Background-Matrix metalloproteinase (MMP) expression is related to blood brain barrier disruption after cerebral ischemia. Moreover, MMP inhibitors reduce hemorrhagic transformation (HT) after embolic ischemia in tissue plasminogen activator (t-PA)-treated animals. We aimed to correlate plasmatic MMP levels with the appearance of intracranial bleeding complications in stroke patients treated with t-PA. Methods and Results-Serial MMP-2 and MMP-9 determinations were performed (ELISA, ng/mL) in 41 strokes involving the middle cerebral artery territory in patients who received t-PA within 3 hours of stroke onset. Blood samples were obtained at baseline (pretreatment) and at 12 and 24 hours after symptom onset.

Background and Purpose-Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment. Methods-To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (Ͻ24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA). 6.7, PϽ0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism. Conclusions-Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention. Results-Of

Background and Purpose-We sought to investigate the impact of hyperglycemia before reperfusion on long-term outcome in patients treated with intravenous tissue plasminogen activator (tPA). Methods-Of 268 consecutive patients with a nonlacunar middle cerebral artery (MCA) stroke evaluated at Ͻ3 hours after onset, 73 (27.2%) received intravenous tPA. Serum glucose was determined at baseline before tPA administration. Hyperglycemia was defined as a glucose level Ͼ140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours. Transcranial Doppler monitoring of recanalization and reocclusion was conducted during the first 24 hours. Total infarct volume was measured on CT at day 5 to 7. Modified Rankin Scale was used to assess outcome at 3 months. Results-Median NIHSS score was 17. At baseline, 31 patients (42.5%) were hyperglycemic and 42 (57.5%) normoglycemic. Early reperfusion (Ͻ6 hours) occurred in 43 patients (58.9%). Admission blood glucose correlated negatively with the degree of neurological improvement at 24 hours in reperfused (rϭϪ0.43; Pϭ0.019) but not in nonreperfused (rϭϪ0.20; Pϭ0.21) tPA-treated patients. Increased age (Pϭ0.014), history of diabetes mellitus (Pϭ0.043), admission glucose Ͼ140 mg/dL (Pϭ0.002), and early reocclusion (Pϭ0.004) were factors associated with poor outcome among reperfused patients. A logistic regression modeling revealed that only admission glucose value Ͼ140 mg/dL (odds ratio, 8.4; 95% CI, 1.76 to 40.02; Pϭ0.005) emerged as an independent predictor of poor outcome despite tPA-induced recanalization. In patients with 6-hour persistent MCA occlusion, baseline NIHSS score Ͼ15 points (Pϭ0.011) and proximal MCA occlusion (Pϭ0.039) were variables associated with poor outcome on univariate analysis. In a logistic regression model, only NIHSS score Ͼ15 points (odds ratio, 11.9; 95% CI, 1.48 to 97.1; Pϭ0.032) remained as an independent predictor of poor outcome and functional dependence at 3 months in nonreperfused tPA-treated patients. Conclusions-Hyperglycemia before reperfusion may in part counterbalance the beneficial effect of early restoration of blood flow, which translates into a worse outcome in hyperglycemic patients despite tPA-induced recanalization.

Background and Purpose-Matrix metalloproteinases (MMPs) are related to blood-brain barrier disruption, and some members of this family have been recently involved in brain bleedings. We aimed to investigate the temporal profile of MMPs and their natural inhibitors (TIMPs) after acute intracerebral hemorrhage (ICH) and to study its influence on neuroimaging and clinical outcome. Methods-MMP-2, MMP-9, and MMP-3, as well as TIMP-1 and TIMP-2, were serially determined by enzyme-linked immunosorbent assay on admission (Ͻ12 hours), and at 24 hours, 48 hours, 7 days, and 3 months in 21 ICH patients. ICH and perihematomal edema (PE) volumes were serially measured on baseline and follow-up computed tomography (48 hours, 7 days, and 3 months), just at the time of neurological assessment. Results-Deep ICH was found in 62% patients. Baseline ICH volume did not influence MMP-TIMP level. Highest levels of MMP-2 and TIMP-2 were found at baseline, for MMP-9 and TIMP-1 at 24 hours, and for MMP-3 at 24 to 48 hours. Baseline MMP-9 was positively correlated to PE volume (rϭ0.67, Pϭ0.004) and, conversely, its inhibitor TIMP-1 was negatively correlated to PE (rϭϪ0.51, Pϭ0.04). Mortality reached 35% and MMP-3 was the only MMP/TIMP related to mortality (7.5 versus 2.4 ng/mL; Pϭ0.035) and its most powerful baseline predictor (odds ratio ϭ 22, confidence interval: 1.5 to 314.2). Both MMP-9 and MMP-3 correlated to the residual scar volume at 3 months (rϭ0.68, Pϭ0.01 for baseline MMP-9, and rϭ0.86, PϽ0.001 for 24-hour MMP-3). Conclusions-A characteristic temporal profile of MMP/TIMP release exists in ICH. Increased MMP-9 is associated with PE, and increased MMP-3 is associated with mortality. Both molecules are related to residual cavity volume.

