Background: The mechanisms of cellular death in the tissue surrounding an intracerebral hemorrhage (ICH) are not defined. Objective: To investigate the relationship of markers of excitotoxicity and inflammation to brain injury after ICH. Methods: A total of 124 consecutive patients with spontaneous ICH admitted within 24 hours of stroke onset were prospectively investigated. The volumes of the initial ICH, peripheral edema on days 3 to 4, and the residual cavity at 3 months were measured on CT scan. Glutamate, cytokines, and adhesion molecules were measured in blood samples obtained on admission. Stroke severity and neurologic outcome were evaluated with the Canadian Stroke Scale. Results: Poor neurologic outcome at 3 months (Canadian Stroke Scale < 7) was observed in 53 patients (43%). Stroke severity and glutamate concentrations (by each increment of 10 μmol/L, odds ratio 1.23; 95% CI 1.09 to 1.41), but not the initial volume of ICH, were independent predictors of poor outcome. In the multiple linear regression analyses, tumor necrosis factor-α concentration was correlated (r = 0.83, p < 0.0001) with the volume of perihematoma edema, and glutamate concentrations were correlated (r = 0.78, p < 0.0001) with the volume of the residual cavity. These same results were observed when lobar (n = 58) and deep (n = 66) ICH were analyzed separately. Conclusions: High plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations.

Objective: To evaluate the usefulness of a mismatch between the severity of acute clinical manifestations and the diffusion-weighted imaging (DWI) lesion in predicting early stroke outcome and infarct volume. Methods: One hundred sixty-six patients with a hemispheric ischemic stroke of <12 hours’ duration were studied. The NIH Stroke Scale (NIHSS) score and the volume of DWI lesion were measured on admission and at 72 ± 12 hours. Infarct volume was measured on T2-weighted or fluid-attenuated inversion recovery images at day 30. Early neurologic deterioration (END) was defined as an increase of ≥4 points between the two NIHSS evaluations. Thirty-eight patients received IV thrombolysis or abciximab. Clinical–DWI mismatch (CDM) was defined as NIHSS score of ≥8 and ischemic volume on DWI of ≤25 mL on admission. The adjusted influence of CDM on END, DWI lesion enlargement at 72 hours, and infarct growth at day 30 was evaluated by logistic regression analysis and generalized linear models. Results: CDM was found in 87 patients (52.4%). Patients with CDM had a higher risk of END than patients without CDM because NIHSS < 8 (odds ratio [OR], 9.0; 95% CI,1.9 to 42) or DWI lesion > 25 mL (OR, 2.0; 95% CI, 0.8 to 4.9). CDM was associated with an increase of 46 to 68 mL in the mean volume of DWI lesion enlargement and infarct growth in comparison with non-CDM. All the effects were even greater and significant in patients not treated with reperfusion therapies. Conclusions: Acute stroke patients with an NIHSS score of ≥8 and DWI volume of ≤25 mL have a higher probability of infarct growth and early neurologic deterioration. The new concept of CDM may identify patients with tissue at risk of infarction for thrombolytic or neuroprotective drugs.

Background and Purpose —The mechanisms involved in the neurological deterioration of acute lacunar strokes are unknown. Although accumulating evidence suggests that glutamate release plays a role in the progression of territorial infarctions, it remains to be established whether excitotoxicity also participates in lacunar stroke progression. We investigated whether excitatory and inhibitory amino acid concentrations in blood predict subsequent progressive motor deficits in lacunar infarctions. Methods —We studied 113 consecutive patients with lacunar infarct, defined by clinical and computed tomography/magnetic resonance imaging criteria, within the first 24 hours after stroke onset. Neurological deterioration was defined as a decrease of ≥1 points in the motor items of the Canadian Stroke Scale in the first 48 hours after admission. Glutamate, glycine, and GABA were determined by high-performance liquid chromatography in plasma samples obtained on admission. Predictive values, sensitivity, specificity, and accuracy of specific glutamate and GABA concentrations and glutamate×glycine/GABA index for progression of lacunar stroke were calculated. Results —Twenty-seven patients (23.9%) had neurological worsening. Plasma concentrations of glutamate (253±70 versus 123±73 μmol/L, mean±SD) were higher and those of GABA (140±63 versus 411±97 nmol/L) were lower in the progressing group than in the nonprogressing group (both P 200 μmol/L and GABA levels 106 had a positive predictive value of 85%. Conclusions —These findings suggest that an imbalance between the glutamate and GABA concentrations may play a role in the pathophysiology of progressing lacunar infarctions.

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-α 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; TNFα = tumor necrosis factor-α.

BACKGROUND: Flow-diverter technology has become an important stent-based embolization tool in the treatment of complex cerebrovascular pathology. We report here the experience of 4 Spanish centers with using the SILK flow-diverter (SFD) device. OBJECTIVE: To evaluate the safety and efficacy of using the SFD in the endovascular treatment of intracranial aneurysms with complex morphology. METHODS: We retrospectively examined a prospectively maintained database of patients treated with SFD devices between July 2008 and December 2013 at 1 of 4 institutions in Spain. Data regarding patient demographics, aneurysm characteristics, and technical procedure were analyzed. Angiographic and clinical findings were recorded during the procedure and at 12 months postoperatively. RESULTS: A total of 175 SFD devices were implanted in 157 patients (women/men: 119/38; mean, median, and range of age: 56.2, 56.7, and 19-80 years, respectively), who were treated in a delayed manner (3-6 months from the event) for 180 aneurysms (165 unruptured and 15 ruptured). Adverse events (acute and delayed) were observed in 28.7% of cases (45/157), and most were resolved (19.1%; 30/157). Six months after the procedure, total morbidity and mortality were 9.6% (15/157) and 3.2% (5/157), respectively. Long-term imaging follow-up showed complete occlusion, neck remnants, and residual aneurysm in 78.1% (100/128), 14.0% (18/128), and 7.8% (10/128) of cases, respectively. CONCLUSIONS: The SFD device is an effective tool for the treatment of challenging aneurysms, and allows complete occlusion within a year of the procedure in most patients, with morbidity and mortality comparable to those previously reported for similar devices.