Thirty-five patients with acute MCA stroke were age-matched with thirty-five healthy controls (51.54 ± 10.50 vs 52.82 ± 17.88 yrs., p = 0.717). The systolic blood pressure (144.71 ± 24.44 vs 132.31 ± 16.06, P = 0.014) was higher and HDL (0.88 ± 0.21 vs 1.32 ± 0.37, P = 0.000) was lower in patients with stroke compared to controls.
Clinical, Metabolic and Neurological Disability According to Pial Collateral Status
Patients with MCA stroke were classified into those with poor (n = 12) and moderate-good (n = 23) pial collaterals. Age (52.42 ± 8.39 vs 51.09 ± 11.60, p = 0.797), BMI (27.88 ± 3.40 vs 27.73 ± 4.39, p = 0.919), total cholesterol (4.76 ± 1.26 vs 4.92 ± 0.97, p = 0.694), triglycerides (1.59 ± 0.75 vs 1.68 ± 0.77, p = 0.632), LDL (3.14 ± 1.00 vs 3.28 ± 0.89, p = 0.686), HDL (0.91 ± 0.29 vs 0.87 ± 0.15, p = 0.626), systolic blood pressure (145.00 ± 20.32 vs 144.57 ± 26.76, p = 0.961) and HbA1c (7.29 ± 3.69 vs 6.02 ± 1.16, p = 0.294) did not differ significantly between patients with poor compared to moderate-good pial collaterals (Table 1).
Table 1
Demographic, metabolic, and clinical characteristics of healthy controls and participants with acute ischemic stroke with moderate-good and poor pial collaterals expressed as mean ± SD. * Statistically significant differences between groups.
Parameters
|
All Control (n = 35)
|
All stroke
(n = 35)
|
P-value
|
Moderate-Good collateral
(n = 23)
|
Poor collateral
(n = 12)
|
P-value
|
Age (years)
|
52.82 ± 17.88
|
51.54 ± 10.50
|
0.717
|
51.09 ± 11.60
|
52.42 ± 8.39
|
0.797
|
BMI (kg/m²)
|
27.89 ± 5.06
|
27.79 ± 4.01
|
0.926
|
27.73 ± 4.39
|
27.88 ± 3.40
|
0.919
|
Systolic blood pressure (mmHg)
|
132.31 ± 16.06
|
144.71 ± 24.44
|
0.014*
|
144.57 ± 26.76
|
145.00 ± 20.32
|
0.961
|
HbA1c (%)
|
5.59 ± 0.42
|
6.45 ± 2.37
|
0.055
|
6.02 ± 1.16
|
7.29 ± 3.69
|
0.294
|
Total cholesterol (mmol/l)
|
4.95 ± 0.87
|
4.86 ± 1.07
|
0.715
|
4.92 ± 0.97
|
4.76 ± 1.26
|
0.694
|
Triglycerides (mmol/l)
|
1.60 ± 1.48
|
1.65 ± 0.75
|
0.887
|
1.68 ± 0.77
|
1.59 ± 0.75
|
0.632
|
LDL (mmol/l)
|
2.98 ± 0.72
|
3.23 ± 0.92
|
0.251
|
3.28 ± 0.89
|
3.14 ± 1.00
|
0.686
|
HDL (mmol/l)
|
1.32 ± 0.37
|
0.88 ± 0.21
|
0.000*
|
0.87 ± 0.15
|
0.91 ± 0.29
|
0.626
|
mRS at admission
|
NA
|
2.15 ± 1.48
|
NA
|
1.68 ± 1.25
|
3.00 ± 1.54
|
0.023*
|
mRS 90 days after discharge
|
NA
|
1.30 ± 1.46
|
NA
|
0.83 ± 1.04
|
2.22 ± 1.79
|
0.067
|
NIHSS at admission
|
NA
|
12.09 ± 6.30
|
NA
|
10.68 ± 5.96
|
14.67 ± 6.31
|
0.065
|
NIHSS 90 days after discharge
|
NA
|
5.23 ± 5.60
|
NA
|
3.76 ± 4.72
|
8.00 ± 6.32
|
0.120
|
The modified Rankin Scale (mRS) at admission (3.00 ± 1.54 vs 1.68 ± 1.25, p = 0.023) was significantly higher in patients with poor compared to moderate-good pial collaterals. Although not significant, the mRS at discharge (mRS: 2.22 ± 1.79 vs 0.83 ± 1.04, p = 0.067), and the National Institute of Health Stroke Scale (NIHSS) at admission (14.67 ± 6.31 vs 10.68 ± 5.96, p = 0.065) and at discharge (8.00 ± 6.32 vs 3.76 ± 4.72, p = 0.120) were higher in patients with poor compared to moderate-good pial collaterals (Table 1).
