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Body iron stores and early neurologic deterioration in acute cerebral infarction

From the Sections of Neurology (Drs. Dávalos and Armengou) and Endocrinology (Dr. Fernandez-Real), Hospital Universitari Doctor Josep Trueta, Girona; Department of Neurology (Drs. Castillo and Cacabelos), Complexo Hospitalario Universitario de Santiago (Hospital Xeral de Galicia), Santiago de Compostela; Lipids and Cardiovascular Epidemiology Unit (Dr. Marrugat), Institut Municipal d’Investigació Mèdica de Barcelona; and Department of Physiology (Dr. Rama), University of Barcelona, Spain.

Address correspondence and reprint requests to Dr. A. Dávalos, Section of Neurology, Hospital Universitari Doctor Josep Trueta, Avda Francia s/n, 17007 Girona, Spain.

BACKGROUND: Iron-dependent free radicals formation has been related to greater damage in cerebral ischemia. The authors analyzed whether increased body iron stores were associated with early neurologic worsening and excitatory amino acid release in patients with acute ischemic stroke.

METHODS: Ferritin, total iron, and glutamate concentrations in plasma and CSF were measured on admission in 100 consecutive patients with a cerebral infarction of <24 hours’ duration. The authors diagnosed progressing stroke when the Canadian Stroke Scale score decreased one or more points between admission and 48 hours. Cranial CT was performed on admission and repeated on days 4 to 7 of hospitalization.

RESULTS: Ferritin concentrations in plasma (median 391, range 119 to 500 versus 148, 21 to 399 ng/mL) and in CSF (17.4, 6.8 to 82, versus 4.8, 0.6 to 14 ng/mL) were significantly higher in the 45 patients with subsequent progressing stroke than in those with nonprogressing stroke (p < 0.001). There was a positive correlation between ferritin and glutamate concentrations in plasma (r = 0.81, p < 0.001) and CSF (r = 0.64, p < 0.001). Plasma ferritin concentrations >275 ng/mL in plasma (OR, 33.5; 95% CI, 4.7 to 235) and >11 ng/mL in CSF (OR, 11.4; 95% CI, 3.1 to 41) were independently and significantly related to early neurologic worsening. The effect was reduced by >60% after controlling for glutamate concentrations, but remained significant.

CONCLUSIONS: High plasma and CSF ferritin concentrations within the first 24 hours from the onset of ischemic stroke are associated with early neurologic deterioration. Increased body iron stores may contribute to stroke progression by enhancing the cytotoxic mechanisms in cerebral ischemia.

Key words: Amino acids—Cerebral infarction—Free radicals—Stroke.

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