Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Nadja Scherbakov, Michael Knops, Nicole Ebner, Miroslava Valentova, Anja Sandek, Ulrike Grittner, Pius Dahinden, Stefan Hettwer, Jörg C Schefold, Stephan von Haehling, Stefan D Anker, Michael Joebges, Wolfram Doehner, Nadja Scherbakov, Michael Knops, Nicole Ebner, Miroslava Valentova, Anja Sandek, Ulrike Grittner, Pius Dahinden, Stefan Hettwer, Jörg C Schefold, Stephan von Haehling, Stefan D Anker, Michael Joebges, Wolfram Doehner

Abstract

Background: C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.

Methods: Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m(2)) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA.

Results: CAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation.

Conclusions: CAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.

Keywords: C‐terminal Agrin Fragment; Muscle wasting; Physical performance; Post‐stroke rehabilitation; Skeletal muscle mass; Stroke.

Figures

Figure 1
Figure 1
Structure and cleavage sites of agrin.
Figure 2
Figure 2
Hand grip strength of stroke patients compared to healthy controls (***p ###p < 0.001 vs. admission).
Figure 3
Figure 3
CAF22 plasma level in stroke‐patients at admission to rehabilitation centre and at discharge compared to controls: All patients (A); Female patients (B); Male patients (C) (***p ###p < 0.001 vs. admission).

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