Corneal Nerve and Endothelial cell Parameters in Patients with Acute Ischemic Stroke Compared to Controls
CNFL (19.22 ± 5.78 vs 24.03 ± 5.21, p = 0.000), CNFD (30.45 ± 8.41 ± 34.62 ± 6.70, p = 0.025) and CNBD (64.20 ± 35.70 vs 97.31 ± 48.21, p = 0.002) were significantly lower in patients with MCA stroke compared to controls (Fig. 1, Table 2). There was no significant difference in corneal endothelial cell density (ECD) (2876.61 ± 374.58 vs 2924.95 ± 229.20, p = 0.790), endothelial cell area (ECA) (308.91 ± 41.19 vs 300.41 ± 21.57, p = 0.683), endothelial cell perimeter (ECP) (64.64 ± 4.33 vs 63.75 ± 2.60, p = 0.763), endothelial cell polymegathism (49.62 ± 3.61 vs 52.38 ± 5.87, p = 0.112) or pleomorphism (27.25 ± 4.64 vs 26.95 ± 5.10, p = 0.864) between patients with stroke compared to controls (Fig. 2, Table 2).
Table 2
Corneal nerve and endothelial cell measures comparing controls to patients with acute ischemic stroke and between patients with moderate-good and poor collaterals expressed as mean ± SD. * Statistically significant differences between groups tested using t-test at p ≤ 0.05 (data in bold).
Corneal Nerve Parameters
|
Control
(n = 35)
|
All stroke
(n = 35)
|
P-value
|
Moderate-Good collateral
(n = 23)
|
Poor collateral
(n = 12)
|
P-value
|
Corneal Nerve Parameters
|
CNFL, mm/mm2
|
24.03 ± 5.21
|
19.22 ± 5.78
|
0.000*
|
20.76 ± 5.22
|
16.26 ± 5.84
|
0.026*
|
CNFD, no/mm2
|
34.62 ± 6.70
|
30.45 ± 8.41
|
0.025*
|
31.70 ± 6.85
|
28.07 ± 10.74
|
0.231
|
CNBD, no/mm2
|
97.31 ± 48.21
|
64.20 ± 35.70
|
0.002*
|
72.89 ± 35.89
|
47.53 ± 30.04
|
0.044*
|
Corneal Endothelial Cell Parameters
|
Endothelial Cell
Parameters
|
Control
(n = 16)
|
All stroke
(n = 17)
|
P-value
|
Moderate-Good collateral
(n = 11)
|
Poor collateral
(n = 6)
|
P-value
|
ECD, cells/mm2
|
2924.95 ± 229.20
|
2876.61 ± 374.58
|
0.790
|
2974.11 ± 346.57
|
2697.86 ± 386.66
|
0.152
|
ECA, µm2
|
300.41 ± 21.57
|
308.91 ± 41.19
|
0.683
|
297.71 ± 36.6
|
329.44 ± 44.37
|
0.133
|
ECP, µm
|
63.75 ± 2.60
|
64.64 ± 4.33
|
0.763
|
63.54 ± 3.9
|
66.67 ± 4.68
|
0.160
|
EC Polymegathism, %
|
52.38 ± 5.87
|
49.62 ± 3.61
|
0.112
|
49.95 ± 4.14
|
49.00 ± 2.6
|
0.621
|
EC Pleomorphism, %
|
26.95 ± 5.10
|
27.25 ± 4.64
|
0.864
|
26.68 ± 5.43
|
28.28 ± 2.82
|
0.515
|
Corneal Nerve and Endothelial cell Parameters in Patients with Poor Compared to Good Pial Collaterals
CNFL (16.26 ± 5.84 vs 20.76 ± 5.22, p = 0.026) and CNBD (47.53 ± 30.04 vs 72.89 ± 35.89, p = 0.044) were significantly lower with no difference in CNFD (p = 0.231) between patients with poor compared to moderate-good collaterals (Table 2, Fig. 3). There was no significant ECD (2697.86 ± 386.66 vs 2974.11 ± 346.57, p = 0.152), ECA (329.44 ± 44.37 vs 297.71 ± 36.6, p = 0.133), ECP (66.67 ± 4.68 vs 63.54 ± 3.9, p = 0.160), endothelial cell polymegathism (49.00 ± 2.6 vs 49.95 ± 4.14, p = 0.621) or pleomorphism (28.28 ± 2.82 vs 26.68 ± 5.43, p = 0.515) between patients with poor compared to moderate-good collaterals (Fig. 2, Table 2).
Diagnostic accuracy for distinguishing Poor from Moderate-Good Collateral Patients
Table 3 and Fig. 4 show the diagnostic accuracy of CCM measures for identifying patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from good collaterals with 72% AUC (95% CI: 53–92%) and 71% AUC (95% CI: 53–90%), respectively. Using an abnormal cutoff of CNFL ≤ 16 mm/mm2 the sensitivity and specificity were 96% and 58%, respectively, and using an abnormal cutoff of CNBD ≤ 62 mm/mm2 the sensitivity and specificity were 65% and 75% according to Youden index, respectively.
Table 3
Receiver operating characteristic (ROC) curve analysis for the diagnostic accuracy of corneal confocal microscopy for identifying patients with poor compared to moderate-good collaterals.
CCM Parameters
|
AUC %
(95% Cl)
|
P value
|
Cutoff point
|
Sensitivity (%)
|
Specificity (%)
|
CNFL, mm/mm2
|
71 (53–92)
|
= 0.034
|
≤ 17
|
87
|
42
|
CNBD, branches/mm2
|
71 (53–90)
|
= 0.040
|
≤ 43
|
74
|
42
|