Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Neurol Res and Elmer Press Inc
Journal website https://jnr.elmerpub.com

Original Article

Volume 16, Number 4, December 2026, pages 250-262

Modeling Early Neurologic Trajectories After Elevated Leg Positioning in Acute Moderate Ischemic Stroke: A Secondary Analysis of the LEG-UP Randomized Feasibility Study

Figure

↓  Figure 1. Neurologic trajectory and change in NIHSS score from baseline to day 7, according to treatment group. (a) Individual patient trajectories in NIHSS score from baseline to day 7 in the control group (25 patients) and the elevated leg positioning (ELP) group (25 patients). Each line represents one patient and connects the baseline and day-7 NIHSS scores. (b) The mean NIHSS score at baseline and day 7 in each treatment group; error bars indicate 95% CIs. (c) The change in NIHSS score from baseline to day 7 (day-7 score minus baseline score) in each treatment group. Boxes indicate the interquartile range, horizontal lines indicate the medians, and whiskers indicate the most extreme values within 1.5 times the interquartile range; individual observations are shown as points. (d) The change in NIHSS score from baseline to day 7 in the ELP group according to treatment adherence, with patients categorized as having received uninterrupted ELP (21 patients) or interrupted ELP (four patients). More negative values in (c) and (d) indicate greater reductions in NIHSS score and therefore greater improvement in neurologic status. CI: confidence interval; ELP: elevated leg positioning; NIHSS: National Institutes of Health Stroke Scale.
Figure 1.

Tables

↓  Table 1. Baseline Characteristics and Clinical Outcomes by Randomized Group
 
CharacteristicControlELPP valuea
aP values are descriptive and were calculated with Welch t tests for continuous variables, Wilcoxon rank-sum tests for baseline NIHSS, NIHSS reduction, and mRS, and a Welch t test for day-7 NIHSS, and Fisher exact tests for categorical variables. bAll other participants had a pre-morbid mRS score of 0. cProportion of luminal narrowing as recorded in the parent study. dInternal carotid artery includes intracranial and extracranial segments; the P value is an overall test across categories. eReduction in NIHSS score of 4 or more points from baseline to day 7. fmRS score of 0 to 2 at 90 days. Baseline, day-7, END, and SAE data were available for all 50 randomized participants. Three participants (two in control group, one in ELP group) were lost to follow-up and had no 30- or 90-day data; denominators for follow-up outcomes are therefore 23 (control) and 24 (ELP). SAEs were ascertained within 7 days of randomization; all seven deaths by 90 days occurred after day 7. ELP: elevated leg positioning; IQR: interquartile range; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; END: early neurologic deterioration; SD: standard deviation.
Baseline characteristics (all randomized: control n = 25, ELP n = 25)
  Age, mean (SD), years58.6 (15.8)60.1 (14.8)0.73
  Male sex, n/total (%)14/25 (56.0)18/25 (72.0)0.38
  Onset to randomization, mean (SD), h8.0 (6.0)7.1 (4.9)0.58
  Previous ischemic stroke, n/total (%)5/25 (20.0)4/25 (16.0)> 0.99
  Pre-morbid mRS score of 1b, n/total (%)2/25 (8.0)3/25 (12.0)> 0.99
  Hypertension, n/total (%)17/25 (68.0)20/25 (80.0)0.52
  Dyslipidemia, n/total (%)14/25 (56.0)12/25 (48.0)0.78
  Diabetes mellitus, n/total (%)9/25 (36.0)7/25 (28.0)0.76
  Congestive heart failure, n/total (%)2/25 (8.0)3/25 (12.0)> 0.99
  Atrial fibrillation, n/total (%)0/25 (0.0)0/25 (0.0)> 0.99
  Ischemic heart disease, n/total (%)4/25 (16.0)6/25 (24.0)0.73
  Current smoker, n/total (%)8/25 (32.0)10/25 (40.0)0.77
  Capillary blood glucose, mean (SD), mg/dL134.2 (56.7)127.4 (47.1)0.64
  Systolic blood pressure, mean (SD), mm Hg146.4 (25.5)155.6 (28.4)0.23
  Diastolic blood pressure, mean (SD), mm Hg94.4 (11.6)100.4 (15.4)0.13
  Baseline NIHSS score, median (IQR)11.0 (8.0–13.0)11.0 (9.0–14.0)0.43
  Degree of stenosis, mean (SD)c0.72 (0.18)0.73 (0.19)0.85
  Responsible vesseld, n/total (%)0.61
    Internal carotid artery4/25 (16.0)7/25 (28.0)
    Middle cerebral artery, M119/25 (76.0)17/25 (68.0)
    Middle cerebral artery, M22/25 (8.0)1/25 (4.0)
Early outcomes (all randomized: control n = 25, ELP n = 25)
  NIHSS score at day 7, mean (SD)8.9 (4.7)8.0 (4.3)0.47
  NIHSS reduction, baseline minus day 7, median (IQR)2.0 (1.0–3.0)4.0 (3.0–4.0)0.001
  Early improvemente, n/total (%)4/25 (16.0)18/25 (72.0)< 0.001
  END, n/total (%)0/25 (0.0)0/25 (0.0)> 0.99
  Serious adverse event within 7 days, n/total (%)0/25 (0.0)0/25 (0.0)> 0.99
Follow-up outcomes (participants with 90-day data: control n = 23, ELP n = 24)
  mRS score at 90 days, median (IQR)3.0 (2.0–4.5)2.0 (1.0–4.0)0.27
  Functional independencef, n/total (%)11/23 (47.8)14/24 (58.3)0.56
  30-day all-cause mortality, n/total (%)3/23 (13.0)2/24 (8.3)0.67
  90-day mortality (mRS 6), n/total (%)4/23 (17.4)3/24 (12.5)0.70

