60.1) | < 0.001* | 0.64 | 0.83 |
Left gastrocnemius/soleus | 0.5003 (− 8.20.04, 9.10.05) | 0.911 | 18.70.1 (8.0(0.05, 30.30.2) | < 0.001* | 0.78 | 0.88 |
Muscle-of-onset | − 0.102 (− 16.10.10, 16.0 0.07) | 0.698 | 16.60.10 (− 2.90.008, 37.3) 0.20) | 0.070 | 0.77 | 0.73 |
Region-of-onset | 2.70.01 (− 4.30.02, 9.70.04) | 0.437 | 14.10.06 (5.50.03, 23.2 0.10) | 0.001* | 0.87 | 0.89 |
Summary mean | − 0.1.0004 (− 6.20.03, 5.90.03) | 0.972 | 8.80.04 (1.30.007, 16.4 0.07) | 0.017 | 0.36 | 0.56 |