PROGRESSION OF ISCHEMIC STROKE AND EXCITOTOXIC AMINO-ACIDS

Background Mechanisms involved in progression of stroke are little und erstood. Studies in animals have shown an association between neuronal death mediated by excitatory aminoacids and deterioration in focal ce rebral ischaemia. We looked for an association between concentrations of glutamate and glycine in plasma and cerebrospinal fluid (CSF) and e arly progression in a prospective study of 128 patients with acute isc haemic stroke. Methods Of 556 consecutive admissions to our emergency unit, 128 eligible patients with ischaemic stroke were included in our study. Blood and CSF samples were taken within the first 24 h from st roke onset when cerebral oedema had been excluded on a previous crania l computed tomography. Ischaemic stroke was judged to be in progressio n if the Canadian stroke scale score (1.5=maximum neurological deficit , 10=no deficit) fell by 1 or more points during the first 48 h after inclusion. Glutamate and glycine concentrations in plasma and CSF were measured by high-performance liquid chromatography. The effect of pla sma and CSF glutamate concentrations on progression was analysed by lo gistic regression. Findings 43 (33.6%) patients had progressing ischae mic stroke. Concentrations of glutamate and glycine in plasma and CSF were higher in patients with progressing stroke than in those with sta ble cerebral infarcts (p<0.0001). There was a significant linear corre lation between CSF and plasma concentrations of glutamate (r=0.79, p<0 .001). The positive predictive value of a plasma glutamate concentrati on of more than 200 mu mol/L for progression of ischaemic stroke was 9 7% (95% CI 85-100). Glutamate concentrations of more than 200 mu mol/L in plasma and of more than 8.2 mu mol/L in CSF were independently and significantly associated with progression of neurological deficit (26 .1 [6.9-98.6] and 40.9 [7.6-220], respectively). Interpretation Early neurological progression of acute ischaemic stroke is associated with high concentrations of glutamate in blood and CSF. Measurement of plas ma glutamate may be useful for the early detection of those patients w ith acute stroke who will deteriorate during 48 h after onset.