 

↓  Table 2. Primary ANCOVA Model for Day-7 NIHSS Score (N = 50)
 
PredictorβSE95% CIP valuePartial ω2
Model: day-7 NIHSS = β0 + β1 (ELP) + β2 (baseline NIHSS), fitted by ordinary least squares in all 50 randomized participants (25 per group). ELP was coded 1 for elevated leg positioning and 0 for control; a negative β1 indicates a lower day-7 score with ELP. Residual standard deviation, 1.91. The 95% CI for the ELP coefficient using HC3 heteroscedasticity-robust standard errors was −3.10 to −0.80 (P = 0.001). A randomization (permutation) test with 10,000 permutations gave P < 0.001. Partial ω2 is the adjusted proportion of variance in day-7 NIHSS attributable to allocation after accounting for baseline NIHSS. CI: confidence interval; ELP: elevated leg positioning; NIHSS: National Institutes of Health Stroke Scale; SE: standard error; ANCOVA: analysis of covariance.
Intercept−5.171.02−7.23 to −3.12< 0.001—
ELP vs. control−1.950.55−3.04 to −0.850.00080.19
Baseline NIHSS score (per 1-point increase)1.350.091.17 to 1.53< 0.001—

 

↓  Table 3. Neurologic, Functional, and Safety Outcomes by Randomized Group
 
OutcomeControlELPBetween-group difference (95% CI)aP value
aDifference in NIHSS points (ELP minus control) for day-7 NIHSS; risk difference in percentage points (ELP minus control) for binary outcomes, with Newcombe hybrid-score 95% CIs. P values for binary outcomes are from Fisher exact tests; for day-7 NIHSS, from the ANCOVA (adjusted) or an unadjusted t test. bEstimated marginal means from the ANCOVA in Table 2, evaluated at the mean baseline NIHSS score (10.78). cReduction in NIHSS score of 4 or more points from baseline to day 7. With no events in either group, the CI for early neurologic deterioration and serious adverse events reflects only the sample size (an event-rate difference of up to about 13 percentage points cannot be excluded). Follow-up outcomes are exploratory, and no multiplicity adjustment was applied. ELP: elevated leg positioning; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; ANCOVA: analysis of covariance.
Day-7 NIHSS score (n = 25 per group)
  Adjusted mean (95% CI)b9.39 (8.62 to 10.17)7.45 (6.67 to 8.22)−1.95 (−3.04 to −0.85)0.0008
  Unadjusted mean (SD)8.9 (4.7)8.0 (4.3)−0.92 (−3.49 to 1.65)0.47
Early events (n = 25 per group)
  Early improvementc, n/total (%)4/25 (16.0)18/25 (72.0)56.0 (29.0 to 72.7)< 0.001
  Early neurologic deterioration, n/total (%)0/25 (0.0)0/25 (0.0)0.0 (−13.3 to 13.3)> 0.99
