Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Abstract

Background: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15-16) vs. NO-IRT 7.5 (5-9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.

Keywords: angiogenin; biomarker; intensive therapy; recovery; rehabilitation.

Figure 1

Study design. Scheme showing the studied cohorts and follow-up visits when a battery of tests to assess motor and functional status was conducted together with blood samples extraction. Controls were recruited in a unique inclusion visit when blood samples were obtained.

Figure 2

Functional outcome. Temporal profile of the tested scales in IRT and NO-IRT cohorts. Note that in the 1st month significant improvements were only achieved in the IRT group. Differences were assessed with the Wilcoxon tests and the Man-Withney U for the transversal analysis. ^*p < 0.05; ^**p < 0.01, and ^***p < 0.001. Median and IQR are represented in box plots.

Figure 3

Angiogenin (ANG) blood levels during rehabilitation. (A) Bar graph showing the number of patients under IRT and NO-IRT over time, changing according to early improvements in the IRT group. (B) Graph comparing how time and type of therapy influenced the serum levels of ANG, assessed with ANOVA for repeated measures. (C) Jitter plots showing the temporal profile of ANG levels in NO-IRT and IRT groups; Differences were assessed with Wilcoxon tests, ^*p < 0.05, ^**p < 0.01. Mean with 95% CI are represented in graphs.