Progression of ischaemic stroke and excitotoxic aminoacids

Mechanisms involved in progression of stroke are little understood. Studies in animals have shown an association between neuronal death mediated by excitatory aminoacids and deterioration in focal cerebral ischaemia. We looked for an association between concentrations of glutamate and glycine in plasma and cerebrospinal fluid (CSF) and early progression in a prospective study of 128 patients with acute ischaemic stroke.

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 stroke onset when cerebral oedema had been excluded on a previous cranial computed tomography. Ischaemic stroke was judged to be in progression 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 plasma and CSF glutamate concentrations on progression was analysed by logistic regression.

43 (33.6%) patients had progressing ischaemic stroke. Concentrations of glutamate and glycine in plasma and CSF were higher in patients with progressing stroke than in those with stable cerebral infarcts (p < 0.0001). There was a significant linear correlation between CSF and plasma concentrations of glutamate (r = 0.79, p < 0.001). The positive predictive value of a plasma glutamate concentration of more than 200 mumol/L for progression of ischaemic stroke was 97% (95% CI 85-100). Glutamate concentrations of more than 200 mumol/L in plasma and of more than 8.2 mumol/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).

Early neurological progression of acute ischaemic stroke is associated with high concentrations of glutamate in blood and CSF. Measurement of plasma glutamate may be useful for the early detection of those patients with acute stroke who will deteriorate during 48 h after onset.