  Serious adverse event within 7 days, n/total (%)0/25 (0.0)0/25 (0.0)0.0 (−13.3 to 13.3)> 0.99
Follow-up outcomes (control n = 23, ELP n = 24)
  mRS score 0–2 at 90 days, n/total (%)11/23 (47.8)14/24 (58.3)10.5 (−16.9 to 35.8)0.56
  30-day all-cause mortality, n/total (%)3/23 (13.0)2/24 (8.3)−4.7 (−24.7 to 14.8)0.67
  90-day mortality (mRS 6), n/total (%)4/23 (17.4)3/24 (12.5)−4.9 (−26.3 to 16.3)0.70

 

↓  Table 4. Sensitivity and Robustness Analyses of the ELP Effect on Day-7 NIHSS Score
 
AnalysisNAdjusted difference, ELP vs control (95% CI)P value
All models estimate the ELP-minus-control difference in day-7 NIHSS score (negative values favor ELP) except for the unadjusted and change-score rows, which are not adjusted for baseline NIHSS as indicated. No bootstrap replicate failed. Bootstrap medians are shown with their intervals; BCa intervals are bias-corrected and accelerated. aSBP, systolic blood pressure at randomization; covariates were added as a sensitivity analysis only. bFour observations exceeded the threshold and were removed. ANCOVA: analysis of covariance; BCa: bias-corrected and accelerated; ELP: elevated leg positioning; NIHSS: National Institutes of Health Stroke Scale.
Regression-based analyses
  Primary ANCOVA (model-based standard errors)50−1.95 (−3.04 to −0.85)< 0.001
  Primary ANCOVA, HC3 robust standard errors50−1.95 (−3.10 to −0.80)0.001
  Primary ANCOVA, HC2 robust standard errors50−1.95 (−3.06 to −0.83)0.001
  ANCOVA with quadratic baseline term50−1.96 (−3.03 to −0.90)< 0.001
  ANCOVA plus age, onset to randomization, baseline SBPa50−1.83 (−2.97 to −0.70)0.002
  Unadjusted difference in day-7 NIHSS50−0.92 (−3.49 to 1.65)0.47
  Change-score model (day 7 minus baseline)50−1.68 (−2.91 to −0.45)0.009
Restricted analyses (ANCOVA)
  Excluding ELP participants with a treatment interruption46−2.01 (−3.21 to −0.82)0.002
  Excluding participants who died by day 3045−1.70 (−2.57 to −0.83)< 0.001
  Participants with 90-day follow-up only47−1.83 (−2.98 to −0.68)0.003
  Excluding observations with Cook distance > 4/nb46−2.08 (−2.98 to −1.19)< 0.001
Resampling-based inference for the primary ANCOVA (2,000 bootstrap replicates)
  Bootstrap, patients resampled: median (percentile CI)50−1.92 (−2.98 to −0.84)—
  Bootstrap, patients resampled: BCa CI50−1.92 (−2.99 to −0.87)—
  Bootstrap stratified by arm: median (percentile CI)50−1.94 (−3.01 to −0.81)—
  Bootstrap stratified by arm: BCa CI50−1.94 (−2.99 to −0.81)—
  Randomization test (10,000 permutations of allocation)50—< 0.001