Background
Methods
Study population and ethics statement
Diagnostic criteria
Laboratory tests
Statistical analysis
Results
Characteristics of the study participants
N-NS (n=179) | S-NS (n=191) |
P
a
| S-NS |
P
b
|
P
c
|
P
d
| ||
---|---|---|---|---|---|---|---|---|
Confirmed (n=123) | Probable (n=68) | |||||||
Male | 112 (62.6%) | 149 (78.0%) |
0.001
| 97 (78.9%) | 52 (76.5%) | 0.702 |
0.003
|
0.039
|
P50 (P25-P75)e
| P50 (P25-P75) | P50 (P25-P75) | P50 (P25-P75) | |||||
Age | 54 (45-64) | 53 (46-61) | 0.661 | 52 (46-60) | 55 (45-64) | 0.373 | 0.474 | 0.869 |
Serum RPR titer | 1:1 (Negative-1:2) | 1:16 (1:4-1:64) |
<0.001
| 1:32 (1:16-1:64) | 1:2 (1:1-1:8) |
<0.001
|
<0.001
|
<0.001
|
Serum TPPA titer | 1:640 (1:320-1:1280) | 1:10240 (1:2560-1:20480) |
<0.001
| 1:20480 (1:10240-1:20480) | 1:2560 (1:1280-1:5120) |
<0.001
|
<0.001
|
<0.001
|
CSF RPR titer | Negative | 1:2 (Negative-1:4) |
<0.001
| 1:4 (1:2-1:8) | Negative |
<0.001
|
<0.001
| 1.0 |
CSF TPPA titer | Negative | 1:1280 (1:160-1:5120) |
<0.001
| 1:5120 (1:1280-1:10240) | 1:80 (1:80-1:640) |
<0.001
|
<0.001
|
<0.001
|
CSF leukocyte (cells/μL) | 4 (2-7) | 15 (6-48) |
<0.001
| 29 (12-59) | 6 (2-13) |
<0.001
|
<0.001
|
0.015
|
CSF protein (mg/L) | 390.9 (289.9-540.0) | 606.0 (418.6-884.3) |
<0.001
| 733.9 (502.0-1025.0) | 443.1 (325.8-607.2) |
<0.001
|
<0.001
| 0.183 |
CSF albumin (mg/L) | 249.0 (173.7-361.9) | 296.4 (220.0-456.2) |
0.003
| 296.4 (243.0-500.6) | 297.0 (182.7-446.2) | 0.218 |
0.001
| 0.204 |
CSF glucose (mmol/L) | 3.70 (3.40-4.20) | 3.54 (3.21-4.19) |
0.037
| 3.48 (3.12-4.08) | 3.74 (3.25-4.20) |
0.030
|
0.003
| 0.913 |
CSF chloride (mmol/L) | 124.3 (121.9-126.4) | 124.4 (121.5-126.3) | 0.696 | 124.8 (121.5-126.5) | 123.9 (121.6-125.9) | 0.303 | 0.902 | 0.330 |
CSF lactate (mmol/L) | 1.76 (1.57-2.02) | 1.89 (1.67-2.17) |
0.043
| 1.90 (1.73-2.30) | 1.83 (1.66-2.06) | 0.160 |
0.018
| 0.516 |
CSF lactate dehydrogenase (U/L) | 20.2 (16.7-27.7) | 20.2 (16.0-26.5) | 0.696 | 19.5 (16.0-23.6) | 22.2 (17.8-34.1) |
0.032
| 0.131 | 0.184 |
Intracranial pressure (mmH2O) | 135 (110-160) | 140 (110-160) | 0.604 | 140 (110-160) | 140 (100-160) | 0.882 | 0.656 | 0.692 |
Serum RPR and serum TPPA reactivity associated with S-NS
S-NS n (%) | N-NS n (%) | OR |
P
| S-NS n (%) | N-NS n (%) | OR |
P
| ||
---|---|---|---|---|---|---|---|---|---|
Serum RPR titers
|
Serum RPR titers
| ||||||||
Negative | 6(3.2) | 68(38.2) | 1.0 (Ref.) | ||||||
1:1 | 17(9.0) | 38(21.3) | 5.070 |
0.002
| ≥1:1 (vs <1:1) | 182(96.8) | 110(61.8) | 18.752 |
<0.001
|
1:2 | 21(11.2) | 36(20.2) | 6.611 |
<0.001
| ≥1:2 (vs <1:2) | 165(87.8) | 72(40.4) | 10.562 |
<0.001
|
1:4 | 18(9.6) | 13(7.3) | 15.692 |
<0.001
| ≥1:4 (vs <1:4) | 144(76.6) | 36(20.2) | 12.909 |
<0.001
|
1:8 | 16(8.5) | 8(4.5) | 22.667 |
<0.001
| ≥1:8 (vs <1:8) | 126(67.0) | 23(12.9) | 13.696 |
<0.001
|
