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.

Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short- and long-term outcome.

Background and Purpose-Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes. Methods-Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity. Results-Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (PϽ0.0001 and Pϭ0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (Pϭ0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas. Conclusions-Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema. (Stroke.

Objective To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. Methods This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. Results Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache ( p = 0.010). Conclusions Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia.

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-In animal models of cerebral ischemia, matrix metalloproteinase (MMP) expression was significantly increased and related to blood-brain barrier disruption, edema formation, and hemorrhagic transformation (HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasminogen activator-treated animals. We aimed to determine the relationship between MMPs and HT after human ischemic stroke. Methods-Serial MMP-2 and MMP-9 determinations were performed by means of ELISA in 39 cardioembolic strokes in the middle cerebral artery territory. Hemorrhagic events were classified according to clinical and CT criteria (hemorrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated on CT at 48 hours (early HT) and again between day 5 and 7 (late HT). Results-HT was present in 41% of the patients (43.75% early HI, 25% early PH and 31.25% late HI). MMP-2 values were within normal range and were unrelated to HT. Increased expression of MMP-9 (normal range Ͻ97 ng/mL) was found among patients with and without HT (159.3Ϯ82 versus 143.9Ϯ112.6 ng/mL; Pϭ0.64). According to HT subtypes, the highest baseline MMP-9 levels corresponded to patients with late HI (240.4Ϯ111.2 versus 102.5Ϯ76.7 ng/mL for all other patients, Pϭ0.002). Baseline MMP-9 was the only variable associated with late HI in the multiple logistic regression model (OR 9; CI 1.46, 55.24; Pϭ0.010). Peak of MMP-9 at the 24-hour time point (250.6 ng/mL) was found before appearance of PH. Conclusions-MMPs are involved in some subtypes of HT after human cardioembolic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak precedes early PH. Key Words: cerebral ischemia Ⅲ embolism, cerebral Ⅲ hematoma, parenchymal Ⅲ hemorrhagic stroke Ⅲ matrix metalloproteinase H emorrhagic transformation (HT) is a feared event that may follow ischemic stroke. Thrombolytic therapy has been shown to be beneficial for acute stroke, although this therapy increases risk of HT. 1 Therefore, identification of the underlying mechanisms of this complication is critical to improvement of the safety profile of thrombolytic agents for stroke treatment.Matrix metalloproteinases (MMPs) belong to a family of zinc-binding proteolytic enzymes that normally remodel the extracellular matrix. 2 MMP-2 and MMP-9 specifically attack type IV collagen, laminin, and fibronectin, the major components of the basal lamina around cerebral blood vessels. 3 In animal models of cerebral ischemia, MMP expression was increased significantly and related to blood-brain barrier disruption, edema formation, and HT. 4,5 However, whether HT in humans also is related to MMP action remains unknown.We hypothesize that after MMPs degrade ECM components of the basal lamina, blood elements may extravasate, which leads to HT. In the present exploratory study, we aimed to correlate the expression of MMPs after human cardioembolic stroke with the appearance of different subtypes of HT. Subjects and Methods Study PopulationFrom June 1999 through March 2000, we studied prospectively consecut...

Background and Purpose-Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2 and MMP-9 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume. Methods-Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory by means of enzyme-linked immunosorbent assay. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 12, 24, and 48 hours after stroke onset. Infarct volume was measured with CT scanning at 48 hours. Results-No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHSS score (rϭ0.486, Pϭ0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% CI 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive predictive value of 94.4% to assess a patient's NIHSS (Ͻ8 or Ն8) by the end of the study.

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