Prognostic Value of Serum Copper for Post-Stroke Clinical Recovery: A Pilot Study

Abstract

The clinical course after ischemic stroke can vary considerably despite similar lesions and clinical status at the onset of symptoms, suggesting that individual factors modulate clinical recovery. Here, we sought to test the working hypothesis that elevated copper values provide prognostic information, and specifically predict worse clinical recovery. We further sought to support previous findings regarding metal metabolism in acute stroke. We assessed total antioxidant status, oxidative stress factors (peroxides) and metal metabolism markers (iron, copper, ceruloplasmin concentration and activity, ferritin, and transferrin) in the acute phase (2-10 days from symptom onset) in 30 patients affected by unilateral middle cerebral artery (MCA) stroke. A longitudinal assessment of clinical deficit was performed in the acute and stabilized phases (typically 6 months post-stroke) using the National Institutes of Health Stroke Scale (NIHSS). In identifying recovery-related factors, we considered effective recovery (ER), calculated as the ratio between actual NIHSS recovery and the total potential recovery. This allows an estimation of the actual recovery adjusted for the patient's initial condition. In the acute phase, clinical severity was correlated with increased peroxide concentrations, and lower iron levels. Less successful clinical recovery was correlated with increased acute copper levels, which entered a multiple regression model that explained 24% of ER variance. These pilot data suggest that, in the acute phase of an ischemic stroke, copper may provide useful information about clinical recovery.

Keywords: functional recovery; ischemic stroke; metal metabolism; oxidative stress; serum markers.

Figure 1

Relationship between stroke acute serum copper and recovery and clinical states. Top: scatter plot of the effective recovery (ER) in relationship with the total copper in acute phase, the only variable entering the regression model explaining 24% of ER variance. Bottom: clinical state scored by National Institute of Health Stroke Scale (IHSS) in acute (t0) and stabilized phase (t1) expressed in function of the total copper (x-axis) to identify single patients in terms of recovery (top section) and clinical states (bottom). It is visible that the absence of correlation of total copper with NIHSS at t0. It is also noticeable that people with total copper above 20 µmol/L in t0 recover poorly, in particular patients 26 and 28 (order determined by copper level) had minimal and mild symptoms in t0 which did not ameliorate at all. In red, the four people who did not recover at all, i.e., ER = 0, NIHSS at t0 = NIHSS at t1. In green (dots top, contours bottom), the 11 people who recovered completely (ER = 1, NIHSS at t1 = 0).