1:16 | 24(12.8) | 5(2.8) | 54.400 |
<0.001
| ≥1:16 (vs <1:16) | 110(58.5) | 15(8.4) | 15.325 |
<0.001
|
1:32 | 26(13.8) | 7(3.9) | 42.095 |
<0.001
| ≥1:32 (vs <1:32) | 86(45.7) | 10(5.6) | 14.165 |
<0.001
|
1:64 | 35(18.6) | 1(0.6) | 396.667 |
<0.001
| ≥1:64 (vs <1:64) | 60(31.9) | 3(1.7) | 27.344 |
<0.001
|
≥1:128 | 25(13.3) | 2(1.1) | 141.667†
|
<0.001
| ≥1:128 (vs <1:128) | 25(13.3) | 2(1.1) | 13.497 |
<0.001
|
Serum TPPA titers
|
Serum TPPA titers
| ||||||||
≤1:160a
| 2(1.1) | 40(22.5) | 1.0 (Ref.) | ||||||
1:320 | 5(2.7) | 41(23.0) | 2.439 | 0.303 | ≥1:320 (vs <1:320) | 186(98.9) | 138(77.5) | 26.957 |
<0.001
|
1:640 | 7(3.7) | 32(18.0) | 4.375 | 0.078 | ≥1:640 (vs <1:640) | 181(96.3) | 97(54.5) | 21.592 |
<0.001
|
1:1280 | 18(9.6) | 34(19.1) | 10.588 |
0.003
| ≥1:1280 (vs <1:1280) | 174(92.6) | 65(36.5) | 21.607 |
<0.001
|
1:2560 | 23(12.2) | 12(6.7) | 38.333 |
<0.001
| ≥1:2560 (vs <1:2560) | 156(83.0) | 31(17.4) | 23.117 |
<0.001
|
1:5120 | 21(11.2) | 11(6.2) | 38.182 |
<0.001
| ≥1:5120 (vs <1:5120) | 133(70.7) | 19(10.7) | 20.236 |
<0.001
|
1:10240 | 29(15.4) | 5(2.8) | 116.000 |
<0.001
| ≥1:10240 (vs <1:10240) | 112(59.6) | 8(4.5) | 31.316 |
<0.001
|
≥1:20480 | 83(44.1) | 3(1.7) | 553.333‡
|
<0.001
| ≥1:20480 (vs <1:20480) | 83(44.1) | 3(1.7) | 46.111 |
<0.001
|
Screening performance of serum RPR and serum TPPA for S-NS
Parallel testing algorithm of serum RPR and serum TPPA for screening S-NS
Parallel testing format | Identification of S-NS | Identification of confirmed neurosyphilis | Identification of probable neurosyphilis | ||||||
---|---|---|---|---|---|---|---|---|---|
Sensitivity (%) | Specificity (%) | NPV (%) | Sensitivity (%) | Specificity (%) | NPV (%) | Sensitivity (%) | Specificity (%) | NPV (%) | |
RPR≥1:4, TPPA≥1:2560a
| 87.8 | 72.5 | 84.9 | 97.5 | 60.8 | 98.0 | 70.1 | 72.5 | 86.6 |
RPR≥1:2, TPPA≥1:2560 | 92.6 | 55.6 | 87.6 | 99.2 | 45.7 | 99.1 | 80.6 | 55.6 | 88.4 |
RPR≥1:4, TPPA≥1:1280 | 93.1 | 58.7 | 89.0 | 99.2 | 47.6 | 99.2 | 82.1 | 58.7 | 89.7 |
RPR≥1:2, TPPA≥1:1280 | 95.8 | 46.4 | 91.2 | 100.0 | 37.0 | 100.0 | 88.1 | 46.4 | 91.2 |
Univariate and multivariate analyses of factors predictive of S-NS
S-NS (n=191) n (%) | N-NS (n=179) n (%) |
P
a
| S-NS |
P
b
|
P
c
| ||
---|---|---|---|---|---|---|---|
Confirmed (n=123) n (%) | Probable (n=68) n(%) | ||||||
Comorbidities | |||||||
Other CNS infectionsd
| 3 (1.6) | 0 | 0.249 | 3 (2.4) | 0 | 0.067 | n.a. |
Brain injury | 7 (3.7) | 5 (2.8) | 0.636 | 6 (4.9) | 1 (1.5) | 0.364 | 1.0 |
Brain tumors | 2 (1.0) | 3 (1.7) | 0.676 | 1 (0.8) | 1 (1.5) | 0.648 | 1.0 |
Psychiatric disorders | 12 (6.3) | 2 (1.1) |
0.009
| 7 (5.7) | 5 (7.4) |
0.034
|
0.018
|
History of ischemic stroke | 36 (18.8) | 24 (13.4) | 0.156 | 19 (15.4) | 17 (25.0) | 0.618 |
0.029
|
History of hemorrhagic stroke | 0 | 4 (2.2) | 0.054 | 0 | 0 | 0.148 | 0.578 |
