Paolo Milia

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

Dysphagia following Stroke

Background: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. Methods: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. Results: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). Conclusions: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.

Outcome in Patients with Stroke Associated with Internal Carotid Artery Occlusion

Background: The clinical outcome in patients with stroke associated with internal carotid artery (ICA) occlusion is poor, although a minority may recover without dependency. The purposes of this study were (1) to assess the predictive factors of adverse outcome in patients with stroke associated with an occlusion of the ICA and (2) to evaluate the rate of spontaneous recanalization of an occluded ICA. Methods: A total of 177 consecutive patients with first-ever ischemic stroke associated with ICA occlusion were prospectively examined from the Perugia Stroke Registry. Mean age was 71.4 ± 14.3 years; 53% were males. Multiple regression models were used to analyze predictors of mortality, dependency and ipsilateral stroke recurrence. Results: The most probable cause of occlusion was atherosclerosis in 65%, cardioembolism in 22%, dissection in 9% and other causes in 4%. Thirty percent of the patients died within 30 days. After a mean follow-up of 420 days (range 1–1,970 days), 45% of the patients had died and 75% had died or were disabled. Another 6% of the patients had a recurrent stroke ipsilateral to the occluded carotid artery. Age was the only predictor of 30-day mortality (77.7 ± 9.7 vs. 68.7 ± 15.2 years; p = 0.03) and of long-term mortality or disability (p < 0.003). Hypertension (OR 0.42; 95% CI 0.17–1.00; p = 0.05) was associated with a better outcome within 30 days from stroke onset. Previous ipsilateral transient ischemic attack (OR 0.24; 95% CI 0.06–0.89; p = 0.03) and hyperlipidemia (OR 0.38; 95% CI 0.15–0.99; p = 0.049) were predictors of a better outcome with respect to long-term mortality or disability. No predictors of ipsilateral stroke recurrence were found. One hundred and five out of 177 patients had adequate follow-up ultrasound data. After a mean follow-up of 1.8 years, 10 patients had recanalization of the occluded ICA (2/71 atherosclerosis, 3/19 cardioembolism and 5/15 dissection). Conclusions: After a mean follow-up of 1.2 years, 45% of the patients with stroke associated with ICA occlusion had died, while 75% had died or were functionally dependent. The presence of either previous ipsilateral transient ischemic attack, hypertension or hyperlipidemia was associated with a favorable outcome. Recanalization of an occluded ICA occurred in a minority of patients and it was associated with cardioembolism and with arterial dissection.

Recanalization of Cervical Artery Dissection: Influencing Factors and Role in Neurological Outcome

Background and Purpose: Generally, the prognosis for cervical artery dissection (CAD) is uncertain. The recanalization rate of CAD can be up to 85% within 3 months. This study evaluates the variables that might affect recanalization and the role of recanalization as a predictor for neurological outcome. Patients and Results: This study prospectively included 38 patients with acute stroke following occlusion due to CAD (18 males, 20 females, median age 50.5 years, range 16–82). Vertebral and carotid dissections were equally distributed (19 carotid dissections). The recanalization rate was influenced by the presence of hypertension (p = 0.001). Outcomes were dependent on infarct location. Patients with lateral medullary infarction returned to functional independence (p = 0.026), while patients with deep hemispheric infarction tended to have a disabling stroke (p = 0.068). The presence of good collaterals seemed to influence functional independence (p = 0.03). Conclusion: There seemed to be no relationship between outcome and the rate of recanalization following CAD. Recanalization appeared to be a spontaneous mechanism, which could have depended on the intrinsic condition of the vessels. Finally, neurological outcome was dependent on lesion localization and the presence of good collaterals.

Atrial fibrillation in patients with first-ever stroke: frequency, antithrombotic treatment before the event and effect on clinical outcome

