Vanessa Palumbo

Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging.

We examined whether the presence of diffusion‐weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤ 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90‐day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90‐day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence. Ann Neurol 2005;57:848–854

Leukoaraiosis and intracerebral hemorrhage after thrombolysis in acute stroke.

Objectives: To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA). Methods: Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome. Results: An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both. Conclusion: The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

Postmortem Examination of Vascular Lesions in Cognitive Impairment. A Survey Among Neuropathological Services

Background and Purpose— A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients. Methods— Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed. Results— A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline. Conclusions— The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment.

Progressive lacunar stroke: review of mechanisms, prognostic features, and putative treatments.

Lacunar stroke is generally considered to have a fair outcome. However 20–30% of patients with lacunar stroke worsen neurologically in hours or days after onset, reaching eventually an unexpectedly severe disability status. In the field of acute stroke, progressive lacunar stroke remains an important unresolved practice problem, because as yet no treatment does exist proven to prevent or halt progression. Pathophysiology of progression is yet incompletely understood. Hemodynamic factors, extension of thrombosis, excitotoxicity, and inflammation, have been proposed as possible mechanisms of progression. A few clinical studies also aimed at establishing presentation features that may help identifying patients at risk of deterioration. In this paper, we review hypothesized mechanisms of lacunar stroke progression and possible markers of early deterioration. Moreover, based on putative mechanisms and suggestions from reported evidence, we propose a few treatments that seem worthy to be tested by randomized clinical trials.

MMP9 Variation After Thrombolysis Is Associated With Hemorrhagic Transformation of Lesion and Death

Background and Purpose— Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods— We measured MMPs 1, 2, 3, 7, 8, 9, and tissue inhibitors of metalloproteinases 1, 2, 4 circulating level in blood taken before and 24 hours after tPA from 327 patients (mean age, 68.9±12.1 years; median National Institutes of Health Stroke Scale, 11) with acute ischemic stroke. Delta median values ([24 hours post tPA–pre tPA]/pre tPA) of each MMP or tissue inhibitors of metalloproteinase were analyzed across subgroups of patients undergoing symptomatic intracerebral hemorrhage, 3-month death, or 3-month modified Rankin Scale score 3 to 6. Results— Adjusting for major clinical determinants, only matrix metalloproteinase-9 variation proved independently associated with death (odds ratio [95% confidence interval], 1.58 [1.11–2.26]; P=0.045) or symptomatic intracerebral hemorrhage (odds ratio [95% confidence interval], 1.40 [1.02–1.92]; P=0.049). Both matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 changes were correlated with baseline, 24 hours, and 7 days National Institutes of Health Stroke Scale (Spearman P from <0.001 to 0.040). Conclusions— Our clinical evidence corroborates the detrimental role of matrix metalloproteinase-9 during ischemic stroke treated with thrombolysis, and prompts clinical trials testing agents antagonizing its effects.

The Safety and Efficacy of Thrombolysis for Strokes After Cardiac Catheterization

OBJECTIVES The purpose of this study was to systematically compare clinical outcomes of patients treated with thrombolysis with those without treatment in a multi-year, multicenter cohort of strokes after cardiac catheterization. BACKGROUND Ischemic strokes after cardiac catheterization procedures, although uncommon, lead to the morbidity and mortality of thousands of patients each year. Despite the availability of Food and Drug Administration-approved thrombolytic therapy for acute ischemic stroke since 1996, thrombolysis remains unestablished in the setting of cardiac catheterization, owing to unique concerns regarding safety and efficacy. METHODS Consecutive cases of ischemic stroke after cardiac catheterization were abstracted retrospectively and reviewed by clinicians at 7 major North American academic centers with acute stroke teams. Safety and efficacy outcome measures were pre-defined. RESULTS A total of 66 cases of ischemic strokes after cardiac catheterization were identified over 3 to 4 years; 12 (18%) were treated with thrombolysis, consisting of 7 intravenous and 5 intra-arterial recombinant tissue plasminogen activator cases. Improvement in stroke symptoms, as measured by the primary efficacy measure of median change in National Institutes of Health Stroke Scale score from baseline to 24 h, was greater in treated versus nontreated cases (p < 0.001). Additional secondary measures of efficacy also showed better outcomes in the treated group. There were no significant differences in bleeding events, defined as symptomatic intracerebral hemorrhage, hemopericardium, or other systemic bleeding resulting in hemodynamic instability or blood transfusions. Mortality rates were also similar. CONCLUSIONS Thrombolysis might improve early outcomes after post-catheterization strokes and seems safe in this context. Emergent cerebral revascularization should be a routine consideration.

Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis

Objective: To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome. Methods: We included studies of patients with acute ischemic stroke, treated with IV or intra-arterial thrombolysis, which assessed functional outcome (3-month modified Rankin Scale [mRS]) or sICH in relation to leukoaraiosis on pretreatment neuroimaging (CT or MRI). We used random-effects models to calculate pooled relative risks (RR) of sICH and poor functional outcome (mRS ≥ 2) for any vs no leukoaraiosis (using any rating scale) and for no to mild vs moderate to severe leukoaraiosis (using the Van Swieten or Fazekas Schmidt scale). Results: We identified 15 studies (total n = 6,967). For sICH outcome, the RR was 1.65 (n = 5,551; 95% confidence interval [CI] 1.26–2.16, p = 0.001) with an absolute risk (AR) increase of 2.5% for any leukoaraiosis vs none. The RR was 2.4 (n = 4,192; 95% CI 1.83–3.14, p = 0.001) with an AR increase of 6.2% for moderate to severe vs no to mild leukoaraiosis. For poor functional outcome; the RR was 1.30 (n = 3,401; 95% CI 1.19–1.42, p = 0.001) with an AR increase of 15.4% for any leukoaraiosis vs none. The RR was 1.31 (n = 3,659; 95% CI 1.22–1.42, p = 0.001) with an AR increase of 17.5% for moderate to severe vs no to mild leukoaraiosis. No statistical heterogeneity was noted for any of the analyses. Conclusions: Leukoaraiosis presence and severity are consistently associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke.

Combined full‐dose IV and endovascular thrombolysis in acute ischaemic stroke

Background There is an increasing trend to treating proximal vessel occlusions with intravenous–inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy. Methods Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2–3 flow on angiography. Results Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27–0·84) and favourable outcome (RR 2·14 confidence interval95 1·3–3·5). Conclusions Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified.

Pathological Lesions in Vascular Dementia

Abstract: According to current diagnostic criteria, a definite diagnosis of vascular dementia (VaD) can be reached on pathological grounds by showing the presence of vascular lesions and the absence of degenerative changes exceeding those expected for age. However, while it is commonly accepted that VaD is a group of heterogeneous entities rather than a process with a unique pathological substrate, the spectrum of vessel and parenchyma changes etiologically associated with the clinical syndrome remains basically unidentified. The review of some recent clinical‐pathological series shows that different studies have assessed the presence of dissimilar vascular lesions and that, in many cases, no pathological definition was given. This has hindered the clarification of clinical‐pathological correlations in the field of VaD. In this scenario, the use of animal models of cerebrovascular diseases may help to elucidate the type of lesions possibly linked with cognitive impairment in humans and might provide insight into some of the pathophysiological mechanisms of vascular cognitive impairment. A consensus is today needed in order to harmonize the pathological examination of vascular lesions in cases of dementia. An ongoing survey aimed at collecting information about the procedures used in different pathological laboratories in the assessment of lesions possibly associated with dementia is finally presented.

Leukoaraiosis and lacunes are associated with poor clinical outcomes in ischemic stroke patients treated with intravenous thrombolysis.

Background The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood. Aim We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis. Methods We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes. We dichotomized the burden of small vessel disease to “absent or moderate” and “severe.” Clinical outcomes at 90 days included excellent outcome (mRS = 0–1), good outcome (mRS = 0–2), and the occurrence of symptomatic intracerebral hemorrhage. Sensitivity analysis was performed on two age groups (≤80 versus >80). We ran logistic regression adjusting for confounders to evaluate independent effect of small vessel disease on outcomes. Results There were 820 patients with available brain computer tomography with mean age (±SD) of 71.3 (±13.2), 455 (55.5%) were male. Of these, 123 (15%) patients had severe small vessel disease at baseline. Age group analysis revealed significant associations of small vessel disease only in patients aged ≤80. After adjustment for confounders, presence of severe small vessel disease reduced the chances of both excellent (OR = 0.42, 95% CI = 0.24–0.74) and good outcome (OR = 0.35, 95% CI = 0.21–0.58) and with an increased risk of symptomatic intracerebral hemorrhage (OR = 5.91; 95% CI = 2.40–14.57). Conclusion When considered together as radiological expressions of small vessel disease, presence and severity of severe leukoaraiosis and lacunes on baseline computer tomography scan are associated with poor clinical outcomes in patients treated with i.v. thrombolysis.