Hypertension | 83 (43.5) | 85 (47.5) | 0.436 | 47 (38.2) | 36 (52.9) | 0.110 | 0.444 |
Heart diseasese
| 32 (16.8) | 33 (18.4) | 0.671 | 19 (15.4) | 13 (19.1) | 0.499 | 0.902 |
Diabetes mellitus | 59 (30.9) | 40 (22.3) | 0.064 | 37 (30.1) | 22 (32.4) | 0.130 | 0.105 |
Chronic alcoholism | 5 (2.6) | 1 (0.6) | 0.216 | 5 (4.1) | 0 |
0.043
| 1.0 |
Serum biochemical parameters | |||||||
Elevated FPG (≥7.0 mmol/L) | 38 (19.9) | 24 (13.4) | 0.095 | 30 (24.4) | 8 (11.8) |
0.014
| 0.731 |
Elevated HbA1c (≥6.5%) | 36 (28.3) | 29 (25.4) | 0.612 | 22 (27.2) | 14 (30.4) | 0.787 | 0.519 |
Elevated CKf(male ≥308, female ≥192 U/L) | 30 (16.9) | 11 (6.6) |
0.003
| 19 (17.0) | 11 (16.9) |
0.006
|
0.017
|
Elevated HCYg
| 42 (32.1) | 22 (18.3) |
0.013
| 25 (32.9) | 17 (30.9) |
0.020
| 0.063 |
Elevated TG (≥1.70 mmol/L) | 41 (22.3) | 41 (24.6) | 0.616 | 22 (18.6) | 19 (28.8) | 0.237 | 0.505 |
Elevated CHOL (≥6.22 mmol/L) | 8 (4.3) | 11 (6.6) | 0.355 | 3 (2.5) | 5 (7.6) | 0.120 | 0.778 |
Elevated ALT (male ≥50, female ≥40 U/L) | 14 (7.3) | 16 (9.0) | 0.560 | 11 (8.9) | 3 (4.4) | 0.989 | 0.229 |
Elevated AST (male ≥40, female ≥35 U/L) | 21 (11.1) | 15 (8.5) | 0.407 | 16 (13.0) | 5 (7.5) | 0.205 | 0.797 |
Elevated TBIL (≥17.1 μmol/L) | 34 (18.1) | 26 (15.0) | 0.436 | 23 (18.9) | 11 (16.7) | 0.385 | 0.754 |
Elevated BUN (≥8.2 mmol/L) | 8 (4.2) | 12 (6.7) | 0.285 | 6 (4.9) | 2 (2.9) | 0.510 | 0.361 |
Elevated sCr (male ≥115, female ≥97 μmol/L) | 6 (3.1) | 12 (6.7) | 0.111 | 2 (1.6) | 4 (5.9) | 0.039 | 1.0 |
Combined effects of the independent risk factors of S-NS
Serum RPR titer <1:4 | Serum RPR titer ≥1:4 | |||||||
---|---|---|---|---|---|---|---|---|
Serum TPPA titer <1:2560 | Serum TPPA titer ≥1:2560 | Serum TPPA titer <1:2560 | Serum TPPA titer ≥1:2560 | |||||
Normal CK | Elevated CK | Normal CK | Elevated CK | Normal CK | Elevated CK | Normal CK | Elevated CK | |
S-NS | ||||||||
Female | 1.0 (Ref.) | n.a.a
|
6.500
*
(1.273-33.201)
| n.a.b
| 2.437 (0.502-11.845) | n.a.c
|
20.583
*
(5.853-72.380)
| n.a.d
|
Male | 1.264 (0.450-3.550) | 3.900 (0.734-20.709) |
9.286
*
(2.549-33.832)
|
9.750
*
(1.340-70.966)
|
4.643
*
(1.107-19.475)
| 6.500 (0.357-118.370) |
53.300
*
(18.073-157.194)
| n.a.d
|
Confirmed neurosyphilis | ||||||||
Female | 1.0 (Ref.) | n.a.a
| 9.750 (0.507-187.526) | n.a.b
| 4.875 (0.275-86.351) | n.a.c
|
104.000
*
(11.575-934.402)
| n.a.d
|
Male | 1.083 (0.095-12.329) | n.a.e
| n.a.e
|
39.000
*
(2.397-634.654)
| 11.143 (0.886-140.119) | n.a.e
|
265.200
*
(32.704-2150.534)
| n.a.d
|
Probable neurosyphilis | ||||||||
Female | 1.0 (Ref.) | n.a.a
|
5.850
*
(1.004-34.100)
| n.a.b
| 1.950 (0.320-11.888) | n.a.c
| 3.900 (0.734-20.709) | n.a.d
|
Male | 1.300 (0.427-3.959) | 4.680 (0.849-25.811) |
11.143
*
(2.913-42.620)
| 3.900 (0.297-51.196) | 3.343 (0.647-17.267) | 7.800 (0.419-145.200) |
10.920
*
(3.176-37.549)
| n.a.d
|