Summary.  Background and purposes: Atrial fibrillation (AF) is an independent risk factor for stroke. The aims of this study were to assess: (i) the frequency of known or unknown AF in patients admitted to the hospital for a first‐ever ischemic stroke and whether AF is associated with an adverse outcome at discharge (death or disability); (ii) the rates and determinants for the use of antithrombotic agents before stroke in patients with known AF and the adherence to the current treatment guidelines; and (iii) whether the lack of adherence to the current guidelines is associated with adverse outcome at discharge. Methods: Consecutive patients with acute first‐ever stroke admitted to an individual Stroke Unit between January 2000 to December 2003, were included in the study. Twelve‐lead electrocardiogram (ECG) was performed in all patients on admission. Functional outcome was measured at discharge according to modified Rankin Score. Results: A total of 1549 patients were included in the study: 238 patients (15.4%) were known to have AF and 76 (4.9%) were diagnosed with AF (unknown) on ECG performed on admission. At discharge 91 patients (5.9%) had died and 605 patients (39.0%) had died or were functionally dependent. Multivariate analysis showed that AF on admission was correlated with mortality or disability (OR = 1.58, 95% CI 1.09–2.30, P = 0.015). Before stroke, 124 out of 238 patients with known AF (52.1%) were not on antithrombotic therapy, 83 (34.9%) were receiving antiplatelet and 31 (13.0%) anticoagulant treatment. Previous transient ischemic attack, history of ischemic heart disease and hyperlipidemia were associated with the use of antithrombotic therapy. Only 24 out of 114 patients on antithrombotic treatment on admission were adequately treated according to the current guidelines. Of the adequately treated patients, 41.7% died or were disabled at discharge respect to 52.3% of the patients non‐adequately treated (RR = 0.80, 95% CI 0.48–1.30). Conclusions: AF (on history or new diagnosis) was present in 20.3% of the patients with first‐ever stroke admitted to a Stroke Unit and it was associated with increased mortality or disability. Only 10% of patients with known AF were previously receiving an adequate antithrombotic treatment according to current guidelines.

Neurovascular territory involved in different etiological subtypes of ischemic stroke in the Perugia Stroke Registry.

We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first‐ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1719 patients were evaluated: 1284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). In conclusion: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two‐thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa.

Is ultrasound examination sufficient in the evaluation of patients with internal carotid artery severe stenosis or occlusion

Background and Purpose: Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade internal carotid artery (ICA) stenosis. Some authors have suggested that when ultrasound shows a stenosis 70–99%, CE can be performed without further imaging study. However, ultrasound findings that suggest an ICA occlusion, not confirmed by angiography but which instead show a near-occlusion usually benefit from CE. The objectives of this study are: (1) to evaluate how angiography-obtained information on intracranial arteries affects the treatment decision in patients with 70–99% ICA stenosis, and (2) to evaluate when a symptomatic ICA occlusion shown by ultrasound could actually be a patent artery and therefore benefit from CE. Materials and Methods: We prospectively collected the cerebral angiograms of 133 consecutive patients with TIA or non-disabling stroke due to large artery disease where ultrasound suggested a stenosis ≧70% or occlusion of symptomatic ICA; we calculated the frequency of intracranial vascular malformations and intracranial artery disease (IAD) located in the infraclinoid or supraclinoid portion of the ICA, and in the anterior or middle cerebral artery. Results: Ultrasound showed 31 ICA occlusions and 102 ICA with 70–99% stenosis. All the patients with an ICA stenosis 70–99% on ultrasound examination had the degree of stenosis confirmed by angiography. Two out of 31 patients did not have a complete occlusion but angiography showed a near-occlusion and consequently they underwent CE. Sixty-five (62.5%) out of 104 patients with patent ICA had IAD (mild 26.9%, moderate 21.2%, and severe 14.4%). Five patients (4.8%) had intracranial vascular malformations (4 aneurysms and 1 arteriovenous malformation). One patient had disabling stroke during angiography. Seven patients (6.7%) did not undergo CE after angiography (1 patient had an aneurysm >10 mm, 1 patient had a very tight stenosis of the basilar artery, 5 patients had intracranial stenosis more severe than the extracranial stenosis). Conclusions: In patients that on the basis of ultrasound examination can benefit from CE, information on intracranial arteries is necessary. Moreover, complete occlusion cannot be detected with certainty only by ultrasound examination.

