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From the Department of Neurology (M.C., Y.S., J.S.), Institut de Diagnostic per la Imatge IDI (S.P.), and Unit of Biostatistics (M.G.-G.), Institut d’Investigació Biomèdica de Girona Doctor Josep Trueta, Girona; Department of Neurology (J.C.), Clinical Neuroscience Research Laboratory (T.S., O.M., J.C.), and Department of Neuroradiology (J.M.P.), Hospital Clínico Universitario, Santiago de Compostela, Universidad de Santiago de Compostela; and Department of Neurosciences (A.D.), Hospital Universitari Germans Trias i Pujol, Universidad Autònoma de Barcelona, Badalona, Spain.
Address correspondence and reprint requests to Dr. Antoni Dávalos, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ctra de Canyet s/n, E-08916 Badalona, Barcelona adavalos.germanstrias{at}gencat.net
Background: Excitotoxic and inflammatory mechanisms have been demonstrated as mediating early neurologic deterioration (END) in patients with cerebral infarction. Here we investigate whether molecular markers associated with END are related to the volume and outcome of the diffusion weighted image (DWI) lesion in acute ischemic stroke.
Methods: MRI was performed on admission and at 72 hours in 197 patients with acute hemispheric infarction of <12 hours’ duration. DWI lesion enlargement was calculated as the absolute difference between volumes on admission and day 3 of evolution. NIH Stroke Scale was scored at the same intervals. END was defined as an increase 
4 points within the 3 days. Glutamate, l-arginine, interleukin-6 (IL-6), and tumor necrosis factor-
levels were analyzed in blood samples obtained on admission.
Results: DWI lesion growth was found in 144 (73%) patients (median increase 38 [6.5, 83.4] cm3) and END occurred in 58 (29.4%) patients. Baseline glutamate (r = 0.71), l-arginine (r = –0.35), and IL-6 levels (r = 0.50) showed a high and significant correlation with the DWI lesion enlargement (all p < 0.001). After adjustment for potential confounders, glutamate levels were the only molecular marker associated with DWI lesion enlargement at 72 hours (β = 0.21; SD = 0.07; p = 0.004).
Conclusions: Molecular markers of early neurologic deterioration may play a role as mediators of lesion growth in cerebral ischemia. Plasma glutamate concentration is the most powerful and independent predictor biomarker of lesion enlargement in the acute phase of ischemic stroke, and so may well be useful as a signature of tissue at risk of infarction.
GLOSSARY: CBF = cerebral blood flow; CBV = cerebral blood volume; DWI = diffusion-weighted imaging; END = early neurologic deterioration; FLAIR = fluid-attenuated inversion recovery; IL-6 = interleukin-6; MTT = mean transient time; NIHSS = NIH Stroke Scale; NO = nitric oxide; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; T2-WI = T2-weighted imaging; TNF = tumor necrosis factor-.
Supplemental data at www.neurology.org
e-Pub ahead of print on October 29, 2008, at www.neurology.org.
Supported by the Fondo de Investigaciones Sanitarias del ISC III PI021083, the Institut d’Investigació Biomèdica de Girona, the Fundación de Investigación Médica Mútua Madrileña, and the RETICS-RD06/0026.
Disclosure: The authors report no disclosures.
Received October 19, 2007. Accepted in final form June 18, 2008.
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