Background
Methods
Standard protocol approvals, registrations, and patient consents
Statistical analysis
Results
SMA (n = 79) | Controls (n = 30) | |
---|---|---|
Age (year), median (IQR) | 31 (17–43) | 30 (17–44) |
Age of onset (year), median (IQR) | 1 (0–3) | |
Disease duration (year), median (IQR) | 28 (15–37) | |
Sex, n (%) | ||
Female | 41 (52) | 18 (60) |
Male | 38 (48) | 12 (40) |
SMA type, n (%) | ||
1 | 7 (9) | |
2 | 33 (42) | |
3 | 39 (49) | |
SMN2 copy number, n (%) | ||
2 | 9 (16) | |
3 | 31 (53) | |
4+ | 18 (31) | |
Unknown | 21 | |
Weight (kg), median (IQR) | 50 (33–65) | |
Height (cm), median (IQR) | 158 (145–170) | |
BMI (kg/m2), median (IQR) | 20.5 (16.1–23.4) | |
Scoliosis, n (%) | ||
Present | 50 (63) | |
Not present | 29 (37) | |
Spondylodesis, n (%) | ||
Present | 24 (30) | |
Not present | 55 (70) | |
CT supported LP, n (%) | ||
Yes | 44 (56) | |
No | 35 (44) | |
Use of a-/traumatic needle, n (%) | ||
Traumatic | 37 (47) | |
Atraumatic | 42 (53) | |
Wheelchair-use, n (%) | ||
Never | 9 (11) | |
Occasionally | 6 (8) | |
Permanently | 64 (81) | |
Mobility, n (%) | ||
Never able to walk | 40 (51) | |
Lost ability to walk | 24 (30) | |
Still able to walk | 15 (19) | |
Ventilation-use, n (%) | ||
Never | 55 (70) | |
< 16 h | 20 (25) | |
> 16 h | 4 (5) | |
PEG/feeding tube, n (%) | ||
Yes | 9 (11) | |
No | 70 (89) |
CHIT1 levels were elevated in SMA, but did not reflect disease severity
All SMA patients (n = 79) | Adult SMA patients (n = 58) | Pediatric SMA patients (n = 21) | Controls (n = 30) | |
---|---|---|---|---|
CSF CHIT1 (pg/mL), median (IQR) | 1787 (959–2866) | 1838 (1035–3133) | 1294 (883–2657) | 563 (563–971) |
Range | 563–9810 | 563–9810 | 563–8341 | 563–3058 |
Below LLOQ, n (%) | 12 (15) | 8 (14) | 4 (19) | 17 (57) |
CHIT1 levels increased during nusinersen treatment
CSF CHIT1 (pg/mL) | 14-month analysis | ||||
---|---|---|---|---|---|
n | Median (IQR) | Difference versus baseline | p value | ||
Median (range) | (%) | ||||
Overall | 58 | 2963 (1726–4179) | 775 (− 2713 to 11,103) | + 43 | < 0.0001**** |
Height < 131 cm | 8 | 6370 (3328–9980) | 4363 (826 to 11,103) | + 309 | 0.011719* |
Height > 131 cm | 50 | 2759 (1699–4014) | 545 (− 2713 to 3900) | + 29 | 0.001747** |
SMA type 1 | 6 | 2605 (1073–5731) | 1675 (− 114 to 7086) | + 180 | n.s |
SMA type 2 | 24 | 3026 (1744–4335) | 897 (− 1154 to 11,103) | + 51 | 0.000829*** |
SMA type 3 | 28 | 2847 (1710–4093) | 543 (− 2713 to 3087) | + 21 | n.s |
< 4 SMN2 copies | 30 | 3087 (1992–4528) | 1066 (− 1536 to 8220) | + 58 | 0.000960*** |
≥ 4 SMN2 copies | 13 | 2103 (1696–3789) | 495 (− 2713 to 2303) | + 22 | n.s |
Children | 19 | 2909 (1860–5091) | 984 (− 1536 to 8220) | + 76 | 0.001592** |
Adults | 39 | 3016 (1702–4088) | 495 (− 2713 to 11,103) | + 24 | 0.007929** |
ΔCHIT1 | B (CI95%) | SE B | β | R2 | ΔR2 |
---|---|---|---|---|---|
Model | 0.255 | 0.197** | |||
Constant | 2.564** (1.046; 4.081) | 0.750 | |||
Patients’ height (cm) | − 0.014* (− 0.028; − 0.000) | 0.007 | − 0.449 | ||
SMN2 copy number | − 0.222 (− 0.694; 0.250) | 0.233 | − 0.166 | ||
Age at start of therapy (year) | 0.006 (− 0.015; 0.027) | 0.010 | 0.110 |
CSF routine parameter | n | Baseline median (IQR) | 14-month analysis median (IQR) | p value |
---|---|---|---|---|
CellCount (MPt/L) | 57 | 1.0 (0.0–2.0) | 1.0 (0.15–1.0) | n.s |
Qalb (× 10–3) | 56 | 4.1 (3.3–6.1) | 4.7 (3.7–6.3) | 0.000359*** |
Protein (mg/L) | 58 | 308 (244–419) | 345 (283–443) | 0.000246*** |