THE PERUGIA HOSPITAL-BASED STROKE REGISTRY: REPORT OF THE 2ND YEAR

This study reports the characteristics of stroke patients admitted to our hospital in the period Jan 1st, 1998–Dec 31st 1999. Seven hundred and ninety seven consecutive subjects (412 males; mean age 71 ± 13 years) with a first-ever stroke were registered. Two-thirds of patients (65%) were admitted to the Stroke Unit (SU). The remaining part was managed in six general medicine wards (GM) or other services [neurosurgery and intensive care units (ICU+NS)]. Ischemic stroke occurred in 534 subjects (67%). The high prevalence (30.1%) of haemorrhages can be partly explained by the presence of specialized neurosurgical services. Athero-thrombotic infarctions occurred in 21.7% of patients, lacunar in 24.7%, cardioembolic in 18.1%, other determined in 6.1%, and other undetermined in 27.5%. Overall hospital mortality was 10%. In cerebral hemorrhage mortality was 18% (44/240) vs. 6.3% (32/534) in ischemic stroke (p<0.05). The distribution of stroke types and mortality was similar to other previous reports.

Effect of on-admission antiplatelet treatment on patients with cerebral hemorrhage.

Background: Antiplatelet treatment remains the first choice for primary and secondary prevention of vascular diseases; even so, expected benefits may be offset by risk of bleeding, particularly cerebral hemorrhage. The aim of this study was to assess the influence of antiplatelet treatment on clinical outcome at hospital discharge. Materials and Methods: Consecutive patients with first-ever stroke due to a primary intraparenchymal hemorrhage were prospectively identified over a 4-year period (2000–2003). Data on hemorrhage location, vascular risk factors, and antiplatelet and anticoagulant treatment were collected. At discharge, outcome was measured using the modified Rankin Scale (disabling stroke ≧3). Patients treated with anticoagulant therapy were excluded from the study. Results: Of 457 consecutive patients with cerebral hemorrhage, 94 (20.5%) had been taking antiplatelet agents. The treated patients (mean age for antiplatelet group 78.9 ± 9.0 years) were older than the nontreated patients (73.8 ± 9.4, p = 0.02). In-hospital mortality was 23.4 and 23.1% (p = n.s.) for patients who had been taking antiplatelet agents or no treatment. Poor outcome at discharge was found in 52.1 and 59.7% (p = n.s.), respectively. Univariate analysis showed that age and coma at admission were predictors of disability at discharge, but antiplatelet treatment was not. Additionally, age and coma were shown to be determinants of disability at discharge after multivariate analysis: OR 1.03 per year (95% CI: 1.018–1.049), p < 0.001 and OR 1.68 (95% CI: 1.138–2.503), p = 0.009, respectively. Conclusions: Hemorrhagic stroke continues to be responsible for a high percentage of disability and death. Furthermore, it was seen here that functional outcome was independent of previous antiplatelet treatment.

Admission leukocytosis in acute cerebral ischemia: influence on early outcome.

BACKGROUND Leukocytes are the first cells that arrive in the stroke region(s), and they increase in peripheral blood. The contribution or leukocytes in the early acute phase of cerebral ischemia has not yet been investigated. METHODS In consecutive first-ever acute ischemic stroke patients whose symptoms had started <12 hours earlier, we aimed to establish whether admission leukocyte count affects the short-term neurologic outcome, and whether there are differences between the various clinical syndromes of stroke. The National Institutes of Health Stroke Scale (NIHSS) was assessed at admission (NIHSS(0)) and after 72 hours (NIHSS(72)). Modified Rankin scale (mRS) scores were evaluated at discharge. The Spearman rank correlation was used for the correlation between leukocytes and outcome measures. RESULTS Eight hundred and eleven patients were included (median age 77 years [range 68-82]; 418 [53%] were male; the median NIHSS(0) score was 7 [range 4-12], the median NIHSS(72) score was 6 [range 3-12], and the median mRS score was 2 [range 2-4]). The median leukocyte count at admission was 8100/mm(3) (range 6500-10300). Higher leukocyte levels predicted a worst clinical presentation and a poor functional outcome (NIHSS(0)P < .001; NIHSS(72)P < .001; mRS P < .001). The correlation between leukocyte count and outcome measures remained significant after multivariate analysis (NIHSS(0)P < .001; NIHSS(72)P < .001; mRS P < .008). Focusing on clinical syndromes, a higher leukocyte count predicted severe NIHSS(0) and NIHSS(72) scores in patients with total anterior cerebral stroke (P = .001), partial anterior cerebral stroke (P = .004), or posterior cerebral stroke (P = .026). CONCLUSIONS An elevated leukocyte count in the acute phase of cerebral ischemia is a significant independent predictor of poor initial stroke severity, poor clinical outcome after 72 hours, and discharge disability. The involved underlying mechanism is still to determined.