Background and Purpose-Hyperglycemia (HG) has a deleterious effect in stroke patients by accelerating ischemic brain damage; moreover, its antifibrinolytic effect may also influence reperfusion. We aimed to study the effect of acute/chronic HG on tissue-type plasminogen activator (tPA)-induced recanalization. Methods-We studied 139 consecutive stroke patients with documented intracranial artery occlusion treated with intravenous tissue-type plasminogen activator (tPA). Admission glucose levels were recorded (in mg/dL). The existence of previous chronic HG was determined by plasma levels of glycosylated hemoglobin (HbA1c, %) and fructosamine (in mol/L). Transcranial Doppler monitoring assessed complete recanalization 2 hours after tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 48 hours. Results-On admission, the median NIHSS score was 18 and mean glucose value was140Ϯ63 mg/dL. At 2 hours, 32% of patients (nϭ44)

Background and Purpose-Recently, a new definition of transient ischemic attack (TIA) has been proposed based on the duration of symptoms and diffusion-weighted imaging (DWI) findings. We investigate the value of temporal and neuroimaging data on the prognoses of TIA patients. Methods-Clinical data, symptom duration, DWI, and ultrasonographic findings were collected in 83 consecutive classical TIA patients attended in the emergency department. Stroke recurrence, myocardial infarction, or any vascular event was recorded at follow-up (mean of 389 days). Results-A total of 27 (32.5%) patients revealed focal abnormalities on DWI, whereas 37(44.6%) had symptoms lasting Ͼ1 hour. Large-artery disease was detected in 37 (44.6%) patients. Twenty (24.1%) patients experienced an endpoint: 2 (2.4%) myocardial infarctions, 16 (19.3%) cerebral ischemic events, and 2 cases (2.4%) of peripheral arterial disease. Cox proportional hazards multivariate analyses identified the association of symptoms Ͼ1 hour with DWI abnormalities as independent predictors of further cerebral ischemic events or any vascular event (hazard ratio [HR], 5.02; CI, 1.37 to 18.30; Pϭ0.015; and HR, 3.77; CI, 1.09 to 13.00; Pϭ0.029). Large-artery occlusive disease also remained an independent predictor of both endpoints (HR, 4.22; CI, 1.17 to 15.22; Pϭ0.028; and HR, 3.60; CI, 1.14 to 11.39; Pϭ0.0293). Conclusions-TIA patients with DWI abnormalities associated with duration of symptoms Ͼ1 hour and those with large-artery occlusive disease have a higher risk of further vascular events. Routine use of DWI and Doppler ultrasonographic examinations will be useful for identifying TIA patients at high risk to plan aggressive prevention therapies.

Collateral damage may occur in epilepsy management during the coronavirus (COVID-19) pandemic. We aimed to establish the impact of this pandemic on epilepsy patients in terms of patient-reported seizure control and emerging symptoms. Materials & Methods: This is a cross-sectional study including consecutive patients assessed by telephone contact in an epilepsy clinic during the first month of confinement. Demographic and clinical characteristics were recorded, and a 19-item questionnaire was systematically completed. Data regarding the impact of confinement, economic effects of the pandemic, and subjective perception of telemedicine were recorded. Additional clinical data were obtained in patients with a COVID-19 diagnosis. Results: Two hundred and fifty-five patients were recruited: mean age 48.2 ± 19.8 years, 121 (47.5%) women. An increase in seizure frequency was reported by 25 (9.8%) patients. Sixty-eight (26.7%) patients reported confinement-related anxiety, 22 (8.6%) depression, 31 (12.2%) both, and 72 (28.2%) insomnia. Seventythree (28.6%) patients reported a reduction in economic income. Logistic regression analysis showed that tumor-related epilepsy etiology [OR = 7.36 (95% CI 2.17-24.96)], drug-resistant epilepsy [OR = 3.44 (95% CI 1.19-9.95)], insomnia [OR = 3.25 (95% CI 1.18-8.96)], fear of epilepsy [OR = 3.26 (95% CI 1.09-9.74)], and income reduction [OR = 3.65 (95% CI 1.21-10.95)] were associated with a higher risk of increased seizure frequency. Telemedicine was considered satisfactory by 214 (83.9%) patients. Five patients were diagnosed with COVID-19, with no changes in seizure frequency. Conclusions: The COVID-19 pandemic has effects in epilepsy patients. Patients with tumor-related, drug-resistant epilepsy, insomnia, and economic difficulties are at a higher risk of increased seizure frequency. Telemedicine represents a suitable tool in this setting.

High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings are consistent with the hypothesis that inflammation may be involved in the progression and complication of intracranial large-artery occlusive disease.